bromochloroacetic-acid and Adenoma

Most pituitary region masses are pituitary adenomas; however, when other sellar region masses are encountered by clinicians or pathologists, the differential diagnosis can be broad. This review will focus on updates for pituitary adenomas, as well as briefly discuss some of these other entities: Rathke cleft cyst, hypophysitis, craniopharyngioma, pituicytoma, and spindle cell oncocytoma.. The use of new immunohistochemical (IHC) tools for assessing transcription factors, pituitary transcription factor-1, steroidogenic factor-1, and the not-yet-widely available Tpit IHC have provided insights into origin particularly of clinically silent and even hormone-negative pituitary adenomas. IHC for keratins coupled with use of E-cadherin IHC can serve to easily identify sparsely granulated growth hormone adenomas that behave more aggressively and may not respond well to some therapies. Thyroid transcription factor-1 IHC has shown common embryological lineage of pituicytoma, spindle cell oncocytoma, and granular cell tumor of neurohypophysis.. IHC supplements classification of pituitary adenoma subtypes for clinicians and can confirm diagnosis of nonpituitary adenoma sellar region masses.

Topics: Adenoma; Antigens, CD; Cadherins; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Pituitary Gland; Pituitary Neoplasms; Steroidogenic Factor 1; Thyroid Nuclear Factor 1; Transcription Factors

There is a lack of a comprehensive immunohistochemical (IHC) analysis of canalicular adenoma (CanAd), especially when combined with a description of the unique histologic features. Given the usual small biopsies, IHC may be useful in distinguishing CanAd from other tumors in the differential diagnosis. Retrospective. The patients included 54 females and 13 males (4.2:1), aged 43-90 years, with a mean age at presentation of 69.9 years. Clinical presentation was generally a mass (n = 61) slowly increasing in size (mean 38.5 months), affecting the upper lip (n = 46), buccal mucosa (n = 17) or palate (n = 4), involving the right (n = 29), left (n = 24) or midline (n = 9), without any major salivary gland tumors. The tumors ranged in size from 0.2 to 3 cm (mean 1.2 cm). Most tumors were multilobular or bosselated (76 %), often surrounded by a capsule. Histologically, the tumors were characterized by cystic spaces, tumor cords with beading, tubule formation, and by the presence of luminal squamous balls (n = 41). The cells were cuboidal to columnar with stippled chromatin. Mitoses were inconspicuous. A myxoid stroma (n = 64), sclerosis (n = 42), luminal hemorrhage (n = 51), and luminal microliths (calcifications) (n = 33) were characteristic. Nine (13.4 %) were multifocal. CanAd showed the following characteristic immunohistochemistry findings: CK-pan and S100 protein (strong, diffuse reaction); peripheral or luminal GFAP reaction; CK5/6 and p16 luminal squamous ball reaction; SOX10 nuclear reaction; cytoplasmic p63 reaction. CanAd are unique minor salivary gland tumors showing a distinct architecture and phenotype. They predilect to older women, with the majority multilobulated and affecting the upper lip, multifocal in 13 %; no major salivary gland tumors were identified. S100 protein, CK-pan, GFAP and SOX10 are positive, with luminal squamous balls highlighted by CK5/6 or p16.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biopsy; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; SOXE Transcription Factors

Metanephric adenoma (MA) is a rare, benign renal tumor that can be found in individuals of any age. The histological features of this lesion are well known; however, cytological features of this entity have rarely been described. Herein, we present the case of a 37-year-old white woman with multiple endocrine dysfunctions and a renal mass. The diagnosis of metanephric adenoma was suggested as a differential diagnosis during imprint cytology; this diagnosis was later confirmed by core needle biopsy (CNB) and the results of immunostaining. To our knowledge, this is the first time in the literature that the diagnosis of metanephric adenoma was initially suggested on imprint cytologic testing of a CNB. We review the literature regarding the cytologic features and immunohistochemical reactivity of this tumor to raise awareness of this entity among pathologists and to distinguish it from other lesions, such as renal-cell carcinoma, so physicians can use this information to help them avoid calling for an unnecessary radical nephrectomy.

Topics: Adenoma; Adult; CD57 Antigens; Diagnosis, Differential; Female; Humans; Keratins; Kidney; Kidney Neoplasms

To investigate for the first time the immunohistochemical and mutational status of β-catenin in a mandibular case of adenomatoid odontogenic tumor (AOT) and to review the immunohistochemical expression data of various markers (cytokeratins, metalloproteinases, etc) in such a lesion.. A case of follicular-type AOT in a young male patient was analyzed in regard to the immunohistochemical expression of β-catenin and mutations of the β-catenin gene (CTNNB1). Its expression is altered in some odontogenic tumors.. We found a strong cytoplasmic expression of β-catenin, but no molecular anomaly within the exon 3 of CTNNB1. β-catenin is considered to play a role in cell differentiation processes.. Our results were consistent with previous findings in ameloblastoma and malignant odontogenic tumors. However, β-catenin alterations had not been explored in AOT so far. Further studies are necessary to understand the specific regulation of β-catenin in the AOT pathogenesis.

Topics: Adenoma; Adolescent; beta Catenin; Cadherins; DNA Mutational Analysis; Extracellular Matrix Proteins; Humans; Keratins; Male; Mandibular Neoplasms; Matrix Metalloproteinases; Odontogenic Tumors

Primary spindle cell neoplasms of the thyroid gland are quite rare. They encompass a heterogeneous group of benign and malignant lesions of mesenchymal and epithelial origin. We herein describe two unusual follicular thyroid adenomas dominated by spindle cells with occasional areas of colloid-forming follicular differentiation. The tumors affected a 77-year woman and a 70-year old man; both had a long-history of monoclonal gammopathy of unknown significance (MGUS). One tumor presented as a large cold thyroid nodule and the other was an autopsy finding. The tumors were predominantly composed of fibroblast-like spindled cells. One case showed prominent meningioma-like concentric perivascular arrangement and contained cytoplasmic melanin-like pigment. Stromal hyalinization was a prominent feature of both. By immunohistochemistry, the spindled cells expressed vimentin, pankeratin (KL1), thyroglobulin and TTF1 consistent with a follicular differentiation. They did not stain with calcitonin, CEA and other lineage-specific mesenchymal, neuroendocrine and melanocytic markers. There was no evidence of metastasis at autopsy (case 2) or at last follow-up 2 years after surgery (case 1). These cases demonstrate the diversity of follicular thyroid neoplasms and the unusual occurrence of extensive spindle cell metaplasia. These uncommon lesions need to be distinguished from spindle cell medullary carcinoma, paucicellular spindle cell anaplastic carcinoma, spindle cell foci in papillary and follicular carcinoma, solitary fibrous tumor and other rare benign and malignant mesenchymal lesions.

Topics: Adenoma; Aged; Biomarkers, Tumor; DNA-Binding Proteins; Fatal Outcome; Female; Humans; Keratins; Male; Monoclonal Gammopathy of Undetermined Significance; Thyroglobulin; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy; Transcription Factors; Vimentin

To investigate the clinicopathological and immunohistochemical features, diagnosis and differential diagnosis of nipple adenoma of the breast.. Morphological observation and immunohistochemistry were applied to 18 cases of nipple adenoma with a review of the related literatures.. The neoplasms were localized at nipples or under the areola of breast, adherent to the epidermis, mainly composed of dilated ducts in a tubular appearance associated with fibrotic matrix. The glandular epithelium showed various type of proliferation, forming thick layers or complex structures such as papillae, micropapillae, tufts, fronds, arcades or bridges accompanying with solid or cribriform cell nests. The tumor cells were crowding, lack of an uniform morphology and polarity with intact myoepithelial cells around the ducts. By immunostaining, the glandular epithelium was diffusely positive for 34betaE12, patchily positive for CK5/6, and negative for p53 and c-erbB-2. The myoepithelium, positive for p63, smooth muscle actin and Calponin, was well preserved and outlining the ducts.. Nipple adenoma is an infrequent type of benign breast neoplasm, presenting as sclerosing papilloma, papillomatosis or florid sclerosing adenosis. It is easily confused with atypical ductal hyperplasia/low grade ductal carcinoma in situ, invasive ductal carcinoma or low grade adenosquamous carcinoma. A correct diagnosis is based on the peculiar location and morphology of the tumor, and immunohistochemistry is helpful in some cases.

Topics: Adenoma; Adult; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Adenosquamous; Carcinoma, Ductal, Breast; Diagnosis, Differential; Female; Humans; Keratin-5; Keratins; Middle Aged; Nipples

The precise diagnosis of follicular thyroid lesions is frequently debated because of the subjective nature of capsular invasion as well as both the histological and cytological characteristics. Furthermore, several different prognostic indices have been devised to examine prognosis associated with thyroid cancer. Herein, we describe how these confounding elements can affect the ability to accurately predict prognosis for patients with follicular thyroid lesions.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Galectin 3; Humans; Keratins; Lymphatic Metastasis; Neoplasm Invasiveness; Prognosis; Thyroid Neoplasms

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.

Topics: Adenocarcinoma; Adenoma; Ampulla of Vater; Common Bile Duct Neoplasms; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin 5AC; Mucin-2; Mucins; Prognosis

A 1 cm polypoid lesion was encountered on the posterior vaginal wall in a 56-year-old woman with no history of diethylstilbestrol exposure that on microscopic examination was a moderately differentiated adenocarcinoma of intestinal type. The tumor was cytokeratin 20 and carcinoembryonic antigen positive and negative for cytokeratin 7. Mucin histochemistry demonstrated the presence of o-acetylated sialomucin, a specific marker of large intestinal differentiation. The initial interpretation favored a metastasis from a colonic adenocarcinoma, but clinical investigations showed no evidence of a primary gastrointestinal lesion. The morphology, histochemical, and differential cytokeratin profile led to the lesion being reinterpreted as a primary intestinal-type adenocarcinoma of the vagina arising from a tubular adenoma. Although a very rare tumor, awareness of this lesion is important as it must be distinguished from metastatic adenocarcinomas from other sites.

Topics: Adenocarcinoma; Adenoma; Carcinoembryonic Antigen; Fallopian Tubes; Female; Humans; Intestinal Neoplasms; Keratins; Middle Aged; Mucins; Omentum; Ovariectomy; Vaginal Neoplasms

Pituitary carcinomas, currently defined as primary adenohypophyseal neoplasms with evidence of either brain invasion or metastatic spread, are exceptionally rare. A case of corticotroph pituitary carcinoma is reported. A 17-year-old female first presented with an invasive and clinically non-functioning pituitary macroadenoma. The primary pituitary lesion lacked atypical histological features and retrospective immunohistochemical studies confirmed its corticotrophic nature. Repeated episodes of local recurrence followed together with the acquisition of severe Cushing's disease. Local disease control was not obtained despite repeated surgical decompression and courses of radiation therapy. Systemic dissemination with multiple bone metastases became manifest eleven years after the first presentation. Atypical histological features and Crooke's hyaline change were evident in both the recurrent and metastatic disease. She remains alive at last follow-up with severe complications relating to persisting sellar and metastatic disease and ongoing endocrine dysfunction. A further 32 cases of pituitary corticotroph carcinoma reported in English are reviewed to highlight the clinicopathological features of this rare form of pituitary neoplasm. Difficulties associated with the diagnosis and management of pituitary carcinoma are also discussed.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Cushing Syndrome; Female; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pituitary Gland, Anterior; Pituitary Neoplasms

Developmentally pathological conditions of the anterior pituitary cells include failed separation of the primary pituitary gland into sellar and pharyngeal ones, ectopic migration into the subarachnoid space, and basophil invasion into the posterior lobe although the last is a physiological phenomenon with pathological potentiality in certain circumstances. Pituitary primordium appears at about 4 weeks of gestation. One of the causes of the pituitary gland agenesis may be a formation of the primary hypothalamic ganglionic hamartoma just at the time of occurrence of the pituitary primordium, as analyzed in cases of Pallister-Hall syndrome. A double pituitary in a single individual is a rare malformation. Its pathogenesis is considered as a result of notochordal anomaly. In the 8th gestational week, the primary pituitary gland separates into sellar and pharyngeal parts. The disturbance of this histogenesis results in a rare pituitary malformation, a "pharyngosellar pituitary." Despite the failed separation in this case, differentiation of the pituitary cells proceeds and the hormone production of this malformed pituitary gland can be displayed immunohistochemically. In this case, the distribution of the different hormone producing cells was atypical, particularly in those of gonadotropic hormones and ACTH. Life-long existence of the pharyngeal pituitary is a normal anatomical state in humans. Cell differentiation (hormone production) in the pharyngeal pituitary occurs about 4-10 weeks later than in the sellar pituitary. In pharyngeal pituitary, all kinds of adenohypophyseal hormones are produced. Extracranial pituitary adenomas (with intact sellar pituitary), exclusively found in the nasopharynx, sphenoid sinus, and clivus, may occur from the pharyngeal pituitary while another tumorigenesis can develop from the residual tissue fragment in the craniopharyngeal canal. The "overshoot" of the adenohypophyseal cell migration in the distal part of the sellar pituitary is frequently observed in the leptomeninges of the peri-infundibular or peri-hypothalamic region as ectopic pituitary cell clusters that are apparently independent of the pars tuberalis. It is suggested that these cells, frequently found in "normal" individuals, may be one of the possible origins of the intracranial ectopic pituitary adenomas. However, the reason why a majority of the reported intracranial ectopic pituitary tumors are ACTH-adenomas remains unexplained, since the ectopic cells, found

Topics: Adenoma; Adrenocorticotropic Hormone; Basophils; Cell Movement; Choristoma; Female; Histocytochemistry; Humans; Keratins; Male; Microscopy, Electron; Pharyngeal Diseases; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Pituitary Neoplasms

Two cases of tumors of the posterior portion of the petrous bone are presented. Both resulted in significant loss of hearing and caused extensive bone destruction. Microscopically, they corresponded to papillary adenomatous tumors with few histologically aggressive features. Immunohistochemical studies were done, and a positive reaction was obtained with the antibodies against the cytokeratins, Leu-7 and neuronal-specific enolase. A diagnosis of adenocarcinoma of the endolymphatic sac was made. These are rare tumors known for their long clinical prodrome and their local aggressiveness. Increased awareness will allow for earlier diagnosis and treatment.

Topics: Adenocarcinoma; Adenoma; Adolescent; Adult; Bone Neoplasms; CD57 Antigens; Endolymphatic Sac; Female; Humans; Immunohistochemistry; Keratins; Phosphopyruvate Hydratase; Temporal Bone; Tomography, X-Ray Computed

Intercalated duct lesions (IDLs) are usually asymptomatic. We report a case of IDL, in which a palpable mass formed. The patient was a 45-year-old Japanese male, who noticed a mass in the left parotid region. The nodular lesion was well-circumscribed, but did not have a fibrous capsule or exhibit infiltrative growth. It contained a small cystic space and consisted of basaloid cells arranged in a cribriform pattern and inner ductal cells. It had some solid areas of nest-like proliferation displaying mild cellular atypia. Immunohistochemically, the luminal cells were positive for cytokeratin (CK)7 and epithelial membrane antigen, and the abluminal cells were positive for CK5/6, p63, and DOG1. S-100 protein-positive stromal cells were also seen. The lesion's cells were all positive for SOX10, and the nuclei of some basaloid cells were positive for β-catenin. The Ki-67 labeling index was 3.8%. The ductal cells contained diastase-digestion-resistant, Periodic acid Schiff-positive zymogen granules. Genetically, the lesion harbored a missense mutation in the CTNNB1 gene. We diagnosed the lesion as an IDL. As IDLs are usually small non-neoplastic lesions, symptomatic cases are rare. Based on its common immunohistochemical and genetic features, IDL may be a precursor of basal cell adenoma/adenocarcinoma, such as intercalated duct adenoma.

Topics: Adenocarcinoma; Adenoma; Amylases; beta Catenin; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin-1; Parotid Gland; Periodic Acid; S100 Proteins; Salivary Gland Neoplasms

In the Turkish saddle area, there is a wide variety of pathological processes, the vast majority of which present as tumors of various origins (up to 90%). For a clear morphological verification of the diagnosis, it is proposed to use a diagnostic algorithm that includes the stages of differential diagnosis of normal adenohypophysis and neurohypophysis with tumors in the anterior and posterior lobes of the pituitary gland, non-pituitary origin neoplasms, as well as with non-tumor pathological processes (inflammation, cystic masses, and hyperplasia). For morphological diagnosis, histochemical and immunohistochemical methods are recommended using various staining techniques (silver impregnation, periodic acid Schiff reaction) of tissue specimens and antibody panels (pituitary hormones, low-molecular cytokeratins, pituitary transcription factors, neuroendocrine markers, etc.).. В области турецкого седла наблюдается большое разнообразие патологических процессов, подавляющее большинство которых представлено опухолями различного происхождения (до 90%). Для четкой морфологической верификации диагноза предлагается использовать алгоритм диагностики, который включает этапы дифференциальной диагностики нормального адено- и нейрогипофиза с опухолями передней и задней доли гипофиза, новообразованиями негипофизарного происхождения, а также с неопухолевыми патологическими процессами (воспаление, кистозные образования, гиперплазия). Для морфологической диагностики рекомендуются гистохимические и иммуногистохимические методы с использованием разнообразных техник окраски (импрегнация серебром, ШИК-реакция) гистологических препаратов и панели антител (гормоны гипофиза, низкомолекулярные цитокератины, транскрипционные гипофизарные факторы, нейроэндокринные маркеры и др.).

Topics: Adenoma; Algorithms; Diagnosis, Differential; Humans; Keratins; Pituitary Gland; Pituitary Neoplasms

-Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined.. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use.. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas.. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2.. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Biomarkers; Cluster Analysis; Female; Growth Hormone; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Sensitivity and Specificity; Steroidogenic Factor 1; Thyrotropin; Transcription Factor Pit-1; Young Adult

Gangliocytomas originating in the sellar region are rare; most are tumors composed of gangliocytic and pituitary adenomatous elements, forming the so-called mixed gangliocytoma-pituitary adenoma. The majority of mixed gangliocytoma adenomas are associated with endocrinopathies, mainly acromegaly and less often Cushing disease and hyperprolactinemia. In the present study, 10 cases of mixed gangliocytoma and somatotroph adenomas were evaluated for patterns of cellular differentiation and expression of lineage-specific transcription factors. The tumors were characterized by immunohistochemistry for pituitary hormones, cytokeratins, Pit-1, and the neuronal markers NeuN, neurofilaments (NFP), and MAP2. Double-labeling immunohistochemistry for Pit-1/GH, Pit-1/NFP, Pit-1/MAP2, and NeuN/GH was performed in 9/10 tumors. Our data demonstrate that both adenomatous and ganglionic cells express the acidophilic lineage transcription factor Pit-1. Although mixed gangliocytomas and somatotroph adenomas show histologically distinct cellular populations, there is at least a small population of cells that coexpress the Pit-1 transcription factor and neuronal-associated cytoskeletal proteins favoring the theory of transdifferentiation of neuroendocrine cells into neuronal elements of these mixed tumors.

Topics: Adenoma; Adult; Antigens, Nuclear; Biomarkers, Tumor; Biopsy; Cell Differentiation; Cell Lineage; Female; Ganglioneuroma; Hormones; Humans; Immunohistochemistry; Keratins; Male; Microtubule-Associated Proteins; Middle Aged; Neoplasms, Complex and Mixed; Nerve Tissue Proteins; Neurofilament Proteins; Pituitary Neoplasms; Transcription Factor Pit-1

A 6-year-old female rabbit was presented to a veterinary clinic, and the result of ultrasound examination suggested a tumor in the uterine tube. Subsequently, both ovaries and uterus were surgically removed. In gross, a single large cyst in the right ovary and enlargement of the left uterine tube were observed. Histological examination revealed that the cyst had developed in the hilus of the ovary and was lined by single-layered cuboidal cells. In the left uterine tube, a tumor composed of epithelial cells arranged in tubular structures and pleomorphic cells between the tubular structures was observed. Immunohistochemically, the epithelial cells of the cyst were positive for pan-cytokeratin, cytokeratin 18, CD10, E-cadherin, calretinin and estrogen receptor; the tumor cells of the left uterine tube were positive for pan-cytokeratin, cytokeratin 18, E-cadherin, vimentin, calretinin and estrogen receptor. From these results, the cyst was diagnosed as cystic rete ovarii, and the tumor was diagnosed as adenoma of the uterine tube. This case is the first to demonstrate cystic rete ovarii and uterine tube adenoma in rabbits.

Topics: Adenoma; Animals; Cadherins; Calbindin 2; Fallopian Tubes; Female; Immunohistochemistry; Keratins; Ovarian Cysts; Rabbits; Receptors, Estrogen; Vimentin

Syringomatous adenoma of the nipple (SAN) is a rare benign infiltrative neoplasm that may be confused with low-grade breast carcinomas. We report the case of 71-year-old woman with a fungating left breast mass and subareolar calcifications in the contralateral breast.. Histomorphologic features were evaluated with standard H&E-stained sections. Both lesions were also evaluated by immunohistochemistry for further characterization. A literature review was performed to place the current case in context relative to previous observations.. Both lesions were infiltrating syringomatous adenomas, confirmed by detailed immunohistochemical analyses, which also provided new evidence for the putative sweat duct origin for these tumors. The debated presence of myoepithelial cells in these lesions was newly and convincingly supported in this study by strong diffuse immunostaining of the outer cell layer of the tubules for smooth muscle myosin, cytokeratin 34βE12, cytokeratin 5/6, and p63. Previous reports describing similar detailed immunophenotypical characterization of these uncommon tumors are lacking.. To our knowledge, this case represents only the second reported patient with bilateral SAN and the first such case to be reported in the pathology literature.

Topics: Adenoma; Aged; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mammary Glands, Human; Nipples

This report describes an atypical mammary adenoma with a rare histological feature characterized by proliferating single-layered cystic ducts composed of basaloid cells with frequent myoepithelial differentiation. A 9-year-old, intact female Miniature Pinscher dog had mammary tumors on the thorax. Histologically, one of tumors comprised the proliferation of two types of tubular structures; the single-layered cystic ducts lined by flattened cells and double-layered tubules with luminal cells and outer spindle cells. The former ducts were predominant in the tumor and contained pale basophilic mucus, which was Alcian blue (pH 2.5)-positive, but periodic acid Schiff-negative. Immunohistochemical staining indicated that the cells lining single-layered cystic ducts were negative for the luminal epithelial marker, cytokeratin (CK) CAM5.2, but were constantly positive for basal cell markers CK14 and p63 and frequently positive for SMA. Electron microscopy revealed fine, parallel myofilaments within these single-layered neoplastic cells. These histological and immunohistological examinations suggested that the origin of the tumor was bipotential mammary progenitor cells with predominant differentiation into the myoepithelial progenitor linage.

Topics: Adenoma; Alcian Blue; Animals; Biomarkers; Breast Neoplasms; Cell Differentiation; Cell Proliferation; Cystic Duct; Dog Diseases; Dogs; Epithelial Cells; Female; Immunohistochemistry; Keratins; Microscopy, Electron; Myofibrils

We report a peculiar case of canalicular adenoma of the upper lip in a 57-year-old woman, presenting as two distinct asymptomatic nodules diagnosed and treated surgically within a 2-year period.

Topics: Adenoma; Disease-Free Survival; Female; Humans; Keratins; Lip; Lip Neoplasms; Middle Aged; Neoplasms, Second Primary; Proto-Oncogene Proteins c-kit; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor

Topics: Adenoma; Adnexa Uteri; Adnexal Diseases; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Granulosa Cell Tumor; Humans; Hysterectomy; Keratins; Leiomyomatosis; Microscopy, Electron; Middle Aged; Neoplasms, Multiple Primary; Sertoli-Leydig Cell Tumor; Uterine Neoplasms; Vimentin; WT1 Proteins

Topics: Adenoma; Ear Neoplasms; Ear, Middle; Female; Hearing Loss, Conductive; Humans; Immunohistochemistry; Keratins; Middle Aged; Neuroendocrine Tumors; Otologic Surgical Procedures; Synaptophysin; Tinnitus

Our aim was to examine cell transition events by detecting the frequency of intrapithelial α-smooth muscle actin (SMA)(+)/cytokeratin (CK)(+) cells during colorectal adenoma-carcinoma sequence, in relation to E-cadherin expression. Our further aim was to determine the proliferative activity of intraepithelial α-SMA(+) cells. Histologically healthy, adenoma, and colorectal cancer (CRC) biopsy samples were taken during routine colonoscopy and were included into tissue microarrays (TMAs). Slides immunostained for Ki-67, α-SMA, E-cadherin and pan-cytokeratin were digitalized and analyzed by using a digital microscope software. The proportion of α-SMA(+)/CK(+) cells was significantly higher in CRC samples (3.34 ± 1.01%) compared to healthy (1.94 ± 0.69%) or adenoma (1.62 ± 0.78%) samples (p < 0.01). E-cadherin expression negatively correlated with the number of α-SMA(+) cells. The majority of intraepithelial α-SMA(+) cells were in the proliferative phase. During tumor progression, the appearance of dot-like α-SMA staining in CK positive cells may indicate the initial phase of the epithelial-to-mesenchymal transition (EMT). The high proportion of intraepithelial α-SMA(+) proliferating cells may refer to their increased plasticity compared to differentiated cells. The negative correlation between E-cadherin and intraepithelial α-SMA expression suggests that EMT is facilitated by a loss of epithelial cell contact.

Topics: Actins; Adenoma; Biomarkers, Tumor; Cadherins; Cell Differentiation; Cell Transformation, Neoplastic; Colon; Colorectal Neoplasms; Disease Progression; Epithelial-Mesenchymal Transition; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Longitudinal Studies; Neoplasm Staging; Prognosis; Rectum; Tissue Array Analysis

Feline mammary carcinomas are highly aggressive neoplasms. Several mechanisms are thought to be involved in their progression, including the loss of epithelial adhesion molecules. The present study was carried out on 21 adenomas and 139 mammary carcinomas. Of the carcinomas, 66 were not reported to have metastasized, while the remaining 73 had evidence of regional lymph node metastasis at the moment of diagnosis. The relationship was examined between the expression of the E-cadherin-β-catenin complex and basal (CK5/6, CK14) and luminal (CK8/18) cytokeratin expression. In the medical literature, carcinomas expressing basal cytokeratins are reported as having a poor prognosis in human breast cancer. Results revealed that preservation of the expression of E-cadherin and β-catenin is a significant feature of carcinomas without metastasis, whereas carcinomas with metastasis reveal the loss of one or both adhesion molecules. Additionally, basal cytokeratin expression was statistically associated with the presence of regional metastasis. Furthermore, the expression of E-cadherin-β-catenin was significantly correlated with the high expression of CK18 and low expression of CK5/6.

Topics: Adenoma; Animals; beta Catenin; Biomarkers, Tumor; Cadherins; Carcinoma; Cat Diseases; Cats; Female; Immunohistochemistry; Keratins; Lymphatic Metastasis; Mammary Neoplasms, Animal; Neoplasm Grading; Vimentin

Canalicular adenoma is an uncommon benign tumour that generally arises in the minor salivary glands of individuals over 60 years old. This study illustrates a case of canalicular adenoma in a 70-year-old female, presenting as two distinct asymptomatic nodules in the upper lip. Immunohistochemistry analysis was performed. Clinical features, management, histology and immunoprofile from this case and from the literature are discussed.

Topics: Adenoma; Aged; Asymptomatic Diseases; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Ki-67 Antigen; Lip Neoplasms; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Transcription Factors; Tumor Suppressor Proteins

Topics: Abscess; Adenoma; Adenoma, Sweat Gland; Biomarkers; Breast Diseases; Breast Neoplasms; Female; Fistula; Humans; Keratin-7; Keratins; Mucin-1; Nipples; Paget's Disease, Mammary; Receptor, ErbB-2; Sweat Gland Neoplasms

The searching of the reliable and repeatable immunohistochemical markers in the differential diagnosis of the thyroid's differentiated follicular epithelial neoplasms has been continuing. Recently, the studies have majored on immunohistochemical markers such as high-molecular weight cytokeratin (HMW-CK), galectin-3, cytokeratin 19, and p27. We aimed to evaluate the differences of the expressions of the proliferating cell nuclear antigen (PCNA), thyroid transcription factor-1 (TTF-1), Ki-67, p63, p53, and HMW-CK among the papillary thyroid carcinomas (PTCs), follicular carcinomas (FCs), and follicular adenomas (FAs). Thirty-nine patients with the diagnoses of the PTC, FC, and FA in the archives of the Izmir Tepecik Training and Research Hospital Pathology Laboratory registries in between 2004 and 2009 were included in the study. Immunohistochemical stains for PCNA, TTF-1, Ki-67, p63, p53, and HMW-CK were applied. The results were analyzed statistically by using Statistical Package for the Social Sciences (SPSS) for Windows 16.0 program (SPSS Inc., IBM, Somers, New York, USA). In all 3 groups, all tumors showed PCNA and TTF-1 positivity. Ki-67 proliferation index varied in a wide range in all groups. Although it was not statistically significant, 19 of 39 tumors (7 PTCs, 2 FCs, and 10 FAs) were stained with p63. The results of the immunoreactivity seen in PTCs with p53 (41.2%) and HMW-CK (52.9%) were statistically significant. The tumors in the other 2 groups (FC and FA) showed no reactivity with HMW-CK. Although the differential diagnosis of the thyroid follicular neoplasms are based on the histologic and cytomorphological criteria, p53 and HMW-CK positivity might be undertaken in favor of the diagnosis of the PTC.

Topics: Adenoma; Adolescent; Adult; Age Distribution; Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Papillary; Child; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Membrane Proteins; Middle Aged; Molecular Weight; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Sex Distribution; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule; Thyroid Nuclear Factor 1; Transcription Factors; Tumor Suppressor Protein p53; Young Adult

Topics: Actins; Adenoma; Adult; Biomarkers, Tumor; Biopsy; Breast Neoplasms; Carcinoembryonic Antigen; Cell Nucleus; Female; Glial Fibrillary Acidic Protein; Hemorrhage; Humans; Keratins; Neoplasms, Multiple Primary; Nipples; Skin Ulcer

To study the clinicopathologic features, immunophenotypes and differential diagnosis of thyroid carcinoma showing thymus-like differentiation (CASTLE).. The clinical and pathologic features of 8 cases of CASTLE were reviewed. Immunohistochemical study was performed using a panel of antibodies. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also carried out.. There were altogether 4 males and 4 females. The age of the patients ranged from 25 to 57 years (mean = 48.8 years). All of them presented with painless mass at the anterior neck. Two patients also complained of hoarseness of voice. On CT scan, the tumor had a low density with contrast enhancement. Seven cases were located in the mid to lower pole and the remaining one in the upper pole of thyroid gland. Four cases were relatively circumscribed. The other 4 cases showed evidence of extrathyroidal invasion. Grossly, the tumor had a nodular or lobulated appearance and was gray-white in color, with a mean diameter of 4.3 cm. Microscopically, the tumor was infiltrative and consisted of islands, nests or lobules of epithelial cells separated by thick fibrous septa. The fibrous stroma showed various degree of lymphoplasmacytic infiltration, resulting in a prominent lymphoepithelioma-like pattern in 3 cases. Two cases showed squamoid differentiation, mimicking thymic Hassall corpuscles. Immunohistochemically, the tumor was consistently positive for cytokeratins, CD5, bcl-2, p63 and CD117. CEA was variably expressed. The staining for thyroglobin and TTF1 was negative. There was no labeling for EBER in all the cases. Two patients experienced local recurrence at 22 months and 12 years after surgery, respectively. They were treated with re-resection. All patients remained well on follow up. The duration of follow up ranged from 4 to 55 months.. CASTLE is a low-grade thyroid carcinoma with the morphologic features and immunophenotypes overlapping with those of thymic carcinoma. Awareness of this rare entity is important to both the pathologists and clinicians.

Topics: Adenoma; Adult; Carcinoma; CD5 Antigens; Cell Differentiation; Disease-Free Survival; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-bcl-2; Reoperation; Thymus Gland; Thymus Neoplasms; Thyroid Neoplasms; Tomography, X-Ray Computed

Pleomorphic adenoma is the most common neoplasm of the salivary glands and is most commonly located in the parotis followed by the submandibular glands. Its localization in the minor salivary glands is mostly reported in the palate. Few publications report pleomorphic adenoma cases located in the lip. We present a 35-year-old male patient with a pleomorphic adenoma located in the upper lip.

Topics: Actins; Adenoma; Adenoma, Pleomorphic; Adult; Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Lip Neoplasms; Male; Myoepithelioma; Salivary Gland Neoplasms; Salivary Glands, Minor

Topics: Adenoma; Humans; Keratins; Male; Middle Aged; Nails; Skin Neoplasms

Ectopic breast tissue is defined as glands located outside of the breast. Ectopic breast tissue should be excised because it may develop benign or malignant pathologic processes. Although lactation changes can occur, lactating adenoma in the vulva are extremely rare.. We report a case of a young woman who presented with multiple vulvar masses during her pregnancies. The masses were excised, and histology confirmed multiple vulvar lactating adenomas.. Vulvar lactating adenoma may be misdiagnosed as adenocarcinoma in frozen diagnosis and aspiration cytology if breast tissue is not anticipated. Although the incidence of ectopic mammary tissue of the vulva is low, this possibility should be considered when evaluating patients with mass lesions of the vulva in the appropriate clinical setting.

Topics: Actins; Adenoma; Adult; Breast; Choristoma; Female; Humans; Keratins; Lactation; Membrane Proteins; Pregnancy; Pregnancy Complications, Neoplastic; Receptor, ErbB-2; Vulvar Neoplasms

Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. Our material consisted of 36 GH-secreting pituitary adenomas (21 female,15 male, mean age 42.5±10.5), operated at our center between 2003 and 2010. Immunostaining for MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. Staining for MGMT was <10% (score 1) in 30 (83.3%), 10-25% (score 2) in 3 (8.3%), 25-50% (score 3) in 2 (5.6%) and >50% (score 4) in 1 (2.8%) of the tumors, respectively. There was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents, Alkylating; Cell Nucleus; Dacarbazine; DNA Modification Methylases; DNA Repair Enzymes; Drug Resistance, Neoplasm; Female; Human Growth Hormone; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Proteins; Pituitary Neoplasms; Protein Transport; Temozolomide; Tumor Suppressor Proteins

Topics: Adenocarcinoma, Follicular; Adenoma; Aged; Carcinoma, Renal Cell; Chromogranin A; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Keratins; Kidney Neoplasms; Neprilysin; Thyroglobulin; Thyroid Neoplasms; Transcription Factors; Vimentin

Twenty cases of adenomatoid spindle cell thymomas are presented. The patients are 13 males and 7 females between 7 and 82 years of age (mean: 55 y). Clinically, all patients presented with symptoms of chest pain and shortness of breath. Radiologically, an anterior mediastinal mass was discovered, and complete surgical resection was performed in all of the patients. Grossly, the tumors were described as well-defined solid tumor masses surrounded by membranous tissue, which at cut surface show a light tan homogenous surface. Areas of necrosis, hemorrhage, and/or cystic degeneration were not observed in any of the cases. Histologically, all tumors showed similar histological features and were characterized by the presence of a spindle cellular proliferation with an "adenomatoid-like" appearance, which at higher magnification showed the presence of cells with a signet-ring cell-like appearance. Rare mitotic figures were seen in some cases. Seven tumors showed transcapsular invasion, whereas 13 cases were encapsulate. Immunohistochemical studies showed positive staining for broad-spectrum keratin and keratin 7 with only scattered cells positive for calretinin and epithelial membrane antigen. Other markers including S-100 protein, desmin, smooth muscle actin, and α-feto protein were negative. Follow-up information ranging from 4 to 96 months (average: 32.3 mo) was obtained in 17 patients showing that all patients were alive. The cases herein described highlight the importance of recognizing this unusual pattern of spindle cell thymomas to avoid misdiagnosis with other tumors, namely, when dealing with small mediastinoscopic biopsies.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Female; Humans; Keratins; Male; Middle Aged; Thymoma; Thymus Neoplasms; Young Adult

We present a series of a distinct tumorous entity named renal angiomyoadenomatous tumor (RAT). Five cases were retrieved from the consultation files of the authors. Histologic and immunohistochemical features were evaluated. Sequencing analysis of coding region of the VHL gene was carried out in all cases. The tumors were composed of admixture of an epithelial clear cell component and prominent leiomyomatous stroma. Epithelial cells formed adenomatous tubular formations endowed with blister-like apical snouts. All tubular/glandular structures were lined by a fine capillary network. The epithelial component was positive for epithelial membrane antigen, CK7, CK20, AE1-AE3, CAM5.2, and vimentin in all cases. In all analyzed samples, no mutation of the VHL gene was found. RAT is a distinct morphologic entity, being different morphologically, immunohistochemically, and genetically from all renal tumors including conventional clear cell carcinoma and mixed epithelial and stromal tumor of kidney.

Topics: Adenoma; Aged; Aged, 80 and over; Biomarkers; Epithelial Cells; Female; Humans; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Loss of Heterozygosity; Male; Middle Aged; Mucin-1; Mutation; Vimentin; Von Hippel-Lindau Tumor Suppressor Protein

Transforming growth factor-beta1 (TGF-beta1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-beta1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-b levels, showing a stepwise increase in the mucosa-adenoma-carcinoma sequence, active TGF-beta1 levels are increased only in carcinomas but not in premalignant adenomas. Furthermore, solely active TGF-beta1 levels are associated with the stage of the carcinomas and worse patient prognosis. Active TGF-beta1 levels correlated significantly with plasminogen activator inhibitor (PAI)-1, alpha-smooth muscle actin (SMA) and several matrix-remodeling proteinases. Interestingly, SMA levels are also significantly increased in colorectal carcinomas but not in adenomas, suggesting that despite the enhanced total TGF-beta1 levels, myofibroblast accumulation is not (yet) occurring in these premalignant neoplasias. The correlation between active TGF-beta1 and SMA expression in tumors indicates that tumor-promoting myofibroblasts might arise as a result of increased TGF-beta1 activation. These data underline the significance of the interaction between malignant cells and (myo)-fibroblasts in the tumor microenvironment, modulating the biologic behavior of colorectal cancer.

Topics: Actins; Adenoma; Biomarkers, Tumor; Carcinoma; Colorectal Neoplasms; Desmin; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; HT29 Cells; Humans; Immunohistochemistry; Keratins; Male; Muscle, Smooth; Plasminogen Activator Inhibitor 1; Reproducibility of Results; Sensitivity and Specificity; Smad2 Protein; Transforming Growth Factor beta1; Urokinase-Type Plasminogen Activator; Vimentin

Intercalated duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of intercalated duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all ducts (100%). Normal intercalated ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal intercalated ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Female; Humans; Hyperplasia; Keratins; Male; Microfilament Proteins; Middle Aged; Muramidase; Neoplasms, Multiple Primary; Parotid Gland; Receptors, Steroid; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Submandibular Gland; Young Adult

The report presents a very rare case of papillary adenoma of the lung in a 61-year old man, described for the first time in the Polish literature.

Topics: Adenoma; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Pulmonary Surfactant-Associated Protein A; Respiratory Mucosa

A 41-year-old man presented with headache, right-sided ophthalmic pain and visual deficit. His neurological examination was normal except for bitemporal hemianopsia and right lower quadranopsia. MRI demonstrated a mass arising from the pituitary gland. Hormonal analysis revealed an elevated prolactin level of 4700 ng/mL (normal 4.04-15.2 ng/mL). MRI revealed hypointense signal on T2-weighted images. Moreover, we also concluded that foci with no intravenous contrast enhancement represent the amyloid deposits. The patient underwent trans-sphenoidal resection of the pituitary adenoma. Histological examination revealed an adenoma with spheroid amyloid deposits adjacent to prolactin-staining adenoma cells. The patient recovered from the surgery without complications.

Topics: Adenoma; Adult; Amyloid; Birefringence; Congo Red; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Pituitary Hormones, Anterior; Pituitary Neoplasms; Prolactin

To study Twist expression in thyroid papillary carcinoma (PTC) by immunohistochemistry and to assess its usefulness as marker in the differential diagnosis of PTC, follicular adenomas (FA) and benign papillary lesions (BPL).. Fifty cases of PTC, 48 cases of FA and 47 cases of BPL were evaluated using manual tissue chip and SP immunohistochemical stain to detect the expression of Twist and HBME-1, and comparing the staining to that of cytokeratin 19 (CK19).. In PTC, positive rates of Twist, HBME-1 and CK19 were 100% (48/48), 94.0% (47/50) and 78.0% (39/ 50) respectively; in FA, positive rates were 0, 6.7% (3/45) and 0 respectively; in BPL, positive rates were 7.0% (3/34), 2.1% (1/47) and 0, respectively. The differences between PTC and FA and between PTC and BPL were both statistically significant (P = 0. 000). The sensitivity of Twist, HBME-1 and CK19 was 100%, 94.0% and 78.0%; the specifity was 96.4%, 95.7% and 100%; overall accurary was 97.7%, 95.1% and 91.9%, respectively.. Positive rates of Twist is higher than the other markers in PTC. Immunohistochemical staining of Twist has important significance in the differential diagnosis of thyroid lesions. Twist immunohistochemistry maybe helpful in diagnosis and differential diagnosis of PTC.

Topics: Adenocarcinoma, Follicular; Adenocarcinoma, Papillary; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Galectin 3; Immunohistochemistry; Keratin-19; Keratins; Nuclear Proteins; Thyroid Neoplasms; Thyroid Nodule; Twist-Related Protein 1

Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Aged; Aging; beta Catenin; Cadherins; Cell Count; Cytoplasm; Female; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pituitary Neoplasms; Thyrotropin; Tissue Fixation

Hyalinizing trabecular tumor (HTT) is a rare thyroid tumor of follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. This tumor is known to share morphological and architectural similarities with paraganglioma and medullary thyroid carcinoma, as well as the nuclear features and RET/PTC1 translocations of papillary thyroid carcinoma. These tumors are not associated with RAS or BRAF mutations. Whether the presence of RET alterations in HTT are sufficient molecular proof of its relationship with papillary thyroid carcinoma (PTC) is still to be defined. Of great interest is the characteristic strong peripheral cytoplasmic and membranous staining of the tumor cells with MIB1 immunostain, not seen in any other thyroid neoplasm. Although cases of malignant HTT have been recorded, HTT should be considered a benign neoplasm or, at most, a neoplasm of extremely low malignant potential.

Topics: Adenoma; Adult; Aged; Biomarkers, Tumor; Calcitonin; Cell Nucleus; Chromogranin A; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Paraganglioma; Sex Characteristics; Thyroid Neoplasms

Topics: Actins; Adenoma; Adult; Cell Differentiation; Eccrine Glands; Female; Humans; Immunohistochemistry; Keratins; Muscle, Smooth

Little is known about the behavior of the ovarian surface epithelium (OSE), which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK) staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year) mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and platelet-derived growth factor receptors alpha and beta in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

Topics: Adenoma; Animals; Cell Differentiation; Cell Proliferation; Cyclooxygenase 1; Cyclooxygenase 2; Cystadenoma, Serous; Epithelial Cells; Female; Fluorescent Antibody Technique; GATA4 Transcription Factor; Humans; Immunoenzyme Techniques; Inflammation; Keratins; Mice; Ovarian Neoplasms; Ovary; Proliferating Cell Nuclear Antigen; Receptors, FSH; Receptors, Platelet-Derived Growth Factor

We are reporting a case of a patient with primary hyperparathyroidism because of an unusual parathyroid adenoma. The tumor had an extensive myxofibrous stroma without an identifiable lipomatous component. Though moderate to extensive myxoid alteration of the stroma has been reported in lipoadenomas, to the best of our knowledge, this is the first parathyroid adenoma in which the myxomatous component was recognized grossly and which lacked a stromal adipose component.

Topics: Adenoma; Alkaline Phosphatase; Biomarkers, Tumor; Calcium; Humans; Hyperparathyroidism; Keratins; Male; Middle Aged; Mucins; Parathyroid Hormone; Parathyroid Neoplasms; Phosphorus; Thyroidectomy

Nephrogenic adenoma is a rare lesion of the urinary tract. The diagnosis usually is straightforward when characteristic microscopic and clinical findings are present, and the entity is familiar. However, misdiagnosis, in particular of adenocarcinoma of the prostate gland, may occur. Immunohistochemical stains often are needed to make such a distinction, but currently available markers offered only partial help. It recently was demonstrated that nephrogenic adenoma in renal transplant patients originated from the renal tubular epithelium. This newly proved, but long sought information may be helpful in the differential diagnosis of nephrogenic adenoma. In this study, we investigated the expression of a renal transcription factor, PAX2, in 39 nonrenal transplant-related nephrogenic adenomas, 100 adenocarcinomas of the prostate gland, and 47 urothelial carcinomas of the urinary tract. A strong and distinct nuclear staining of PAX2 was found in all 39 cases of nephrogenic adenoma (100%), but not in normal prostate tissue, normal urothelium, adenocarcinomas of the prostate gland, and invasive urothelial carcinomas. Focal CD10 was detected in six of 13 nephrogenic adenomas in the superficial papillary component and in normal prostate epithelium, normal urothelium, lymphocytes, adenocarcinoma of the prostate gland, and urothelial carcinoma. There was no uroplakins detected in nephrogenic adenoma. Therefore, these findings are suggesting that nephrogenic adenoma in nonrenal transplant patients may also arise from the renal epithelium, as did the comparable lesions after transplantation. PAX2 is a specific and sensitive immunohistochemical marker in identification and differential diagnosis of nephrogenic adenoma.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Neprilysin; PAX2 Transcription Factor; Sensitivity and Specificity; Urologic Neoplasms

Metanephric adenoma (MA), a well-described renal neoplasm, usually behaves in a benign fashion. It may have areas that are morphologically similar to papillary renal cell carcinoma (RCC) type, or epithelial (tubular predominant) type Wilms' tumor. Prior immunohistochemical studies of MA have reported variable staining patterns. Alpha-methylacyl-CoA racemase (AMACR), a molecular marker for prostate carcinoma, has subsequently been found to be overexpressed in breast, colorectal and ovarian cancers, among others. Recent microarray analysis of renal tumors has shown an increase of AMACR mRNA levels in papillary RCC but not in other subtypes. We investigated the utility of immunohistochemical staining for AMACR, cytokeratin 7(CK7), CD57 and WT1 to differentiate between the above-mentioned three neoplasms. Immunohistochemical stains were performed on paraffin-embedded tissue sections from 25 papillary RCC, 10 MAs and eight Wilms' tumors. AMACR was positive in one (10%) of 10 MAs and 24 (96%) of 25 papillary RCC, while it was negative in all Wilms' tumors. CK7 was positive in 20 of 25 papillary RCCs, focally positive in one Wilms' tumor and was negative in all MAs. CD57 was positive in all six MAs that were stained, focally positive in one of 25 papillary RCC and one of eight Wilms' tumors. WT1 was positive in seven of 10 MAs, three of 25 papillary RCCs and all eight Wilms' tumors. In conclusion, diffuse and strong immunoreactivity for AMACR may be useful in differentiating papillary RCC from MA but a panel which includes AMACR, CK7 and CD57 is better in this differential diagnosis. AMACR is not helpful in differentiating MA from Wilms' tumor, but CD57 is helpful in this differential diagnosis. WT1 may be useful in separating Wilms' tumor from MA and papillary RCC but is not helpful in differentiating MA from papillary RCC.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; CD57 Antigens; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Racemases and Epimerases; Wilms Tumor; WT1 Proteins

The aim of this study was to investigate the immunohistochemical expression of p16, p53, and p63 proteins according to some pathologic parameters related to colorectal adenomas and adenocarcinomas such as grade of dysplasia and histologic type.. Immunohistochemistry with the antibodies p16, p53, and p63 was performed in tubular, tubular-villous, and villous adenomas (n = 30) and in well, moderately, and poorly differentiated adenocarcinomas (n = 30). The p63-positive cases were submitted to double immunolabeling with the cytokeratin 5 (CK5).. The p16 and p53 labelings were observed in some adenomas and adenocarcinomas but without any association with p63 expression, histologic type, or grade of differentiation of the neoplasm. P63 expression was found mainly in the villous adenomas and in the poorly differentiated adenocarcinomas. The poorly differentiated adenocarcinomas also exhibited coexpression of CK5 and p63.. Despite both p16 and p53 having been detected in colorectal neoplasms, they were not related to the different histologic variables nor to the expression of p63. However, p63 expression was closely associated with villous adenomas and poorly differentiated adenocarcinomas. Thus, p63 may represent a marker of poor differentiation in colorectal neoplasms. The coexpression of p63 and CK5 observed in this study could be related to divergent differentiation during the development of colorectal cancer, although further studies are warranted to refine the understanding of this process.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Colorectal Neoplasms; DNA-Binding Proteins; Genes, p16; Genes, p53; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Phosphoproteins; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Colitis, Ulcerative; Colorectal Neoplasms; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Keratin-20; Keratin-7; Keratins; Mucins; Precancerous Conditions

Topics: Adenoma; Adult; Female; Gene Expression Regulation, Neoplastic; Humans; Intracellular Membranes; Keratins; Pancreatic Neoplasms; Ribosomes

The histogenetic origin of salivary gland tumours is not clear. In normal tissues smooth muscle actin (SMA) is expressed in myoepithelial cells, CK14 immunoreactivity is seen in myoepithelial and basal cells and CK10 in keratinized squamous epithelium. In this study, we examine the immunophenotypic properties of salivary gland tumours in order to obtain further insight into their histogenesis. 30 cases of salivary gland tumours (18 pleomorphic adenomas, 8 Warthin's tumours, 2 basal cell adenomas, 2 acinic cell carcinomas) were included in our study. Cytokeratin (CK) 10, CKI4, CKI7, CK18, CK 19, and smooth muscle actin (SMA) immunostains were applied to the sections. Immunoreactivities were detected and the statistical significance was evaluated by chi square test. SMA was not detected in Warthin's tumour (p < 0.0001). CK14 was found in all tumours except acinic cell carcinomas (p < 0.0001). CK10 immunoreactivity was observed in 5 Warthin's tumour. In conclusion, pleomorphic adenomas and basal cells adenomas originate from stem cells. Immunophenotypic profile of Warthin's tumour is suggestive of an embryological remnant origin.

Topics: Actins; Adenolymphoma; Adenoma; Adenoma, Pleomorphic; Carcinoma, Acinar Cell; Humans; Immunophenotyping; Keratins; Neoplasm Proteins; Organ Specificity; Protein Isoforms; Retrospective Studies; Salivary Gland Neoplasms

The aim of the study was to evaluate the expression of galectin-3 (gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) in thyroid gland tumors with follicular growth pattern with particular focus on their use in differential diagnosis. A series of 139 cases - 87 follicular adenomas (FAs), 26 follicular carcinomas (FCs), and 26 cases of the follicular variant of papillary carcinoma (FVPC) was studied. Expression of gal3 was found in 29/87 (33%) of FAs, in 13/26 (50%) of FCs, and in 24/26 (92%) of FVPCs. Expression of CK19 was found in 11/87 (13%) of FAs, in 4/26 (15%) of FCs, and in 17/26 (65%) of FVPCs. Expression of NCAM was found in 60/87 (69%) of FAs, in 20/26 (77%) of FCs, and in 7/26 (27%) FVPCs. Expression of Ecad was found in 81/87 (93%) of FAs, in 22/26 (85%) of FCs, and in 17/26 (65%) of FVPCs. The sensitivity and specificity of gal3 for malignancy were 0.70 and 0.85, of CK19 0.48 and 0.98, of NCAM 0.28 and 0.47, and of Ecad 0.48 and 0.20, respectively. A significant difference (p < 0.05) in expression of all studied markers between FVPC versus FA and FC was found, in contrast to FA and FC. Therefore, the use of gal3 and CK19 in differential diagnosis of FVPC versus FA and FC can be recommended.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cadherins; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Female; Galectin 3; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neural Cell Adhesion Molecule L1; Thyroid Neoplasms

It has generally been accepted that pseudomyxoma peritonei/disseminated peritoneal adenomucinosis originates from appendiceal low-grade adenomatous mucinous tumors. A woman who underwent an appendectomy 42 years ago, presented with a unilateral ovarian tumor whose immunohistochemical phenotype and its association with a teratoma, strongly suggest that pseudomyxoma peritonei originated from a ruptured mucinous tumour arising from a mature cystic teratoma.

Topics: Adenoma; Aged; Appendectomy; Douglas' Pouch; Fallopian Tubes; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-20; Keratins; Omentum; Ovarian Neoplasms; Ovariectomy; Pseudomyxoma Peritonei; Rupture, Spontaneous; Splenectomy; Teratoma

Since its description, hyalinizing trabecular adenoma (HTA) of the thyroid has been a controversial entity. Some have considered it a unique entity, some have considered it a variant of papillary carcinoma (PC), and still others have considered it a nonspecific pattern that may be seen with a variety of thyroid lesions. Complicating the matter, studies demonstrating metastases have shown entities that do not appear to be HTAs as originally described, and molecular studies showing changes of PC have used methods that are not specific. This study reviews our experience with thyroid lesions that showed at least some histologic features of HTA and presents the immunohistochemical findings for these lesions using antibodies employed for the diagnosis of PC.. Our files were reviewed for all thyroid resection reports describing lesions with hyalinized or sclerotic stroma and a trabecular architecture within the diagnosis or diagnostic comment. All cases were reviewed and classified as either HTA or as different lesions based upon histologic features. Immunohistochemistry with antibodies to HBME1, CK19 and p63 was performed with all lesions and with a series of controls.. Eighteen thyroid lesions with prominent sclerosis or hyalinization and trabecular architecture were identified. Only 4 of these were found to completely match the histologic and cytologic descriptions of HTA by HE review. The other cases showed histologic features more compatible with other diagnoses including cellular adenomatoid nodule (5), follicular adenoma (4), follicular variant of PC (FVPC) (3), and epithelial neoplasm with features of FVPC (2). All HTAs lacked immunoreactivity for HBME1, CK19 and p63. All cases deemed to be adenomatoid nodules, follicular adenomas and epithelial neoplasms showed no immunoreactivity for HBME1 and CK19 and, of these, only a single AN showed immunoreactivity for p63. Cases deemed to be FVPCs showed diffuse immunoreactivity for HBME1 and CK19 and 1 reacted with antibodies to p63. Of control PCs and other thyroid lesions, reactivity for HBME1, CK19, and p63 was observed in 8/8, 7/7, and 7/8 and 3/27, 7/27, and 7/27 cases, respectively.. A sclerotic or hyalinized stroma with a trabecular growth pattern may be seen in a number of different thyroid lesions and, when seen, is usually a focal feature of a lesion other than HTA. Immunohistochemistry may be of assistance as cases of FVPC with prominent hyalinization and trabeculation will show immunoreactivity for HBME1 and CK19, whereas HTAs and other thyroid lesions with hyalinization and trabeculation will not.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Humans; Hyalin; Immunohistochemistry; Keratins; Sclerosis; Thyroid Neoplasms

Oncocytic lipoadenomas of salivary gland are extremely rare tumors with only two previously reported cases. In this paper, we describe an additional example of oncocytic lipoadenoma showing sebaceous differentiation, a hitherto unreported occurrence. The tumor was encapsulated and measured 3 x 2.5 x 2 cm. Microscopically, the tumor comprised a mixture of oncocytes with "light" and "dark" cells intimately associated with mature adipose tissue. The oncocytes were positive for low molecular keratin, epithelial membrane antigen (EMA), and keratin 7, with only a small subgroup of cells expressing high-molecular-weight keratin, keratin 5/6, keratin 19, and p63. Terminally differentiated sebaceous cells were positive for EMA and keratin 14 only. Calponin and actins were negative, indicating a lack of myoepithelial cells in the tumor. The keratin profile and p63 expression of this oncocytic lipoadenoma suggest the presence of a dual cell population somewhat similar to the dual cell population described in some ultrastructural studies of pure salivary gland oncocytomas and may represent partial basal-cell differentiation. The presence and nature of a dual cell population in oncocytic neoplasms of salivary glands merit further investigation to confirm these observations.

Topics: Adenoma; Female; Humans; Immunohistochemistry; Keratins; Lipoma; Middle Aged; Parotid Neoplasms

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. We evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid (LGALS3, FN1, CITED1 and KRT19), and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas (67 papillary, six follicular, eight Hürthle cell and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products, for example, galectin-3 (GAL3), fibronectin-1 (FN1), CITED1, cytokeratin-19 (CK19) and HBME1. Non-neoplastic thyroids (29 adenomatous and 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy, and highly specific (> or = 90%) for carcinoma compared to adenoma. GAL3, FN1 and/or HBME1 expression was seen in 100% of carcinomas (85/85) and in 24% of adenomas (5/21). Coexpression of multiple proteins was seen in 95% of carcinomas and only 5% of adenomas (P<0.0001). Coexpression of FN1 and GAL3 (FN1+ GAL3+, 70/85) or FN1 and HBME1 (FN1+ HBME1+, 53/85) was restricted to carcinomas, while their concurrent absence (FN1- GAL3- or FN1- HBME1-, 18/21 adenoma) was highly specific (96%) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n=16), CK19 (n=9) and CITED1 (n=7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.

Topics: Adenoma; Apoptosis Regulatory Proteins; Biomarkers, Tumor; Diagnosis, Differential; Fibronectins; Galectin 3; Humans; Immunohistochemistry; Keratins; Nuclear Proteins; Statistics as Topic; Thyroid Gland; Thyroid Neoplasms; Trans-Activators; Transcription Factors

Adenomatoid tumors are relatively uncommon benign neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Rare extragenital adenomatoid tumors have been identified in the adrenal glands, heart, mesentery, pleura, and lymph nodes. In the adrenal gland, adenomatoid tumors may pose a diagnostic challenge. The differential diagnosis includes adrenocortical carcinoma and metastatic carcinoma, especially signet ring cell carcinoma. Because of its glandular pattern, an adenomatoid tumor may be confused with an adenocarcinoma. We present 3 cases of adrenal adenomatoid tumors, including one with a concurrent large hemorrhagic vascular adrenal cyst. The adenomatoid tumors were unilateral, appeared solid and white, and varied from 1.7 to 4.2 cm in diameter. They occurred in 3 male patients aged 33, 33, and 46 years. One patient presented with abdominal pain due to the presence of a concurrent large adrenal cyst. The tumor was an incidental radiological finding in another case and was discovered during the course of a workup for hypertension in the third case. The light microscopic appearances were consistent with those of typical adenomatoid tumors. Immunohistochemical stains for calretinin and cytokeratin 5/6 were positive, confirming the tumors' mesothelial origin. Ultrastructural studies performed in 2 cases revealed microvilli and desmosomes. Follow-up showed no evidence of recurrence or metastasis. In our experience, the key to the diagnosis of this rare benign tumor is to consider adenomatoid tumor in the differential diagnosis of any glandular tumor occurring in the adrenal gland.

Topics: Adenocarcinoma; Adenoma; Adrenal Gland Neoplasms; Adult; Biomarkers, Tumor; Calbindin 2; Carcinoma, Signet Ring Cell; Cysts; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Calcium Binding Protein G; Treatment Outcome

The entity of serrated adenoma of the colorectum was first proposed in 1990, and it was characterized as epithelial neoplasia combining the architectural features of a hyperplastic polyp with the cytological features of an adenoma. Over the past few years, various clinicopathological studies on serrated adenoma have been reported, but its histogenesis remains unclear. Recently the existence of a "serrated neoplasia pathway" leading to malignancy, which is different from the so-called adenoma-carcinoma sequence, has been discussed. Yao et al. reported that hyperplastic polyps and serrated adenomas share a common cell lineage with gastric differentiation. To clarify the existence of the serrated neoplasia pathway, we performed immunohistochemical staining of cytokeratin 7 (CK7) and cytokeratin 20 (CK20), which are commonly used to determine the primary site of a metastatic lesion, and we examined the pattern of CK7/CK20 expression in various colorectal lesions including 44 serrated adenomas, 25 hyperplastic polyps, 20 traditional adenomas, and 48 carcinomas. An obvious difference existed in the pattern of CK7/CK20 expression between the serrated lesions (hyperplastic polyps and serrated adenomas) and others. The majority of serrated adenomas and hyperplastic polyps presented a CK7+/CK20+ pattern, whereas most conventional adenomas and adenocarcinomas expressed CK7-/CK20+. Adenocarcinoma developing in serrated adenoma also presented a CK7+/CK20+ pattern. There are several reports that CK7 is a possible marker of transient dedifferentiation in the gastric carcinogenesis process. Taken together with the present results, a distinct pathway of colorectal carcinogenesis must exist, which is different from the adenoma-carcinoma sequence. CK7 is a possible marker for the serrated neoplasia pathway of colorectal carcinogenesis.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Transformation, Neoplastic; Colonic Polyps; Colorectal Neoplasms; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged

Topics: Adenoma; Cell Differentiation; Female; Hair Diseases; Humans; Keratins; Middle Aged; Skin Neoplasms

Topics: Adenoma; Carcinoma, Neuroendocrine; Cell Nucleus; Chromogranins; Cytoplasm; Ear Neoplasms; Ear, Middle; Humans; Immunohistochemistry; Keratin-7; Keratins; Pancreatic Polypeptide

The pattern of immunohistochemical expression of cytokeratins 7 (CK 7) and 20 (CK 20) is commonly used to assess possible primary sites of metastatic carcinomas. Because pituitary tumors are almost always benign, there has been little interest in their cytokeratin profile. However, we recently reported the use of CK 7/20 expression to document malignant progression and metastasis of a pituitary tumor, indicating the potential diagnostic usefulness of the CK 7/20 profile of pituitary adenomas. We analyzed CK 7/20 expression in 97 pituitary adenomas subclassified by immunohistochemical hormone expression. In about 90% of all subtypes, CK 7 was either negative or reactive in only a few scattered cells. Corticotrophs and sparsely granulated growth hormone-positive adenomas were consistently CK 20 positive (and CK 7 negative) whereas all other subtypes were almost always CK 20 negative. This CK 20-positive, CK 7-negative profile is previously described consistently only in colonic adenocarcinomas. This study documents that subtypes of pituitary adenomas have different CK 7/20 profiles. Whereas this pattern is likely to have diagnostic usefulness in only rare adenomas, the presence of a unique CK signature in corticotrophs and sparsely granulated growth hormone-positive adenomas, subtypes particularly noted for invasive and aggressive behavior, merits further investigation.

Topics: Adenoma; Biomarkers; Biomarkers, Tumor; Cell Count; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Pituitary Neoplasms; Retrospective Studies

To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in-situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase-cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard.. Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 +/- 0.04% in normal mucosa, 0.42 +/- 0.04% in adenomas and 1.97 +/- 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 +/- 0.03%, 0.62 +/- 0.06% and 1.78 +/- 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P < 0.01).. Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma-carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Apoptosis; Cell Count; Colon; Colorectal Neoplasms; Female; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Intestinal Mucosa; Keratins; Male; Middle Aged

The canalicular adenoma is an uncommon, benign salivary gland tumour that most frequently occurs in the upper lip. Although the incidence of multifocal epithelial tumours of the minor salivary is very low, canalicular adenoma sometimes present as a multifocal lesion. We present a case of multifocal canalicular adenomas of upper lip in a woman aged 68 years and discuss their features, emphasising diagnosis, clinical behaviour, treatment, histological and immunohistochemical aspects.

Topics: Adenoma; Aged; Biopsy, Fine-Needle; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Lip; Salivary Gland Neoplasms; Salivary Glands, Minor

To study immunohistochemical expression of cytokeratin19 (CK19), galectin-3 (Gal-3) and HBME-1 in thyroid lesions and to assess their usefulness as markers in the differential diagnoses of thyroid nodular lesions.. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue of 21 cases of nodular goiters, 14 cases of toxic goiters, 15 cases of follicular adenomas (FA), 13 cases of follicular carcinomas (FC), 13 cases of follicular variant papillary carcinomas (FVPC) and 48 cases of classic papillary carcinomas (CPC).. All three markers were expressed in the cytoplasm with no or weak expression in benign lesions and diffuse and strong in malignant cases. Positive expressions of CK19, Gal-3 and HBME-1 were present in 11of 21, two of 21, four of 21 in nodular goiters, seven of 14, one of 14, one of 14 in toxic goiters, nine of 15, two of 15, two of 15 in FA, 10 of 13, eight of 13, seven of 13 in FC, 13 of 13, 11 of 13, 12 of 13 in FVPC, and 48 of 48, 45 of 48, 46 of 48 in CPC. The expression rates of the three markers between benign lesions (nodular goiters, toxic goiters and FA) and malignant lesions (FA, FVPC and CPC) were statistically significant. Among the three follicular lesions (FA, FC and FVPC), the differences were statistically significant as well. Nine, seven and six cases were negative for all three markers in nodular goiters, toxic goiters and FA, respectively. Only one case in FC was negative for all three markers, no case was all negative in FVPC and CPC; the rate of one case with two or more positive marker expression in nodular goiters, toxic goiters, FA, FC, FVPC and PC was 14.2% (3/21), 21.43% (3/14), 20.0% (3/15), 69.2% (9/13), 92.3% (12/13), 100.0% (48/48), the differences between benign lesions and malignant lesions and between FA, FC and FVPC were also statistically significant.. Immunohistochemical stains of CK19, Gal-3 and HBME-1, especially when used in combination, can be an important adjunct to the histopathological diagnoses of thyroid lesions.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Galectin 3; Goiter, Nodular; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms; Thyroid Nodule

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characterized the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma; Cell Count; Gallbladder Neoplasms; Hospitals, University; Humans; Immunoenzyme Techniques; Keratins; Mucins; Phenotype; Survival Rate

Sialadenoma papilliferum (SP) is a rare benign tumour of salivary gland origin, which has been included among the ductal papillomas in the latest classification of tumours by the World Health Organisation. Two SP from the minor salivary gland of the palate of middle age patients were presented and studied by immunohistochemical. Our results showed presence of cytokeratins (CKs) 13, 14, 7, 8, 19 and absence of vimentin and smooth muscle actin. This immunoprofile is similar to the excretory duct of salivary gland.

Topics: Adenoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Palatal Neoplasms; Palate, Hard; Palate, Soft; Salivary Gland Neoplasms; Salivary Glands, Minor

Adenomas of the non-pigmented epithelium of the ciliary body are rare neoplasms and most of the studies are in the form of case reports. There are only 27 documented cases of acquired neoplasm of the non-pigmented ciliary epithelium (NPCE) reported in the English literature. In most reports, there was a clinical suspicion of melanoma and the diagnosis of NPCE adenoma was made on histopathological evaluation of the resected tissue. The entity has not been reported in the Pakistani population to date. This report describes a case of ciliary body adenoma of NPCE in a 27 year old Pakistani man. The histological and immunohistochemical profiles were typical of the adenomas described in the literature.

Topics: Adenoma; Adult; Ciliary Body; Coloring Agents; Diagnosis, Differential; Eye Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Pakistan; S100 Proteins; Vimentin

Solid cell nests of the thyroid are embryonic remnants of endodermal origin that may be difficult to distinguish from squamous metaplasia, metastatic squamous carcinoma, papillary microcarcinoma, medullary carcinoma, and C-cell hyperplasia. These embryonic structures are composed of main cells and C-cells; cystic structures and mixed follicles are sometimes observed intermingled with solid cell nests. Recently, p63, a p53 homologue that is consistently expressed in basal/stem cells of stratified epithelia and plays a major role in triggering the differentiation of some specific cell lineages, has been characterized. We evaluated the immunohistochemical expression of p63, cytokeratins (CAM 5.2, AE1/AE3, 34betaE12, 7, and 20), carcinoembryonic antigen, thyroid transcription factor 1 (TTF-1), thyroglobulin, and calcitonin using the streptavidin-biotin-peroxidase complex technique in 6 bona fide solid cell nests. We observed that main cells of solid cell nests are strongly decorated by p63, while C-cells and all other thyroid structures were consistently negative. Moreover, main cells expressed carcinoembryonic antigen and all cytokeratins but cytokeratin 20 and lacked TTF-1, thyroglobulin and calcitonin. In contrast to this, C-cells of solid cell nests were immunoreactive for calcitonin, CAM 5.2, AE1/AE3, and cytokeratin 7; focal immunoreactivity for TTF-1 was also observed in some C-cells. We conclude that main cells of the solid cell nests display a basal/stem cell phenotype (p63 and basal cytokeratin positivity), whereas C-cells show features of parafollicular differentiation. We conclude, furthermore, that p63 antibodies may help in distinguishing solid cell nests from their mimics.

Topics: Adenoma; Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Papillary; DNA-Binding Proteins; Female; Genes, Tumor Suppressor; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Phosphoproteins; Stem Cells; Thyroid Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Nodal staging accuracy is important for prognosis and selection of patients for chemotherapy. Sentinel lymph node (SLN) mapping improves staging accuracy in breast cancer and melanoma and is being investigated for colorectal carcinoma.. To assess pathologic aspects of SLN staging for colon cancer.. Sentinel lymph nodes were identified with a dual surgeon-pathologist technique in 51 colorectal carcinomas and 12 adenomas. The frequency of cytokeratin (CK)-positive cells in mesenteric lymph nodes, both SLN and non-SLN, was determined along with their immunohistochemical characteristics.. The median number of SLNs was 3; the median number of total nodes was 14. The CK-positive cell clusters were detected in the SLNs of 10 (29%) of 34 SLN-negative patients. Adjusted per patient, SLNs were significantly more likely to contain CK-positive cells than non-SLNs (P <.001). Cell clusters, cytologic atypia, and/or coexpression of tumor and epithelial markers p53 and E-cadherin were supportive of carcinoma cells. Single CK-positive cells only, however, could not be definitively characterized as isolated tumor cells; these cells generally lacked malignant cytologic features and coexpression of tumor and epithelial markers and in 2 cases represented mesothelial cells with calretinin immunoreactivity. Colorectal adenomas were associated with a rare SLN CK-positive cell in 1 (8%) of 12 cases.. Sentinel lymph node staging with CK-immunohistochemical analysis for colorectal carcinomas is highly sensitive for detection of nodal tumor cells. Cohesive cell clusters can be reliably reported as isolated tumor cells. Single CK-positive cells should be interpreted with caution, because they may occasionally represent benign epithelial or mesothelial cells.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Colectomy; Colorectal Neoplasms; Databases, Factual; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Sentinel Lymph Node Biopsy

To study the expression of cytokeratin 19 (CK-19), HBME-1 and Ret in follicular-patterned thyroid tumors, and their significance for the diagnosis of the follicular variant of papillary thyroid carcinoma.. 111 well-differentiated follicular tumors were examined by immunohistochemistry: 59 papillary carcinomas (43 of the follicular variant), 40 follicular adenomas (among which 11 atypical adenomas), 10 oxyphil cell tumors and 2 follicular carcinomas.. CK-19 was diffusely expressed in all the papillary carcinomas, and was also expressed in 2/4 oxyphil cell carcinomas and 4/11 atypical adenomas. 90% of the follicular adenomas (26/29), the six oxyphil cell adenomas and the two follicular carcinomas showed at best a focal staining of dystrophic areas. 78% of the papillary carcinomas and 3/11 atypical adenomas were stained with HBME-1, whereas 26/29 adenomas (90%) and the 10 oxyphil cell tumors were negative. 34% of the papillary carcinomas expressed Ret (most of them were of the usual type (14/20)). The staining was often weak and focal (13/20). The other tumors were all negative for Ret.. CK-19 is a sensitive (100%) and specific (82.5%) marker of papillary carcinomas, which can be helpful in the diagnosis of its follicular variant. HBME-1 can improve this specificity when associated with CK-19. The Ret protein expression is of limited practical interest.

Topics: Adenoma; Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Drosophila Proteins; Humans; Immunohistochemistry; Keratins; Oxyphil Cells; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Thyroid Neoplasms

M cells are found in intestinal follicle associated epithelium. Studies into the physiological and pathological roles of human M cells have been hampered by the lack of well-substantiated, specific markers for these cells. A critical literature review suggests the following molecules may potentially serve as such markers: CK7, FcaR (CD89), S100, CD1a, CD21, CD23, sialyl Lewis A, and cathepsin E. Normal ileum, appendix and colorectum were studied using paraffin-embedded, formalin-fixed tissue and immunohistochemistry for these 8 markers. Cathepsin E immunohistochemistry was also performed on cases of colorectal adenocarcinoma, colorectal adenoma, colorectal hyperplastic/metaplastic polyp, lymphocytic colitis, collagenous colitis, pseudomembranous colitis and active ulcerative colitis. Of the 8 markers tested, only cathepsin E appeared to be specific to follicle associated epithelium (expressed by cells with and without M cell morphology) and follicular crypt epithelium; this specificity was limited to the colorectum. Focal epithelial expression of cathepsin E was seen in adenocarcinoma, adenoma, hyperplastic/metaplastic polyp, ulcerative colitis and pseudomembranous colitis. In conclusion, cathepsin E is a specific marker of normal colorectal follicle associated epithelium and follicular crypt epithelium though is not specific to M cells within these compartments. None of the other 7 markers studied is exclusively expressed by human M cells.

Topics: Adenocarcinoma; Adenoma; Biomarkers; CA-19-9 Antigen; Cathepsin E; Colitis; Colorectal Neoplasms; Epithelial Cells; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Keratin-7; Keratins; Lower Gastrointestinal Tract; Peyer's Patches

Immunohistochemistry is an important tool when dealing with salivary gland neoplasms. Canalicular adenoma and polymorphous low-grade adenocarcinoma may share some histologic characteristics that can cause difficulties in their separation. In the present study, cases of polymorphous low-grade adenocarcinoma and canalicular adenoma were submitted to a panel of antibodies to evaluate the differences in their immunoprofiles. The results obtained showed that, while vimentin is only expressed by polymorphous low-grade adenocarcinoma, CK7 and CK8 are present in both neoplasms. Therefore, vimentin is the best marker to differentiate between these tumors.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratin-7; Keratins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

Basal cell adenoma is an uncommon epithelial neoplasm of the salivary gland most commonly arising in the parotid glands. We report a case of basal cell adenoma of the minor salivary gland presenting as a slowly progressing, large parapharyngeal mass. Histopathology revealed a well-encapsulated mass with characteristic histomorphology. Immunohistochemistry showed selective positivity for pancytokeratin, S-100, and smooth muscle actin in the tumor which highlighted the participation of myoepithelial cells in histogenesis. In addition, positivity was noted for carcinoembryonic antigen and vimentin. Ultrastructural analysis showed characteristic features including reduplicated basal laminae around the tumor cells, presence of intermediary filaments, and rough endoplasmic reticulum in the cytoplasm. There are no reports of basal cell adenoma presenting as a parapharyngeal mass lesion in the available English literature. This case highlights the rarity of this tumor with regard to its site of origin, possibly from a minor salivary gland.

Topics: Actins; Adenoma; Biomarkers, Tumor; Cytoplasmic Structures; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neck; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Tomography, X-Ray Computed; Treatment Outcome

A retrospective study was conducted in order to elucidate the clinicopathological significance of fibrous bodies, a hallmark of the sparsely granulated variant of GH-producing pituitary adenomas.. A total of 37 acromegalic patients, 14 men and 23 women, with pure GH adenomas were studied. Immunohistochemistry was performed with antibodies specific for cytokeratin 8 and 18 (CAM5.2), GH, prolactin and E-cadherin. The tumour volume was estimated with high-resolution magnetic resonance imaging.. The percentages of adenoma cells with dot-like immunoreactivity for CAM5.2, fibrous bodies, were variable, ranging continuously from 0 to 100%. An increased percentage was associated with a lower basal GH level per unit tumour volume, a lower GH response to a bromocriptine suppression test, decreased immunoreactivities for GH and prolactin, and a decreased expression of E-cadherin immunoreactivity.. GH adenomas could not be distinctly separated into those with or without fibrous bodies. Decreased expression of E-cadherin may be involved in formation of fibrous bodies and result in lower GH production.

Topics: Adenoma; Adult; Aged; Biomarkers; Bromocriptine; Cadherins; Female; Growth Hormone; Hormone Antagonists; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Retrospective Studies

Nephrogenic adenoma is a rare benign lesion of the urinary tract involving mainly the urinary bladder. The clinical manifestations, endoscopic signs and histopathological pattern of NA should be differentiated from a cancer, which may be a source of misinterpretation. Here we report a case of a 70-year-old man previously treated for papillary urothelial carcinoma. Six months later he developed a tumour, giving rise to a suspicion of recurrence. Histopathologically the tumour was diagnosed as nephrogenic adenoma. It is the first case of nephrogenic adenoma in Polish literature.

Topics: Adenoma; Aged; Antigens, Nuclear; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Second Primary; Nuclear Proteins; Treatment Outcome; Urinary Bladder Neoplasms; Vimentin

We applied monoclonal antibodies against RET and cytokeratin 19 (CK19) to the following tumor sections: classic papillary carcinoma (PC), 16; Hürthle-type PC (HPC), 1; sclerosing PC with nodular fasciitis-like stroma (SPC), 1; PC, follicular variant (FVPC), 12; follicular adenoma (FA), 9; Hürthle cell adenoma (HA), 4; Hürthle cell carcinoma (HC), 3; and follicular carcinoma (FC), 7. CK19+ tumors included 16 PCs, 1HPC, 1SPC, 11 FVPCs, 7 FAs, 4 FCs, and 1HC. RET+ tumors included 4 HAs, 3 HCs, 1HPC, 12 PCs, 7 FVPCs, and 2 FAs. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a RET transcript in 6 Hürthle cell lesions. RET immunoreactivity is less sensitive and specific for PC than CK19. CK19 is useful for identifying PC, although only lesions with diffuse, intense staining should be considered positive. The detection of RET protein by immunohistochemical analysis was corroborated by the presence of the RET transcript by RT-PCR. Further study is warranted to determine whether this represents activation by gene fusion or some other mechanism in this subset of thyroid neoplasms.

Topics: Adenocarcinoma, Follicular; Adenoma; Adenoma, Oxyphilic; Antibodies, Monoclonal; Artificial Gene Fusion; Carcinoma, Papillary; Drosophila Proteins; Humans; Keratins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Thyroid Neoplasms; Transcription, Genetic

A histopathological and immunohistochemical study of a case of nephrogenic adenoma of the bladder associated to glandular cystitis is presented with a very similar immunostaining to adenomatoid tumors in other organs and probably of a mesothelial origin. Its pathogenesis seems to correspond to a metaplastic change of the bladder's urothelium through anomalous differentiation of the reserve cells faced with different irritating agents. Because of its benign characteristics, we think that treatment can be confined to endoscopic observation and conservative technique.

Topics: Adenoma; Aged; Biomarkers, Tumor; Carcinoma; Cystitis; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Metaplasia; Mucin-1; Neoplasm Proteins; Urinary Bladder Neoplasms; Urography; Urothelium; Vimentin; von Willebrand Factor

Eleven cases of metanephric adenoma are reported. The tumors were selected out of 6500 tumorous and pseudotumorous lesions of the kidney in our registry. Female to male ratio was 1:1.2. The average age of the patients was 48.3 years, with a range of 13-79 years. The mean size of the tumors was 7.2 cm. The tumors were spherical in shape, whitish to yellowish in colour. Histologically, they were arranged in a mainly tubular pattern with short pseudopapillae. The tumorous cells were deeply eosinophilic to basophilic with predominantly round nuclei. Psammomatous bodies were numerous. Immunohistochemically, they reacted positively with antibodies against cytokeratins, vimentin, and WT1. Ultrastructurally, the cytoplasm contained mitochondria, RER, and ribosomes. A collagenous spherulosis, identical with those in salivary gland and mammary tumors, was revealed in one case. The spherules were located mainly inside tubular structures. Ultrastructurally, they were composed of basement membrane-like material, which was surrounded by epithelial cells. Follow-up all of our patients was negative (if known) for 10 months to 4 years.

Topics: Adenoma; Adolescent; Adult; Aged; Collagen; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin; WT1 Proteins

Corticotroph adenomas rarely show Crooke's hyaline change in neoplastic cells, a feature similar to that of normal corticotroph cells exposed to excess cortisol. Crooke's cell adenomas are usually associated with Cushing's disease. Nonfunctioning examples are uncommon. We report two clinically silent corticotroph adenomas featuring extensive Crooke's hyalinization in neoplastic cells. The two patients were 49 and 59 yr of age and neither had Cushing's disease. Serum and urinary cortisol were normal. One patient had elevated serum adrenocorticotropic hormone. In our experience, the two patients accounted for 0.4% of pituitary adenomas operated on from January 1992 to December 2001 and 3.5% of all corticotroph adenomas. The two lesions had features of the subtype 1 silent corticotroph adenoma. Cytogenetic analysis performed on one lesion showed a normal karyotype (46;XY). Hyalinization in clinically silent Crooke's cell adenoma indicates that hyaline changes do not always relate to excess cortisol. It is known that neoplastic Crooke's cells show immunoreactivity for glucocorticoid receptors stronger than nontumorous Crooke's corticotrophs. This fact suggests that receptor overexpression or lack of receptor downregulation may result in hypersensitivity of neoplastic Crooke's cells to physiologic cortisol plasma levels.

Topics: Adenoma; Adrenocorticotropic Hormone; Female; Humans; Hyalin; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Male; Middle Aged; Pituitary Gland, Anterior; Pituitary Neoplasms; Treatment Outcome

Spontaneous basaloid adenomas occurred in four out of 354 dogs with mammary tumors. Affected dogs were pure-bred, intact females between 6 and 8 years of age. Three dogs were nuliparous, two had pseudopregnancies, and none had received contraceptive steroids. The tumors were multiple (three cases) or unique, less than 1 cm in diameter, well delineated, and composed of uniform cords and clusters of monomorphic epithelial cells with focal signs of squamous or glandular differentiation. A basal cell immunophenotype (cytokeratins 5 and 14 positive) without either glandular epithelial (cytokeratins 8, 18, and 19 negative) or myoepithelial (calponin negative) differentiation was observed in the majority of tumor cells. No recurrence or metastasis was recorded after follow-up periods between 3 and 24 months. In spite of the hormone-dependent nature of this tumor in female Beagles given experimental contraceptive steroids, spontaneous basaloid adenomas lacked estrogen receptor alpha and progesterone receptors.

Topics: Adenoma; Animals; Calcium-Binding Proteins; Calponins; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Microfilament Proteins

Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also up-regulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computer-assisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).

Topics: Adenoma; Carcinoma; Disease Progression; Galectins; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Gland; Thyroid Neoplasms

Topics: Adenoma; Adult; Biopsy; Colonic Diseases; Colonic Neoplasms; Colonoscopy; Diagnosis, Differential; Endometriosis; Female; Humans; Keratins; Magnetic Resonance Imaging

Topics: Actins; Adenoma; Antigens, CD34; Biomarkers, Tumor; Diagnosis, Differential; Female; Focal Nodular Hyperplasia; Hepatocytes; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Middle Aged; Precancerous Conditions

Carcinoid tumors and adenomas of the middle ear are rare neoplasms of indeterminate relationship to one another. Indeed, the literature is devoid of a large comprehensive series that evaluates the clinical, histologic, and immunophenotypic features of these tumors and their potential relationship. Forty-eight cases of middle ear adenoma between 1970 and 1995 were identified in the files of the Armed Forces Institute of Pathology. All cases were evaluated for cytomorphology and architectural pattern, in addition to their reactivity with various immunohistochemical reagents. Clinical follow-up was also obtained. A comprehensive review of the literature was performed with an eye toward correlating any distinct differences or similarities between carcinoid tumors and adenomas of the middle ear. The patients included 21 women and 27 men, aged 20 to 80 years (mean, 45.0 y). Patients experienced hearing loss, mass, and/or pain for a mean duration of 1.7 years. The mean tumor size was 0.8 cm, with six tumors extending beyond the middle ear. Histologically, the tumors were moderately cellular and unencapsulated, arranged in glandular, trabecular, and solid patterns composed of small cells with "salt and pepper" nuclear chromatin distribution. The tumor cells were immunoreactive with keratin, keratin 7, chromogranin, and human pancreatic polypeptide. All patients had surgery. No patients died with their disease (mean follow-up, 15.7 y). Eight patients developed recurrences that were treated surgically and were without evidence of disease at last follow-up (mean, 15.1 y). Our study and the review of the literature showed adenomas and carcinoid tumors of the middle ear to be essentially indistinguishable benign tumors. Middle ear adenoma most correctly describes their morphologic features and clinical behavior, although neuroendocrine adenoma of the middle ear may be a more accurate designation.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoid Tumor; Chromogranins; Diagnosis, Differential; Ear Neoplasms; Ear, Middle; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Review Literature as Topic; S100 Proteins; Treatment Outcome; Vimentin

To elucidate histological changes in the pituitary gland and adenomas following radiotherapy, two irradiated pituitary glands and seven irradiated non-functioning adenomas were studied. The latter included four cases with conventional radiation (CR) and three cases with radiosurgery: two with gamma knife radiosurgery (GKR) and one with stereotactic fractionated radiotherapy (SRT). The specimens were obtained 10 months to 10 years (mean 58 months) after the radiotherapy. Irradiated pituitary glands showed diffuse fibrosis in the adenohypophysis, whereas irradiated adenomas showed either mild or no fibrosis in five CR/SRT cases and diffuse thick hyaline deposits in two GKR cases. No necrosis was observed. Stellate-shaped S-100 protein-positive cells were greater in number in the irradiated pituitary glands than in the normal glands. Pituitary cells with dense granular reactivity for mitochondrial protein, cytochrome oxidase, and Mn-SOD, mimicking oncocytes, were greater in number in the irradiated adenohypophysis but did not show any change in cell size. Many irradiated pituitary cells and some irradiated adenoma cells were densely positive with anticytokeratin 1,5,10,14 antibody whereas non-irradiated counterparts were negative. In adenomas, MIB-1 labeling index remained unchanged after the radiation. The results may indicate that radiation-induced fibrosis was associated with an increased number of folliculo-stellate cells, mitochondrial dysfunction, and squamous metaplasia. These findings were prominent in irradiated pituitary cells and may participate in delayed pituitary hypofunction following radiotherapy. In irradiated adenoma cells, similar findings were observed but diffuse fibrosis was absent. The histological changes were more intensive in adenomas following GKR than those following CR.

Topics: Adenoma; Aged; Antibodies, Antinuclear; Antibodies, Monoclonal; Female; Fibrosis; Humans; Hypopituitarism; Keratins; Male; Pituitary Gland, Anterior; Pituitary Irradiation; Pituitary Neoplasms; Radiosurgery; S100 Proteins; Superoxide Dismutase

We report a case of an aggressive digital papillary adenocarcinoma (ADPA) on the right thumb of a 48-year-old white man. Histologic evaluation of the initial biopsy demonstrated features consistent with those proposed for aggressive digital papillary adenoma; however, re-excision of the remaining lesion revealed histologic features consistent with aggressive digital papillary adenocarcinoma. These tumors have a high rate of local recurrence and can metastasize, occasionally resulting in mortality. Our case demonstrates that even if the histologic criteria of aggressive digital papillary adenocarcinoma are met, the lesion may still represent an aggressive digital papillary adenocarcinoma (ADPAca). In agreement with a recent study by Duke et al., this case supports the idea that aggressive digital papillary lesions should be classified as aggressive digital papillary adenocarcinoma.

Topics: Adenocarcinoma, Papillary; Adenoma; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sweat Gland Neoplasms; Thumb

Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Those cells may be distributed in various arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is also a benign neoplasm composed by columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. There is some disagreement among investigators about whether canalicular adenoma should be included within the basal cell adenoma histologic spectrum. In the present study we compared the expression of cytokeratins (CK), vimentin and muscle-specific actin, utilizing immunohistochemical technique, in three cases diagnosed as basal cell adenomas predominantly of the solid type, and three cases of canalicular adenomas. The results obtained showed a distinct immunoprofile for both neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested antibodies; only when there was tubular differentiation, those structures expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13. The panel of antibodies utilized supports the separation of the two entities.

Topics: Actins; Adenocarcinoma; Adenoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasm Proteins; Salivary Gland Neoplasms; Vimentin

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.

Topics: Actins; Adenocarcinoma; Adenoma; Adult; Aged; Carcinoembryonic Antigen; Cell Division; DNA, Neoplasm; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Invasiveness; Prognosis; Receptor, ErbB-2; Retrospective Studies; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Survival Rate; Tumor Suppressor Protein p53; Vimentin

The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures.. Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis.. The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.

Topics: Adenoma; Adult; Antigens, Nuclear; Biomarkers, Tumor; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nuclear Proteins; Thyroid Neoplasms

To assess the potential value of cytokeratins (CK) 8,18,19 as tumor markers for thyroid diseases, a study was performed comparing serum CK 8,18,19 levels in patients affected from thyroid carcinoma, adenoma, other benign thyroid diseases and healthy volunteers as controls. One hundred cases (65 patients and 35 controls) were examined. Thirty patients had thyroid carcinoma (18 papillary--PTC, 8 follicular--FTC, 4 medullary--MTC), 19 non-toxic goiter, 10 thyroid adenoma, 6 chronic thyroiditis and 35 healthy volunteers as controls. These controls were matched by age and sex. The mean value of CK in benign thyroid diseases (46.1 U/L) was significantly higher (p<0.02) than that in healthy controls (29.6 U/L). The mean value of CK in carcinomas (68.1 U/L) was significantly higher than that in healthy controls (p<0.01) and benign thyroid diseases patients (p<0.05). The positive rate of CK in thyroid carcinomas was 28.1%, while in benign thyroid diseases was 17.8%. The CK sensitivity for thyroid carcinomas was 28.1%, with a specificity of 80% and accuracy of 70.4%. In PTC patients the mean CK value was not significantly higher than in the benign diseases' group and in healthy subjects. No evident correlation between CK levels and tumor mass was found. In FTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects. Large tumors showed the highest levels, while small tumor values were similar to the control ones. In MTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects, with the highest peaks in large tumors and metastatic tumors. The detection of increased values in thyroid carcinomas with high metastatic potential (FTC and MTC) seems to confirm the role of these antigens in predicting the malignancy's degree of the neoplasm. These findings, if confirmed in larger series, could play an important role in assessing the CK 8,18,19 serum level as a real prognostic factor. Further repeated serum determinations after total thyroidectomy might indicate the role of CK 8,18,19 as serum markers predicting the risk of metastases.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Medullary; Carcinoma, Papillary; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Thyroid Neoplasms

Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Pathology; Thyroid Neoplasms; Thyroid Nodule

To evaluate the expression of cytokeratin (CK) 19, we stained sections obtained from formalin-fixed, paraffin tissue blocks of 35 thyroid tumors (follicular adenoma [FA], 20; papillary thyroid carcinoma [PTC], 10 follicular variant [FV] and 5 usual type) and scored the extent of staining as follows: 1+ (<5% positively stained cells), 2+ (5%-25% positively stained cells), 3+ (25%-75% positively stained cells), and 4+ (>75% positively stained cells). All 15 PTCs (including 10 FV-PTCs) were CK19 positive: 14 were 4+ and 1 (FV-PTC) was 2+. All 20 FAs also were CK19 positive: 15 were 1+, 1 was 2+, 4 were 3+, and none was 4+. In the FAs that were scored 1+, reactivity usually was confined to follicular cells lining cystically dilated atrophic follicles that lacked the typical nuclear features of PTC. The remaining FAs showed more diffuse reactivity, which was, however, less intense than that observed in the PTCs. Thus, immunoreactivity for CK19 is not specific for PTC, although we acknowledge that the extent and intensity of staining are considerably greater in this tumor than in FA. There were no significant differences in staining for CK19 between nonneoplastic follicles adjacent to PTCs and those adjacent to FAs.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Cell Count; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Pathology; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.

Topics: Adenoma; Breast Diseases; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chromosome Aberrations; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; In Situ Hybridization, Fluorescence; Keratins; Molecular Weight; Nucleic Acid Hybridization; Papilloma, Intraductal; Precancerous Conditions

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Fluorescent Antibody Technique, Direct; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

We report a case of asymptomatic mesoblastic nephroma in a 54-year-old woman. The tumor showed immunohistochemical reactions similar to developing nephrons. Electron microscopy showed immature tubules with numerous intracytoplasmic intermediate filaments. Recent studies support the concept of pathogenesis of the mesoblastic nephroma originating from collecting ducts. However, this case exhibited a complex pattern of antigenic expression not restricted to the collecting ducts, but including the glycoprotein CD24 and the neural cell adhesion molecule (NCAM). The following differential diagnoses will be discussed: benign mixed epithelial and stromal tumor, metanephric adenoma, and nephrogenic adenofibroma.

Topics: Adenofibroma; Adenoma; Antigens, CD; Biomarkers, Tumor; CD24 Antigen; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratin-7; Keratins; Kidney Neoplasms; Membrane Glycoproteins; Middle Aged; Neoplasms, Complex and Mixed; Neoplasms, Glandular and Epithelial; Nephroma, Mesoblastic; Neural Cell Adhesion Molecules; Tomography, X-Ray Computed

Hale's colloidal iron staining of 8 chromophobe cell carcinomas (CCC) was compared with that of non-chromophobe renal cell carcinomas (RCC), renal oncocytomas, and renal adenomas. Six non-chromophobe RCC showing diffuse and moderate cytoplasmic staining contained extensive areas with translucent cytoplasm as observed in CCC. Seventeen of 25 conventional RCC of the clear cell variant (randomly chosen from 130 cases), 21 of 26 RCC with areas of chromophilic cytoplasm, and 16 of 20 papillary RCC, 7 of 14 adenomas and 14 of 16 oncocytomas displayed focal areas with mild to moderate staining of the cytoplasm. Hale's colloidal iron staining was partially reduced by digestion with neuramidase but not with hyaluronidase. This positive staining demonstrated glycoproteins containing sialylated glycoconjugates, probably a type of acid epithelial mucin. We suggest that there is a spectrum of mucin-like changes in typical CCC representing RCC with extensive and marked "mucin-like changes". The eosinophilic variant of CCC and some RCC with extensive chromophobe cell features represent renal neoplasms with moderate changes. The other RCC, oncocytomas and papillary renal neoplasms with mild to moderate staining with Hale's colloidal iron represent renal neoplasms with focal mucin-like changes. RCC with extensive chromophobe cell features may pose a differential diagnostic problem with CCC.

Topics: Adenocarcinoma; Adenoma; Adenoma, Oxyphilic; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Iron; Keratins; Kidney Neoplasms; Mucin-1; Neoplasm Proteins; Neuraminidase; Vimentin

It has recently been suggested that hyalinizing trabecular adenoma of the thyroid is an encapsulated variant of papillary carcinoma because of certain similarities of their histology, the occasional occurrence of both tumors in the same gland, and their similar pattern of expression of cytokeratins, including staining for cytokeratin 19. To investigate this notion further, we examined immunocytochemically the expression of a series of cytokeratins in 12 hyalinizing trabecular adenomas and six papillary carcinomas. Hyalinizing trabecular adenoma showed no or minimal reactivity for cytokeratin 19, whereas papillary carcinoma was almost always strongly reactive. Also, hyalinizing trabecular adenoma showed no staining for high-molecular-weight (HMW) cytokeratin, whereas papillary carcinoma was strongly positive. Thus, there are different patterns of cytokeratin 19 and HMW cytokeratin expression in hyalinizing trabecular adenoma and papillary carcinoma. The findings do not support the suggestion that hyalinizing trabecular adenoma is an encapsulated variant of papillary carcinoma.

Topics: Adenoma; Adult; Aged; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Staining and Labeling; Thyroid Neoplasms

Thyroid transcription factor-1 (TTF-1), a member of the NKx2 family of homeodomain transcription factors, is a mediator of thyroid-specific transcription of the thyroglobulin (TG) gene. The combined immunohistochemical profile of TTF-1, TG, cytokeratin 7 (CK7), and cytokeratin 20 (CK20) in neoplasms of the thyroid gland and their metastases to other sites has not been defined previously. Formalin-fixed tissue of 43 thyroid tumors, including 31 carcinomas and 12 adenomas, and 16 metastasic lesions were immunostained using monoclonal antibodies to TTF-1, TG, CK7, and CK20. Immunoreactivity of the primary tumors (adenomas and carcinomas) for TTF-1 was seen in 32 cases (74%), TG 32 (74%), and CK7 34 (79%), whereas none (0%) showed positivity for CK20. The distribution of reactivity in the 31 carcinomas for TTF-1, TG, and CK7, respectively was papillary (8/8), (8/8), and (8/8); poorly differentiated (6/7), (4/7), and (6/7); oncocytic (Hürthle) cell (2/6), (6/6), and (4/6); follicular (4/4), (3/4), and (3/4); medullary (1/2), (0/2), and (1/2). One of four anaplastic carcinomas was focally immunoreactive showing positivity for TTF-1 only. Of the six follicular adenomas, five were positive for TTF-1, six for TG, and six for CK7. Among the six oncocytic cell adenomas, five were reactive for TTF-1, five for TG, and all six for CK7. Twelve (75%) of the 16 metastatic tumors were positive for TTF-1, 10 (63%) for TG, 15 (94%) for CK7, and none (0%) for CK20. In summary, TTF-1 and TG are demonstrable by immunohistochemistry in the majority of thyroid neoplasms. Compared with TG, an antibody to TTF-I is a similarly sensitive marker for thyroid tumors. Moreover, TTF-1 is a more sensitive marker for poorly differentiated carcinomas and metastasis. In most cases, its nuclear pattern of immunoreactivity facilitates interpretation. Thyroid tumors are CK7+/CK20-. The panel of antibodies for TG, TTF-1, CK7, and CK20 is useful when the thyroid origin of a metastatic tumor is a consideration.

Topics: Adenoma; Carcinoma; Humans; Immunohistochemistry; Keratins; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

A panel of antibodies composed of the cytokeratins (CKs), vimentin, and actin was applied to 114 minor salivary gland tumors to evaluate its diagnostic value. The results revealed that luminal cells of intercalated duct-like structures, such as those seen in pleomorphic adenoma, basal cell adenoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, expressed CKs 7, 8, 14, and 19. The outer cells of these structures exhibited vimentin or vimentin plus muscle-specific actin, but rarely CK14, which is seen particularly in pleomorphic adenoma, in the tubular type of basal cell adenoma, and seldom in the tubular type of adenoid cystic carcinoma. Modified myoepithelial cells of pleomorphic adenoma and myoepithelioma exhibited a variable immunoprofile. CKs 7 and 8 were also observed in acinar cell adenocarcinoma and polymorphous low-grade adenocarcinoma with vimentin in the latter. CK13 was expressed only by canalicular adenoma and mucoepidermoid carcinoma cells. This study showed that the panel of antibodies employed is effective in distinguishing among salivary gland tumors.

Topics: Actins; Adenocarcinoma; Adenoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Immunohistochemistry; Keratins; Myoepithelioma; Salivary Gland Neoplasms; Vimentin

The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 produced during apoptosis. It is reactive in formalin-fixed, paraffin-embedded tissue and has great potential in the study of apoptosis in clinical and experimental material.. To compare the results of M30 immunoexpression with a more established technique of demonstrating apoptosis in tissue sections, in situ end-labeling. A secondary objective was to compare the results with immunoexpression of the proliferation-associated antigen Ki-67.. Retrospective analysis of adenomas and adenocarcinomas of the large intestine.. Immunohistochemistry for M30 and Ki-67, and in situ end-labeling. Formalin-fixed, paraffin-embedded tissue was used.. The number of cells positive for M30, Ki-67, and in situ end-labeling, expressed as a proportion of the total number of cells counted.. A strong positive correlation was found between in situ end-labeling and expression of M30, although the counts were widely scattered around the regression line. Counts of Ki-67 were strongly correlated with both M30 expression and in situ end-labeling. Immunoexpression of M30 was generally easier to interpret than in situ end-labeling, and the procedures for M30 immunohistochemistry were technically less exacting.. These findings support the application of M30 immunoreactivity in the study of apoptosis.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Apoptosis; Immunohistochemistry; In Situ Nick-End Labeling; Intestinal Neoplasms; Intestine, Large; Keratins; Ki-67 Antigen; Statistics as Topic

We report a unique case of a salivary gland type of "hybrid carcinoma" arising within a Bartholin's gland adenoma. The tumor was characterized by large areas of an epithelial-myoepithelial carcinoma similar to that of the salivary gland with a peripheral infiltrative pattern of an adenoid cystic carcinoma (ACC).

Topics: Adenoma; Bartholin's Glands; Biopsy; Carcinoma, Adenoid Cystic; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Middle Aged; Neoplasms, Multiple Primary; S100 Proteins; Salivary Gland Neoplasms; Vulvar Neoplasms

We report a case of middle ear adenoma, a rare epithelial tumour composed of adenomatous and neuroendocrine cells. These tumours have been designated by many different names, leading to controversy regarding their histogenesis and classification. The diagnosis was based on light microscopy and immunohistochemistry. A positive immunoreaction was evidenced for antibodies to keratin and chromogranin. The tumour was removed surgically. No additional therapy is recommended in the literature.

Topics: Adenoma; Chromogranins; Ear Neoplasms; Ear, Middle; Humans; Keratins; Male; Middle Aged

A unique case of metanephric adenoma of the left kidney is reported in a 61-year-old woman presenting with an incidental renal mass on ultrasonography.. On radiographic examination, the presence of hypovascular renal cell carcinoma was suspected and left radical nephrectomy was performed. The resected tumor, measuring 4.9 x 4.7 x 4.5 cm, was well-circumscribed and solid and its cut surface was tan-pink with foci of focal hemorrhage and cystic change. Microscopically, the tumor was composed of uniformly small acini with hyperchromatic round nuclei. Some acini were dilated and occasionally contained glomeruloid-like bodies and psamoma bodies. Immunohistochemically, tumor cells showed positive immunoreaction for vimentin, cytokeratin and Leu 7. Cytogenetically, the tumor did not show numerical aberrations of chromosome 7 or 17 by fluorescence in situ hybridization.. The patient is alive without recurrence or metastasis 4 years after surgery. Metanephric adenoma must be differentiated from other renal tumors, particularly Wilms' tumor or low-grade renal cell carcinoma. Immunohistochemical and cytogenetic analysis may be helpful in difficult cases.

Topics: Adenoma; Biomarkers, Tumor; Cytogenetics; DNA, Neoplasm; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Kidney; Kidney Neoplasms; Magnetic Resonance Imaging; Middle Aged; S100 Proteins; Tumor Suppressor Protein p53; Vimentin

Eight hepatic atypical adenomatous hyperplasias (AH), 30 hepatocellular carcinomas (HCC) consisting of 11 well-, 13 moderately and six poorly differentiated HCC, and 10 intrahepatic cholangiocarcinomas (CC) were investigated immunohistochemically with anti-alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9, epithelial membrane antigen (EMA), and cytokeratins (CK) 18 and 19 antibodies. Immunostaining was regarded as positive when more than 5% of cells were stained. Alpha-fetoprotein was positive, although focally, in five (17%) of 30 HCC but negative in all AH and CC. Carcinoembryonic antigen (polyclonal antibody) did not stain the cytoplasm of all AH and HCC, but stained two (25%) of eight AH and 10 (33%) of 30 HCC in a bile canalicular staining manner. Carcinoembryonic antigen showed intracytoplasmic or luminal border staining in six (60%) of 10 CC. CA19-9 was negative in all AH and HCC, while six (60%) of 10 CC were positive for CA19-9. Epithelial membrane antigen was positive in one (13%) of eight AH, seven (23%) of 30 HCC and in all 10 cases of CC. Cytokeratin 18 was positive in all AH, HCC and CC. Cytokeratin 19 was negative in both AH and HCC, whereas it stained the cytoplasm of tumor cells in all CC diffusely and intensely. These results suggest that immunostaining of AFP, CEA, CA19-9, EMA, CK18 and CK19 are not useful in the differential diagnosis between AH and well-differentiated HCC, and that CK19 is the most suitable reagent for the differential diagnosis between HCC and CC.

Topics: Adenoma; alpha-Fetoproteins; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Humans; Hyperplasia; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Mucin-1; Precancerous Conditions; Predictive Value of Tests; Prognosis

An acromegalic patient with a pituitary somatotroph adenoma associated with an extremely elevated plasma GHRH concentration is presented. The preoperatively high concentration of plasma GHRH returned to the normal level after successful removal of the adenoma. GHRH production and GHRH gene expression were confirmed in the adenoma by studies including immunohistochemistry and in situ hybridization. Expression of GHRH receptor messenger ribonucleic acid was verified by in situ hybridization. Immunohistochemical double staining for GH and GHRH revealed their colocalization in single adenoma cells. These findings confirmed the autocrine or paracrine regulation of GH production by endogenous GHRH from the adenoma cells. GHRH synthesis in the pituitary gland has recently been demonstrated, however, there have been no previous reports of a GHRH-producing pituitary somatotroph adenoma associated with an elevated plasma GHRH concentration. The existence of this GHRH-producing adenoma suggests a possible role of locally generated GHRH in the progression of somatotroph adenomas, i.e. the monoclonally established somatotroph adenomas develop further under the influence of locally produced GHRH. The demonstration of GHRH production by this somatotroph adenoma is of importance in clarifying the autocrine or paracrine regulation of GH production and the progression of human somatotroph adenomas.

Topics: Acromegaly; Adenoma; Adult; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Magnetic Resonance Imaging; Male; Microscopy, Electron; Pituitary Neoplasms; RNA, Messenger

Nephrogenic Adenoma (NA) is a rare lesion of the urinary tract, considered a metaplastic response to chronic inflammation, trauma or immunosuppression.. We report two cases of NA arising in the urinary bladder of patients with previous history of recurrent urinary tract infections due to neuropsychiatric disease. Pathological examination of the lesions, resected by transurethral (TUR) management, revealed a papillary proliferation of tubules and cysts lined by cuboidal to low-columnar cells without atypia. Immunohistochemistry showed positivity for Cam 5.2, CK7 and EMA. MIB 1 count demonstrated a positivity in 12/200 cells in case 1 and < 2/200 in case 2. No expression of nuclear p53 was evident.. NA is a benign unusual neoplasm which might be misdiagnosed as clear cell adenocarcinoma of the bladder or prostatic adenocarcinoma. Its recognition is important because it is a benign lesion cured by a conservative resection and no additional therapy is generally required.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Adenoma; Antigens, Nuclear; Biomarkers, Tumor; Calbindin 2; Carcinoma in Situ; Carcinoma, Transitional Cell; Diagnosis, Differential; Epithelial Cells; Female; Humans; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Metaplasia; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Multiple Primary; Nuclear Proteins; Prostatic Neoplasms; Protein Isoforms; S100 Calcium Binding Protein G; Urinary Bladder Neoplasms

We have previously shown that necrotic tumors retain their immunoreactivity for a range of cytokeratin antibodies. Some thyroid tumors undergo extensive necrosis after fine-needle aspiration (FNA) procedures. We evaluated the sensitivity of antibodies on necrotic thyroid tumors by examining a series of thyroid tumors consisting of 10 Hurthle cell neoplasms, 8 carcinomas, and 2 follicular adenomas (12 with post-FNA necrosis). These were stained with antibodies to AE1/3, PANCK, thyroglobulin and S100. Four of the cases of papillary carcinoma were also stained with antibodies to CK19. As a control for the specificity of thyroglobulin immunoreactivity in necrotic tissue, we also stained 11 nonthyroid tumors with extensive necrosis (7 carcinomas, 1 lymphoma, 2 melanomas, 1 sarcoma) for thyroglobulin. Six of 8 thyroid carcinomas were positive for AE1/3 and PANCK; AE1/3 reactivity was retained in necrotic areas of 4 of 6. AE 1/3 was positive in necrotic portions of 5 of 10 Hurthle cell lesions, whereas PANCKwas negative in all but 1. Thyroglobulin reactivity was present in 18 of 20 cases, and was preserved in necrotic portions of 5 of 6 carcinomas, as well as 8 of 10 Hurthle cell neoplasms. S100 cytoplasmic reactivity was present in 4 Hurthle cell neoplasms and 1 papillary carcinoma; this staining was lost in necrotic areas. No staining by thyroglobulin was observed in the viable or necrotic areas of nonthyroid neoplasms. The preservation of cytokeratin reactivity, measured by AE1/3, in thyroid neoplasms is a diagnostically useful feature in spontaneous and post-FNA infarction. PANCK is not a well-preserved marker in necrotic thyroid tissue. This difference may be due to detection of keratin 19 by AE1/3. Thyroglobulin is preserved in some necrotic thyroid carcinomas and in Hurthle cell lesions. Preservation of thyroglobulin reactivity in necrotic tissue is specific in that no staining was observed in nonthyroid neoplasms. These results suggest that thyroglobulin is useful in demonstrating thyroid lineage of both primary and metastatic necrotic tumor masses.

Topics: Adenoma; Adenoma, Oxyphilic; Carcinoma; Humans; Immunohistochemistry; Keratins; Necrosis; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

Uncertainty about the factors influencing phenotypes in salivary canalicular adenoma prompted the present investigation.. Specimens of canalicular adenoma from 15 patients were examined with the use of histology, histochemistry for protein, mucosubstances and pigments, nerve staining and immunocytochemistry for cytoskeleton components. The tumours consisted largely of simple cells lining tubules that were occasionally cystic or branching and budding, and were set in loose, vascular and often haemorrhagic stroma. Other phenotypes recognized were mucous cells, apocrine-like cells, pigmented cells, microliths and stromal macrophages, detected in 26.6%, 20%, 33.3%, 20% and 53. 3% of the patients, respectively. Simple cells showed moderate levels of -SH groups and strong immunoreactivity for 'simple' epithelial phenotype cytokeratin. The simple cells lining cystic tubules showed additional immunoreactivity for 'stratified' epithelial phenotype cytokeratin, possibly an adaptation to mechanical pressure. Lumina showed variable levels of neutral and carboxylated glycoproteins, and chondroitin sulphate. Stroma showed high levels of chondroitin sulphate and hyaluronic acid. Mucous cells showed high levels of -SS- groups and nonsulphated glycoproteins. Apocrine-like cells contained lipofuscin. Pigmented cells contained haemosiderin, possibly a consequence of localized iron overload. Microliths contained mucosubstances. Macrophages often contained lipofuscin. No nerves were found in relation to the tumours.. The results suggest that, contrary to popular belief, phenotypes in canalicular adenoma do not reflect histogenetic concepts but rather may derive from the interplay between an altered secretory product, consisting of glycosaminoglycan and an immature form of glycoprotein, the lack of neuro-effector relationships and the different microenvironments throughout the tumour.

Topics: Adenoma; Aged; Aged, 80 and over; Calcium; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nerve Fibers; Phenotype; Salivary Gland Neoplasms; Salivary Glands, Minor

Thirty-five chordomas and more than 100 other tumors that have to be considered in the differential diagnosis, were immunohistochemically analyzed using a panel of antibodies including those to subsets of keratins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immunoreactivities in chordoma were compared with those in renal cell carcinoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chordomas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20. The keratin K8 and K19 reactivity was retained in those chordomas showing solid sheets of epithelioid, spindle cells, or cartilaginous metaplasia, and in one of two cases showing overtly sarcomatous transformation. In comparison, keratins were never present in skeletal chondrosarcoma, although K8 and to a lesser extent K19 were seen in occasional cases of ESMC with chordoid features. HBME-1 reacted strongly with chordoma and skeletal chondrosarcoma but was almost never positive in renal or colorectal carcinoma. These carcinomas lacked K5-reactivity, in contrast to chordoma. Chordomas were also consistently positive for neuron-specific enolase and occasionally focally for synaptophysin, but never for chromogranin. In contrast, pituitary adenomas regularly expressed the full spectrum of neuroendocrine markers and differed from chordoma by having a narrower repertoire of keratins, often showing negative or focal keratin 8- or AE1/AE3 reactivity and being almost always K19-negative. These findings indicate that chordoma can be immunohistochemically separated from tumors that can resemble it. Immunohistochemistry is especially useful in the diagnosis of small biopsy specimens that offer limited material for morphological observation.

Topics: Adenocarcinoma, Mucinous; Adenoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Chondrosarcoma; Chordoma; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Pituitary Neoplasms

Twenty-five cases of thyroid adenomas with Hurthle cell changes, both pure and focal, were studied histologically and immunohistochemically with two objectives: first to elucidate the relationship between the normal uninvolved thyroid and the adenoma; and second, to evaluate the role of immunohistochemical studies in adenomas with Hurthle cell changes. Representative sections were stained with a panel of nine antibodies directed against thyroglobulin (TG), high molecular weight keratin (HMK), low molecular weight keratin (LMK), p53, bcl-2, epithelial membrane antigen (EMA), S100, carcinoembryonic antigen (CEA) and HMB45. In all cases, uniform strong positive staining (+3) with TG and bcl-2 was seen in the normal thyroid tissue while the adenoma stained moderately positive (+2). The reverse pattern was observed with LMK staining. Non-adenomatous thyroid cells were p53-negative, the majority of the Hurthle cells, however, were p53-positive and adenomas with an increased number of Hurthle cells had an increased percentage of p53 staining. The expression of EMA was variable. All thyroid cells both outside and within the adenoma were S100-, CEA-4 and HMB45-negative in all cases. The exact significance of p53 overexpression in the Hurthle cells needs further evaluation.

Topics: Adenoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Melanoma-Specific Antigens; Mucin-1; Neoplasm Proteins; Proto-Oncogene Proteins c-bcl-2; S100 Proteins; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; Tumor Suppressor Protein p53

Cytokeratin (CK) patterns and albumin messenger RNA (mRNA) are investigated in 24 patients with benign hepatic lesions (7 patients with focal nodular hyperplasia [FNH], 10 with hepatocellular adenomas [HA], 1 with biliary hamartoma, 4 with biliary cysts, 2 with cystadenomas) and in 8 patients with cystadenocarcinoma, a rare liver malignancy. The lesions and surrounding tissue of the hepatocytic components expressed CK 8 and 18 at immunohistochemistry, whereas the biliary elements evidenced CK 8 and 18 and CK 7 and 19. The albumin mRNA, as detected by in situ hybridization (ISH), revealed different distributions in the hepatocytes of FNH and HA. In the benign biliary lesions, the normal hepatocytes surrounding the tumors expressed albumin mRNA, whereas the biliary structures did not. Interestingly, in the cystadenocarcinomas, albumin mRNA was observed not only in the hepatocytes of residual parenchyma, but also in neoplastic bile duct cells lining the carcinomatous cysts; no signal was identified in the nonneoplastic biliary elements. This indicates that cystadenocarcinomas have a mixed biological phenotype and suggests they could arise either from pluripotent cells or from neoplastic cells that reacquire epigenetic features. Our results suggest two possible diagnostic applications for albumin ISH: on routine sections, it could represent an important tool for distinguishing between cystadenoma and cystadenocarcinoma; and on fine needle biopsy specimens, it could reduce uncertainty between FNH and HA.

Topics: Adenoma; Adolescent; Adult; Aged; Albumins; Biliary Tract Neoplasms; Biomarkers, Tumor; Cell Differentiation; Cystadenocarcinoma; Cystadenoma; Cysts; Diagnosis, Differential; Female; Gene Expression; Hamartoma; Humans; Hyperplasia; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Liver; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Neoplasm Proteins; Phenotype; Protein Isoforms; RNA Probes; RNA, Complementary; RNA, Messenger; RNA, Neoplasm; Stem Cells

Metanephric adenoma is a recently described benign renal neoplasm with distinctive histologic features. The cytologic appearance and fluorescence in situ hybridization (FISH) studies of this tumor have not been described. We present a case from a 48-yr-old woman. Cytologically, the cells were arranged in tight, short papillae and loose sheets. The cells had scant cytoplasma, round monotonous nuclei with fine even chromatin and rare small nucleoli. Immunohistochemistry revealed no reactivity for epithelial membrane antigen (EMA), keratins (AE1/AE3, callus, 34BE12), or carcinoembryonic antigen (CEA). FISH showed a disomic pattern for chromosomes 7, 17, and for the chromosome 3 short arm. The differential diagnosis includes Wilms' tumor, renal adenoma, papillary renal cell carcinoma, and metastatic tumors. Both immunohistochemistry and FISH may be of help in distinguishing some of these lesions.

Topics: Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Neoplasm Metastasis; Tomography, X-Ray Computed; Wilms Tumor

We report an example of lipoadenoma of the parotid gland, a previously undescribed tumor of the salivary gland. It is a well-circumscribed tumor comprising an intimate admixture of mature fat cells and branching narrow tubules. The tubules were elongated and had small or absent lumina, resulting in a remarkable Sertoliform pattern. They were lined by columnar cells, which were supported by a basal cell layer. The latter cells lacked evidence of myoepithelial differentiation but were best highlighted by immunostaining for high molecular-weight cytokeratin (34 beta E12). Comparison with the normal salivary gland components showed the greatest homology of the neoplastic tubules with the striated duct, which normally has an incomplete basal cell layer. The latter phenomenon is under-recognized, with some current textbooks still describing the presence of a single cell type only in the striated duct of the salivary gland.

Topics: Adenoma; Adult; Humans; Immunohistochemistry; Keratins; Male; Parotid Neoplasms

We carried out an immunohistochemical analysis of nine spiradenomas and seven cylindromas. Our findings underscore the histomorphological similarities of the two adnexal neoplasms-namely, the expression of S-100 protein ascribed to eccrine differentiation within the tubular and large, pale-staining cells of both entities. Human milk fat globulin (HMFG) and lysozyme, two markers associated with apocrine differentiation, are expressed by tubular cells in spiradenomas and cylindromas. Lysozyme is also expressed in cylindromas by large, pale-staining cells. In addition, antibodies to alpha-smooth muscle actin strongly characterized the small basaloid cells of both types of neoplasm. Both spiradenomas and cylindromas expressed identical cytokeratin patterns. As with the various regions of eccrine and apocrine units, the expression by spiradenomas and cylindromas of keratins 7, 8, and 18 indicates differentiation toward the secretory tissue, whereas the expression of keratin 14 in some of the neoplastic cells points toward ductal differentiation. Malformed ductal and glandular structures in continuity with evolving spiradenomas and cylindromas in two of our cases also suggest that these tumors might arise from abortive adenxal anlagen.

Topics: Actins; Adenoma; Adenoma, Sweat Gland; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carrier Proteins; Cell Differentiation; Cell Lineage; Eccrine Glands; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Transport Proteins; Morphogenesis; Mucin-1; Muramidase; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Sweat Gland Neoplasms; Vimentin

Congenital epithelial tumours of the salivary glands are very rare. The Salivary Gland Registry maintained in the Department of Pathology. University of Hamburg, contains only three cases among a total of 6,646 salivary gland tumours from the years 1965-1994. The three cases were classified as congenital basal cell adenoma, two of the parotid gland and one of the submandibular gland. Histologically, the three adenomas were similar in structure to the adult counterpart of basal cell adenoma with solid, trabecular or tubular (duct-like) patterns. In some cystic spaces of the duct-like structures PAS- and Astra blue-positive substances were secreted. On immunocytochemistry, the luminal duct-like cells showed membranous expression of cytokeratins 3, 5, 6, 7, 13 and 19. In the isomorphic basaloid cells of the solid and trabecular cell nests few cells expressed cytokeratin. On the outside of the solid cell nests there were smaller elongated myoepithelial-like cells, which expressed cytokeratin 14 and vimentin. Cytokeratins 1, 2, 4 and 18 were not expressed. The pattern of expression reflects the different stages of maturity of the tumour cells and is related to the development of the salivary glands until the end of the 3rd embryonal month with an arrest of further cell differentiation. No acinic cells, invasive growth, recurrence or metastases were observed. The differential diagnosis includes other congenital salivary gland tumours, such as hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma or embryoma, carcinoma, hamartoma and teratoma.

Topics: Adenoma; Carcinoma; Diagnosis, Differential; Female; Hamartoma; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Microscopy, Electron; Parotid Neoplasms; Periodic Acid-Schiff Reaction; Submandibular Gland Neoplasms; Teratoma; Vimentin

The pathobiology of salivary neoplasms can best be studied in a model system that reflects the native state of the tumor. The present study describes the use of a three-dimensional collagen gel (organoid) system in which pleomorphic adenomas of the parotid gland were propagated in vitro. Five pleomorphic adenoma cultures were established as organoid gels and compared with touch-preparations or cryopreserved specimens of native tumor. The organoid cultures demonstrated normal DNA content, the expression of myoepithelial cell proteins, and the production of sulfated acid mucins; these cellular and secretory features mimicked those found in the archival specimens. Further, organoid cultures of pleomorphic adenoma could be initiated after monolayer culture, demonstrating that culture on a plastic support does not alter the nature of the cells. Development of an in vitro culture system that maintains the native state of pleomorphic adenoma is an important tool for studying the pathobiology of these tumors.

Topics: Actins; Adenoma; Adult; Aged; Biomarkers, Tumor; Chondroitin Sulfates; DNA, Neoplasm; Glycosaminoglycans; Humans; Immunohistochemistry; Keratins; Middle Aged; Organoids; Parotid Neoplasms; Tumor Cells, Cultured

Among the members of the carcinoembryonic antigen (CEA) family, CD66a (human C-CAM) and CGM2 (CEA gene family member 2) mRNAs are frequently down-regulated in colorectal cancer. In contrast, nonspecific cross-reactive antigen (NCA) mRNA is overexpressed in the majority of these carcinomas. In animal models, the rodent homologues of CD66a have been shown to act as tumor suppressors, suggesting an important role in carcinogenesis. Here we investigate the mRNAs of CD66a, CGM2, and NCA in 22 human colorectal adenomas and the respective normal mucosa specimens by Northern blots. The expression of both CD66a and CGM2 changed in a concomitant fashion. Using oligonucleotides specific for the N-terminal domains, two CD66a transcripts 3.9 and 1.5 kb in size were identified. These showed a greater than 50% down-regulation in 20 of 22 and 18 of 22 adenomas, respectively. Reduction of the CGM2 message was observed in 21 of 22 cases. Complete or near-complete losses of the CD66a 3.9-kb mRNA and the CGM2 message were found in 13 of 22 and 15 of 22 of the tumors, respectively. The medians of CD66a and CGM2 expressions were between 0.3 and 0.0, respectively. The tumor:normal ratio of NCA mRNA expression was increased up to 2.4-fold in 11 of 22 adenomas. Altogether, these results compare well to the changes reported previously for colorectal carcinomas. The high frequency and early appearance of dysregulation of members of the carcinoembryonic antigen family during colorectal tumorigenesis suggests that these changes may be important for the development of the malignant phenotype.

Topics: Adenoma; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation; Antigens, Neoplasm; Blotting, Northern; Carcinoembryonic Antigen; Cell Adhesion Molecules; Colorectal Neoplasms; Female; GPI-Linked Proteins; Humans; Intestinal Mucosa; Keratins; Male; Membrane Glycoproteins; Middle Aged; RNA, Messenger

To evaluate the cytokeratin pattern of expression of hyalinizing trabecular adenomas and to verify whether or not these tumours, that share morphological features with papillary carcinomas, present the stratified epithelial-type cytokeratins commonly found in ordinary papillary carcinomas.. This study consisted of the immunohistochemical detection of simple and stratified epithelial type cytokeratin filaments in a series of six hyalinizing trabecular adenomas, three papillary carcinomas with a trabecular growth pattern and two carcinomas combining hyalinizing trabecular and papillary patterns. Simple epithelial-type cytokeratins 7, 8, 18 and 19 were found in every case. Expression of the stratified epithelial-type cytokeratins 1, 5/6 and/or 13 was detected in four hyalinizing trabecular adenomas.. Based on this, as well as on the cytological features and on the frequent co-occurrence of hyalinizing trabecular adenoma and papillary carcinoma, we suggest that the former lesion may be considered a peculiar encapsulated variant of papillary carcinoma.

Topics: Adenoma; Adult; Aged; Carcinoma, Papillary; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Neoplasms

Topics: Adenoma; Adult; Cell Nucleus; Epithelial Cells; Female; Follow-Up Studies; Humans; Keratins; Oral Ulcer; Palatal Neoplasms

Previous studies indicate that keratins 7, 8 and 18 are present in all thyroid papillary and follicular lesions, but the distribution of other keratins has been incompletely characterized. The profile of individual keratin (K) polypeptides was evaluated immunohistochemically in over 200 non-neoplastic and neoplastic thyroid papillary and follicular lesions. Monoclonal antibodies to K19, K17, K16, K5/6 and K10 were applied in paraffin sections of formaldehyde-fixed tissue. K19 was present variably, often only focally in goitres, and was present only sporadically in papillary hyperplasia. However, K19 was strongly and uniformly expressed in virtually all papillary carcinomas, indicating differential diagnostic usefulness in differentiating papillary hyperplasia and papillary carcinoma. About half of the follicular carcinomas (defined as tumours strictly excluding the follicular variant of papillary carcinoma) were also strongly K19-positive, suggesting that K19 patterns are not reliable in differentiating papillary and follicular carcinoma. K17 and K5/6 were present in cysts and squamous metaplasia of goitres, and focally in papillary but only exceptionally in follicular carcinoma in areas of squamous differentiation and tumour cells in desmoplastic stroma. K16 in turn was present only focally in well-developed squamous metaplasia in goitres but was not found in differentiated thyroid carcinomas. K10, a high-molecular-weight keratin typical of epidermal differentiation, was identified neither in non-neoplastic nor in neoplastic differentiated thyroid lesions, including squamous metaplasia. These results indicate that papillary carcinomas differ from other differentiated thyroid tumours in their varying, usually focal, expression of stratified epithelial keratins that are partly but not exclusively related to squamous differentiation in such lesions. However, papillary carcinomas do not express truly epidermally restricted keratins; their previously described reactivity with polyclonal "epidermal keratin" antibodies most probably results from the reactivity of such antibodies with K19.

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

Twenty-four salivary gland tumours (six pleomorphic adenomas, two myoepitheliomas, five basal cell adenomas, six adenoid cystic carcinomas and five polymorphous low grade adenocarcinomas) were investigated by an immunocytochemical technique using monoclonal antibodies against cytokeratins (CKs) 7, 8, 10, 13, 14, 18 and 19. The luminal cells of ductal structures of the tumours reacted with all the CKs studied except for CK 13 and CK 10 and sometimes CK 14, showing an immunoprofile comparable to that of the intercalated segment of a normal salivary gland. The outer cells of the ducts rarely stained with CK 14, confirming that full differentiation of the myoepithelial cells is seldom achieved in tumours. Considerations were made regarding the intriguing expression of CK 14, the heterogeneous expression of CKs in the modified myoepithelial cells and the immunoprofile of the polymorphous low-grade adenocarcinoma.

Topics: Adenocarcinoma; Adenoma; Adenoma, Pleomorphic; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Keratins; Myoepithelioma; Neoplasm Proteins; Salivary Gland Neoplasms

Benign cutaneous adnexal tumors displaying divergent differentiation are rare, with very few well-documented cases reported in the literature. We describe eight cases of benign adnexal tumors showing a variable combination of eccrine, apocrine, and folliculosebaceous differentiation. Clinically, all tumors presented as solitary, slowly enlarging dermal or subcutaneous nodules located in the head and neck and the extremities. Histologically, they were characterized by well-circumscribed, unencapsulated nodules composed of a lobular proliferation of epithelial cells displaying a spectrum of trichogenic, sebaceous, apocrine, and eccrine differentiation. The histological spectrum included lobules and trabeculae of basaloid cells with glandular and ductal elements, well-formed folliculosebaceous units, primitive follicles, and foci of tricholemmal keratinization. Immunohistochemical evaluation in four cases showed similar cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen staining profiles as those reported for sweat gland adenomas; in addition, focal S-100 protein positivity and GCDFP-15 positivity could also be demonstrated, suggesting eccrine-apocrine differentiation. The tumors were most frequently confused histologically with other adnexal neoplasms, including sebaceoma, sebaceous adenoma, basal cell carcinoma, chondroid syringoma, and trichoepithelioma. The present series highlights the capability.

Topics: Adenoma; Adenoma, Pleomorphic; Adenoma, Sweat Gland; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carrier Proteins; Eccrine Glands; Epithelium; Female; Glycoproteins; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Basal Cell; S100 Proteins; Sebaceous Gland Neoplasms; Sweat Gland Neoplasms

In this study, we demonstrated the clonal origin of trisomy for chromosome 7 in epithelial cells of colon neoplasia. By using the double-target fluorescence in situ hybridization (FISH) technique in frozen tissue sections that were also immunostained for keratin and vimentin, ratio analysis of FISH signals for chromosomes 7 and 17 could be performed in epithelial (cytokeratin-positive) or stromal (vimentin-positive) areas. The data demonstrated that trisomy for chromosome 7 is found exclusively in the epithelial compartments and not in the stroma of colon adenocarcinoma. We then demonstrated the occurrence of trisomy for chromosome 7 in the different types of epithelial neoplastic cells, i.e., columnar and goblet cells, which were isolated from frozen tissue sections by mechanical disaggregation of colon tissue and mild lysis of the cells while protease activity was inhibited. In these cell suspensions, the columnar cells were detected with an antibody to villin, and the goblet cells were stained for mucin, whereas all cells were subsequently subjected to FISH for chromosome 7. For analysis of neuroendocrine cells, which are present in a very low frequency in colon neoplasia, frozen tissue sections that were immunostained for Chromogranin A could be used. Individual neuroendocrine cells could be distinguished in these thin frozen tissue sections. The presence of trisomy for chromosome 7 in all three different epithelial cell types strengthens our suggestion that this chromosomal aberration is found in the epithelial stem cell compartment of colon neoplasia.

Topics: Adenoma; Carcinoma; Cell Line; Chromosome Aberrations; Chromosomes, Human, Pair 7; Clone Cells; Colonic Neoplasms; Epithelium; Humans; In Situ Hybridization, Fluorescence; Keratins; Trisomy; Vimentin

Sialadenoma papilliferum (SP) is a rare, benign, salivary gland tumor which most commonly arises in the palate. It has a typical biphasic gross and microscopic appearance which distinguishes this tumor from other papillary-like tumors of the oral cavity. This study reports the clinico-pathologic features of 5 new cases and analyzes the morphologic and immunophenotypic features of their cell components. Adluminal epithelial cells of duct-like structures appeared immunoreactive to cytokeratin 19 and to S-100 protein antibodies; two subsets of basally-located cells were identified by means of immunohistochemistry. One cell subset expressed cytokeratin 14, S-100 protein, GFAP, vimentin and smooth muscle actin immunoreactivity; this antigenic profile is consistent with myoepithelial differentiation. The second subset of basal cells expressed cytokeratins 13 and 14 reactivity but it was negative to all other antibodies. Anti-CD 1a and anti-S-100 protein antibodies revealed distinct cells with dendritic processes which resembled Langerhans cells. The extralobular location of SP, the continuity between neoplastic duct-like structures and the surface epithelium along with the presence, within the excretory ducts adjacent to the tumour, of lesions which possibly precede the development of SP give further strength to the hypothesis of an origin from the excretory ducts of this tumor. Langerhans cells seem to be present in sialadenoma papilliferum but their role in this tumor is still unclear.

Topics: Actins; Adenoma; Adult; Antigens, Neoplasm; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Palate; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

A case of metanephric adenoma, a rare benign tumor of the kidney is reported, and the results of ultrastructural, immunohistochemical, and lectin histochemical studies are presented. The patient was a 47 year old Japanese man presenting with a left renal tumor by ultrasonography. The nephrectomy material revealed a well-demarcated tumor with medullary appearance, and on histological examination the tumor was composed of cuboidal cells forming regular small tubules with hyalinous stroma. Incomplete glomeruloid structures were formed in a few elongated tubules composed of columnar cells. Metanephric blastema was not observed in the tumor or in the normal kidney. By electron microscope, the tumor cells were observed to be immature cells with microvilli at the apical surfaces. The neoplastic tubules were surrounded by basal lamina. The tumor cells were immunoreactive for Leu 7, epithelial membrane antigen, vimentin, and low molecular weight cytokeratin, and were weakly immunoreactive for S-100 protein. Peanut agglutinin, soybean agglutinin, and Dolichos biflorus agglutinin were bound to the apical surfaces of the tumor cells.

Topics: Adenoma; Histocytochemistry; Humans; Intercellular Signaling Peptides and Proteins; Keratins; Kidney Neoplasms; Lectins; Male; Middle Aged; Peptides

Using 8 different monoclonal antibodies, immunohistology was performed on 36 follicular adenomas and on 28 follicular, 34 papillary, 27 medullary and 29 anaplastic carcinomas of the thyroid. The panel of antibodies was directed against broad-spectrum cytokeratins (pan-CK, antibody lu-5), against basic and acid high-molecular-weight CK of types #1, 5, 10 and 14, against basic (#5 and 6) and acid high-molecular-weight CK (#13) and against basic (#7 and #8) and acid low-molecular-weight CK (#19 and #20). With the exception of a large number of anaplastic carcinomas, nearly all other tumours exhibited strong immunoreactivity with antibodies against pan-CK, CK 8 and CK 19. CK 20 expression was exclusively shown for 2 medullary carcinomas. Reactivity for high-molecular-weight CK could only, each time focally, be demonstrated for 14 papillary and 2 follicular carcinomas and for 2 anaplastic carcinomas with partial squamous differentiation. Thirteen anaplastic carcinomas were not decorated by any of the CK antibodies applied. CK 7 staining exceeding the staining of individual cells was observed in 26 papillary cancers. In contrast, such a finding could only be obtained with each one follicular adenoma, medullary carcinoma and anaplastic carcinoma and with 5 follicular carcinomas. These results confirm earlier studies in that CK 20 expression among thyroid tumours is restricted to the neuroendocrine medullary carcinomas and that in a larger percentage of anaplastic thyroid carcinomas an epithelial phenotype can not be demonstrated even upon using broad-spectrum CK antibodies. New is the finding that there exist considerable differences between papillary carcinomas and all other non-papillary thyroid tumours regarding CK 7 expression. This result might be of differential diagnostic value for the distinction of follicular and papillary thyroid neoplasias which sometimes have an overlapping histological pattern.

Topics: Adenocarcinoma, Follicular; Adenoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Diagnosis, Differential; Humans; Keratins; Thyroid Gland; Thyroid Neoplasms

Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors arise from the proximal tubules. In the present study, lectin-binding characteristics and cytokeratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from which tumors arise. Lectin-binding histochemistry has been used as a marker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-molecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubules by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Ricinus communis (RCA-1), and Triticum vulgare and to the distal tubules by Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin binding and cytokeratin staining patterns of rat hereditary renal cell carcinoma, adenoma and the preneoplastic lesions of atypical tubules and hyperplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principally the proximal tubule.

Topics: Adenoma; Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Concanavalin A; Histocytochemistry; Hyperplasia; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lectins; Male; Plant Lectins; Precancerous Conditions; Rats; Rodent Diseases; Wheat Germ Agglutinins

The clinical and pathological features of three adnexal tumours of probable Wolffian origin are reported. One case was an incidental finding in a patient who died from ovarian carcinoma; in the other two cases the patients presented with lower abdominal pain. The three tumours were well-circumscribed, solid masses arising in the leaves of the broad ligament and histological examination showed bland epithelial cells forming tubular, solid and microcystic patterns. The immunohistochemical profile of the tumours was similar to that of Wolffian duct remnants. They co-expressed cytokeratin and vimentin and lacked epithelial membrane antigen (EMA) reactivity, in contrast to tumours of Müllerian origin which usually express EMA. The differential diagnosis of female adnexal tumours is discussed.

Topics: Adenoma; Adult; Female; Genital Neoplasms, Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Vimentin; Wolffian Ducts

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that has distinctive gross, histologic, and cytogenetic features, but for which only limited immunohistochemistry data have been reported. We compared 36 papillary RCCs and five renal cell adenomas with 19 non-papillary (clear cell and granular) RCCs using a variety of antibodies to keratin and carcinoembryonic antigen (CEA). Papillary tumors were often multifocal and associated with coexistent adenomas, whereas nonpapillary tumors generally lacked these features. Low-grade papillary RCCs demonstrated three occasionally overlapping histologic patterns (typical, trabecular, and sclerotic), whereas high-grade tumors were characterized by an admixture of many patterns. Immunohistochemically, 100% (36 of 36 cases) of the papillary tumors were positive for AE1/AE3, and 92% (33 of 36 cases) were positive for callus keratins; only 3% (one of 36 cases) stained for 34BE12, and 11% (four of 36 cases) weakly stained for CEA. The five renal cell adenomas were likewise positive for AE1/AE3 (five of five cases) and callus (five of five cases) keratins. In contrast, 85% (16 of 19 cases) of the nonpapillary tumors stained for AE1/AE3, but only 5% (one of 19 cases) stained for callus; none (0/19) stained for 34BE12, and 10% (2/19) weakly stained for CEA. The consistent expression of callus keratins by papillary RCCs and renal cell adenomas underscores the close relation of these lesions, providing additional evidence for their oncological distinction from nonpapillary RCCs.

Topics: Adenoma; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged

It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified.. Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and liver tumors of mice were verified by SDS-PAGE and Western blot analysis.. Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition, hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200 kDa) labeled with DBA as detected in bile.. Our results suggest that some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have the potential of biliary differentiation. DBA is a sensitive marker for malignant hepatocytes in mice.

Topics: Adenoma; Animals; Bile Ducts; Carcinogenicity Tests; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Immunohistochemistry; Keratins; Lectins; Liver Neoplasms; Male; Mice; Mice, Inbred Strains; Molecular Probes; Peanut Agglutinin; Plant Lectins; Precancerous Conditions; Retrospective Studies

Borderline nodule (BN) in the cirrhotic liver is considered to be a precancerous lesion leading to hepatocellular carcinoma (HCC). We investigated the distribution of cytokeratin 19 (CK 19)-positive biliary cells, recognizable by a monoclonal antibody AE1, in normal livers, chronic active hepatitis, cirrhosis, BN, and small HCC. The CK 19-positive biliary cells in the hepatic parenchyma were clearly divisible into two types (I and II). Type I cells were located within the hepatic parenchyma as small clusters forming small tubules (intraparenchymal ductules). Type II cells were bile ductules located in the peripheral rim of the hepatic lobules or hepatocellular lesions (peripheral ductular reaction) and were continuous with proliferated bile ductules in fibrous septae or portal tracts. In chronic active hepatitis and regenerative nodules of cirrhosis, a few type I cells and a variable number of type II cells were present. In the BN, all cases harbored a few type I cells as well as a variable number of type II cells. The type II cells in the BN were fewer in number and more randomly distributed than those in chronic active hepatitis and cirrhosis. Malignant foci in some BNs lacked CK 19-positive biliary cells. In small HCC, no CK 19-positive biliary cells were found; instead, AE1-positive HCC cells were present in three cases (17%). Although a great majority of type I cells corresponded to intraparenchymal ductules, some type I cells in the BN were composed of rather large tubules considered as interlobular bile ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Hyperplasia; Keratins; Liver; Liver Cirrhosis; Liver Neoplasms; Precancerous Conditions

Thirteen dermal cylindromas (DC) have been studied immunohistochemically using a panel of antibodies that stain different portions of normal eccrine and apocrine glands. Distinct staining patterns were found in the different cell populations of the tumor. Although the expression of cytokeratins (CK) 19 and 1/10/11 in occasional duct structures could indicate excretory (ductal) differentiation, a link between DC and apocrine secretory coil is suggested by the expression of alpha-1-antichymotrypsin, lysozyme, human milk factor globulin 1, alpha smooth muscle actin (1A4), and CK 8 and 18. The presence of intermingled S-100 protein-, HLA DR-, and CD1a-positive cells argues for the existence of Langerhans cells within the neoplasm. DC shares epithelial membrane antigen, carcinoembryonic antigen, mucin-like carcinoma-associated antigen (B12), laminin, collagen IV, fibronectin, and CD34(QBEND/10) expression with both eccrine and apocrine glands.

Topics: Actins; Adenoma; alpha 1-Antichymotrypsin; Antigens, CD1; Antigens, CD34; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Apocrine Glands; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Differentiation; Collagen; Coloring Agents; Eccrine Glands; Fibronectins; Gene Expression Regulation, Neoplastic; HLA-DR Antigens; Humans; Keratins; Laminin; Langerhans Cells; Mucin-1; Mucins; Muramidase; Neoplasm Proteins; S100 Proteins; Sweat Gland Neoplasms

A case of papillary tubular adenoma is reported. On microscopic examination the lesion, located on the scalp, showed a tubular-branching pattern, opening on the skin surface, and features of decapitation secretion. Immunohistochemical evidence of both eccrine and apocrine differentiation was found. This case, which on a clinicopathological basis alone could be classified as tubular apocrine adenoma, illustrates the difficulties in contrasting the latter to its eccrine counterpart (papillary eccrine adenoma) and suggests that the terms papillary tubular adenoma or tubulopapillary hidradenoma more accurately describe these lesions.

Topics: Adenoma; Adenoma, Sweat Gland; Adenoma, Villous; Adult; Antigens, Neoplasm; Apocrine Glands; Carcinoembryonic Antigen; Cell Differentiation; Diagnosis, Differential; Eccrine Glands; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Mucin-1; Neoplasm Proteins; Scalp; Skin Neoplasms; Sweat Gland Neoplasms

Applying immunohistochemical procedures for the detection of eight different cytokeratin (CK) polypeptides and other differentiation markers, we compared the staining patterns of normal cutaneous structures with those of benign adnexal tumors (n = 65). Syringomas exhibited a marker pattern highly reminiscent of that seen in normal dermal eccrine ducts (EMA in peripheral cells, CK 10 in intermediate cells, and CK 6, CK 19, and CEA in luminal cells). Nodular hidradenomas exhibited complex patterns suggesting relationship between tumor cells, including clear cells, and normal secretory coil cells (CK 7, CK 8, CK 19, and EMA); however, dermal-duct and epidermoid differentiation were also detectable. In both cylindromas and spiradenomas, zonal staining patterns were apparent: modified myoepithelial cells were positive for smooth-muscle-type actin, while the luminal cells mainly expressed ductal markers (CK 6 and CK 19) and, less prominently, secretory-coil markers including CK 7. Eccrine poromas exhibited a widespread reaction for CK 5/6 and EMA, analogous to peripheral dermal duct cells, but focal maturation toward inner-ductal and secretory-coil cells was also demonstrable. The staining pattern observed in trichoepitheliomas resembled that of the outer but not the inner root sheath. In conclusion, the detailed marker profiles obtained in the present study have broadened our understanding of the differentiation and nature of these highly singular tumor types.

Topics: Adenoma; Adenoma, Sweat Gland; Antibodies, Monoclonal; Binding, Competitive; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Cell Differentiation; Epidermal Cells; Epidermis; Humans; Immunohistochemistry; Keratins; Neoplasms, Basal Cell; Reference Values; Skin Neoplasms; Sweat Glands; Syringoma

Ten cases of so-called "tubular" adenoma and six cases of fibroadenoma of the breast have been investigated with an immunohistochemical technique with the aim of providing both more details on their immunophenotype and of ascertaining the possible relationships between tubular adenoma and fibroadenoma. Smooth Muscle Actin, Cytokeratin 14, GFAP, S-100 Protein and Vimentin immunoreactivity have clearly demonstrated that cells with myoepithelial immunophenotype are one of the major cell components in breast adenomas. Epithelial Membrane Antigen (EMA), Human Milk Fat Globule II (HMFG II), Estrogen and Progesterone receptors have been detected in adluminal epithelial cells exclusively. Furthermore, Smooth Muscle Actin and Vimentin highlighted an abundant myofibroblastic component, intermingled with tubular structures in both tumor types. A low percentage (10-22%) of adluminal cells and of myofibroblasts showed Ki-67 immunoreactivity in tubular adenomas and in fibroadenomas, whereas only rare myoepithelial cells demonstrated Ki-67 positivity in both tumor types. These data seem to indicate that several cell components of both epithelial and mesenchymal origin (epithelial cells, myoepithelial cells, myofibroblasts) are involved in the genesis of tubular adenomas. The morphological and immunohistochemical features of tubular adenomas closely resemble, in some areas of the tumors, those of fibroadenoma. Therefore, they may represent histogenetically related neoplasms with exuberant ductular component in tubular adenomas and predominant stromal component in fibroadenoma.

Topics: Actins; Adenoma; Adolescent; Adult; Breast Neoplasms; Female; Fibroadenoma; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Middle Aged; Mucin-1; Muscle, Smooth; Receptors, Estrogen; Receptors, Progesterone; S100 Proteins; Vimentin

A histologic and immunohistochemical study was performed to identify the histogenesis of solid cell nests (SCN), which were found incidentally in 11 thyroid glands obtained by surgery. Histologically, SCN consisted of small nests showing solid and cystic structures. Cystic features of SCN were found in 3 of the 11 cases (27%), with mucinous materials in their lumens. Some goblet cells were also present in three cases (27%). In one case, SCN were associated with lymphocyte aggregation. Immunohistochemical analysis using serial sections of the SCN showed that the cells comprising SCN were positive for calcitonin in 5 cases (45%), for carcinoembryonic antigen (CEA) detected using polyclonal antibody in 11 (100%), for CEA detected using monoclonal antibody in 3 (27%), for calcitonin gene related peptide in 2 (18%), for chromogranin A in 5 (45%), and for keratin in 11 (100%). These antigens were expressed concomitantly in the same SCN, but the number and distribution of the positive cells for the antigens were different for each antigen in the same SCN in each case. These findings strongly support the view that SCN are derived from the ultimobranchial body. In addition, the biologic function to produce the antigens may vary greatly in individual cells comprising SCN.

Topics: Adenoma; Adult; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoembryonic Antigen; Carcinoid Tumor; Carcinoma, Papillary; Chromogranin A; Chromogranins; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Thyroglobulin; Thyroid Neoplasms

The pathologic diagnosis of thyroid tumors is often difficult and subjective. Immunohistochemical markers including high molecular weight cytokeratin (HMW-CK), cytokeratin-19 (CK-19) and epithelial membrane antigen have been suggested to be helpful in the distinction of various types of thyroid neoplasia. We collected frozen and/or paraffin-embedded tissues from a total of 116 surgically resected thyroids including 31 nodular hyperplasias, 18 follicular adenomas, 48 papillary carcinomas and 19 follicular carcinomas, stained them for HMW-CK, CK-19 and epithelial membrane antigen, and graded the results on a scale from 0 to 3+. Although little staining for HMW-CK was seen in paraffin-embedded tissues, different results were obtained when both HMW-CK and CK-19 were tested on frozen tissues. In papillary carcinomas, including the follicular variant of papillary carcinoma, diffuse positivity for these antigens was seen immunohistochemically, and these antigens significantly distinguished papillary carcinomas from follicular neoplasms and nodular hyperplasias. Focal staining for epithelial membrane antigen was found in all pathological processes; thus this marker was not useful. We conclude that HMW-CK and CK-19 are useful in the distinction of papillary carcinomas from follicular adenomas, follicular carcinomas, and nodular hyperplasias when applied to frozen tissues. We recommend that samples of thyroid follicular nodules be frozen, and retrieved if necessary to aid in the differential diagnosis of these tumors.

Topics: Adenocarcinoma, Follicular; Adenoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Papillary; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Molecular Weight; Mucin-1; Thyroid Neoplasms

Topics: Adenoma; B-Lymphocytes; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Lip Neoplasms; Male; Middle Aged; Skin Neoplasms; T-Lymphocytes

Duct ectasias (n = 2) and different types of benign canine mammary tumours (n = 19) were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types (K), alpha-smooth muscle actin, vimentin, and desmin. In the duct ectasias and in most tumours the epithelial structures revealed an inner and outer cell layer. The inner cell layer was characterized by labelling with K 7, 8, 18, 19 and mostly also with K 4 and/or K 10 MoAbs. The outer cell layer was almost invariably labelled by K 14, K 14 and 17, and a-smooth muscle actin MoAbs. The labelling patterns of both duct ectasias and tumours corresponded largely to the patterns observed in normal mammary gland tissue, although a more distinct heterogeneity was seen. Tumours histomorphologically assumed to be of a myoepithelial origin did not show immunohistochemical features of myoepithelial cells. The myoepithelial nature of the vast majority of spindle-shaped cells present in the adenomas of the complex type and in the fibroadenomas of the benign mixed type could not be confirmed immunohistochemically. These cells, however, unequivocally expressed vimentin, suggesting proliferation of stromal cells in these tumours, which in the fibroadenomas of the benign mixed type may show metaplasia to bone or cartilage. In the duct ectasias and in some tumours, a fraction of elongated stromal cells, probably representing myofibroblasts, was labelled with the alpha-smooth muscle actin MoAb.

Topics: Actins; Adenoma; Animals; Antibodies, Monoclonal; Desmin; Dilatation, Pathologic; Dog Diseases; Dogs; Female; Fibroadenoma; Immunoenzyme Techniques; Immunophenotyping; Intermediate Filament Proteins; Keratins; Male; Mammary Glands, Animal; Mammary Neoplasms, Animal; Mastitis; Papilloma, Intraductal; Vimentin

We compared clinical features, including endocrinological and radiological findings, histological features and the proliferative parameters (PCNA, MIB-1 and AgNORs) with immunohistochemical features in growth hormone (GH) secreting pituitary adenomas. 18 cases were divided into two groups based on immunohistochemical intracytoplasmic stainings for cytokeratin: a prominent dot-like pattern (group I, 6 cases) and a diffuse perinuclear pattern (group II, 12 cases). Patients in group I (6 females, m = 37.6 years old) were younger, showed female predominance and had a shorter history of acromegaly compared with patients in group II (7 males, 5 females, m = 44.9 years old). Although the size of the adenomas tend to be larger in group I, no difference was recognized in plasma GH levels between the two groups. Increased serum prolactin (PRL) levels were accompanied more common in group I. Abnormal GH responses to TRH and LHRH injection and GH suppressions to bromocriptine administration were more frequently noted in group II than group I. Surgical approaches were transcranial in most cases of group I and transphenoidal in group II. There was no difference in surgical results as to the correction rate of GH levels between the two groups. Histopathologically, group I adenomas were mostly chromophobic, weakly positive for GH, and were generally negative for PRL and alpha-subunit. On the other hand, group II adenomas were mostly acidophilic, diffusely stained for GH, and were often positive for PRL and alpha-subunit. However, there was no significant difference in proliferating parameters between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adenoma, Acidophil; Adenoma, Chromophobe; Adult; Aged; Female; Growth Hormone; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pituitary Neoplasms

Sebaceous carcinoma is an infrequent skin tumor and its histological features sometimes closely resemble those of squamous cell carcinoma (SCC) and basal cell epithelioma (BCE), which often leads to a misdiagnosis. In the present immunohistochemical study, however, sebaceous carcinoma exhibited quite a different expression of keratins from SCC and BCE. We immunohistochemically examined 26 excised specimens of sebaceous carcinoma, 10 of SCC and 12 of BCE of the eyelids, using two monoclonal antibodies against high molecular weight keratins, 34 beta B4 (68kd) and 34 beta E12 (56kd, 56.5kd, 58kd), and two monoclonal antibodies against low molecular weight keratins, 35 beta H11 (54kd) and CAM5.2 (39kd, 43kd, 50kd). The cases of sebaceous carcinoma were positive with 34 beta B4 (23%), 34 beta E12 (54%), 35 beta H11 (81%) and CAM5.2 (73%). Of the four anti-keratin antibodies used in this study, 35 beta H11 was negative in all cases of SCC or BCE. These findings indicate that when sebaceous carcinoma is suspected, but no fat staining appropriate materials are available, a monoclonal antibody against low molecular weight keratin, 35 beta H11 (54kd), can be a useful tool to immunohistochemically rule out both SCC and BCE.

Topics: Adenocarcinoma, Sebaceous; Adenoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Sebaceous Gland Neoplasms; Skin Neoplasms

Basal cell adenocarcinoma is a recently defined category of salivary gland neoplasms. As the terminology implies, this group of tumors has many histopathologic features that are similar to the more well-known basal cell adenomas. To better characterize these tumors, 23 basal cell adenocarcinomas were reviewed and compared with 11 basal cell adenomas with the use of light microscopic and immunohistochemical methods. Evaluation of cytokeratin, S-100 protein, glial fibrillary acidic protein, carcinoembryonic antigen, epithelial membrane antigen, smooth muscle actin, vimentin, B72.3, Ber-EP4, and milk fat globulin immunoreactivity was performed. Parallel to the morphologic similarity, the immunoprofiles of the basal cell adenocarcinoma and basal cell adenoma were quite similar. Both tumors showed reactivity patterns indicative of ductal epithelial and myoepithelial differentiation. In addition, reactivity to some polymorphic epithelial mucins was observed, which suggested glandular differentiation. The identification of antigens found normally in myoepithelial and epithelial cells supports the concept that these tumors are derived from pluripotential salivary gland epithelial cells. The comparable immunohistochemical profiles imply evolvement from similar cell lines and lead us to conclude that distinction between the two is not possible on the basis of these findings.

Topics: Actins; Adenocarcinoma; Adenoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Parotid Neoplasms; S100 Proteins; Submandibular Gland Neoplasms; Vimentin

The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors.

Topics: Adenoma; Antibodies, Monoclonal; Antigens, Differentiation; Biomarkers, Tumor; Cell Transformation, Neoplastic; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovary

Renal cell carcinoma can have solitary adrenal metastasis years or even decades after resection of the primary tumor. The difficulty in distinguishing an adrenocortical adenoma from a solitary metastasis of a renal cell carcinoma prompted us to study 10 adrenal adenomas, 11 primary renal cell carcinomas, and three renal cell carcinomas metastatic to the adrenal gland by immunohistochemical stains and flow cytometry to determine if these techniques could help make the distinction. Immunohistochemical staining was performed for detection of cytokeratin, vimentin, and epithelial membrane antigen (EMA). Cytokeratin, vimentin, and EMA were detected in 10/11, 9/11, and 11/11 primary renal cell carcinomas, respectively, and 1/3, 2/3, and 3/3 metastatic renal cell carcinomas, respectively. All cases of adrenal adenoma were negative for the three antigens. DNA content analysis by flow cytometry showed no evidence of an abnormal DNA stemline in any of the cases except one renal cell carcinoma. We conclude that staining for EMA is consistently strongly positive in primary and metastatic renal cell carcinomas and consistently negative in adrenal adenomas, proving to be a useful distinguishing marker. Cytokeratin and vimentin, although uniformly absent in adrenal adenomas, are variably and often only weakly positive in renal cell carcinomas, and therefore of less help in making the distinction. Flow cytometry analysis has no discriminatory value in these cases.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Membrane Glycoproteins; Mucin-1; Ploidies; Vimentin

Fifty-eight formalin-fixed paraffin-embedded canine mammary tumors, 19 malignant and 39 benign, were used in this study. Tumors were obtained from dogs submitted for surgical resection of lesions at private veterinary practices in Brussels or from the surgery unit of the Faculty of Veterinary Medicine, University of Liège. Immunohistochemical evaluation was performed, using monoclonal antibodies directed against keratins 8-18 and 19, vimentin, desmin, and alpha-actin and polyclonal antibodies directed against high-molecular-weight keratins and S-100 protein. The main cell types, epithelial, myoepithelial, and connective, were identified, and myoepithelial cells represented the major component of most tumors, both benign and malignant. Myoepithelial cells had five patterns: resting and proliferative suprabasal cells, spindle and star-shaped interstitial cells, and cartilage. Reactivity to keratin 19, vimentin, alpha-actin, and S-100 protein suggested a progressive transformation from resting cells to cartilage. Epithelial cell reactivities were limited to keratins; only keratinized cells were positive for polyclonal keratins. Myofibroblasts were positive for both vimentin and alpha-actin, and connective tissue cells were positive for vimentin. Myoepithelial cells appeared to be the major component of carcinomas, justifying reevaluation and simplification of histomorphologic classifications, with a "pleomorphic carcinoma" group including all carcinomas except squamous, mucinous, and comedo carcinomas. Immunohistochemical evaluation, in addition to routine hematoxylin and eosin histopathologic evaluation is recommended for precise classification of canine mammary tumors.

Topics: Actins; Adenoma; Animals; Carcinoma; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Vimentin

Human basal epithelium (myoepithelium)-specific (312C8-1) and luminal epithelium-specific (13H5) cytokeratin antibodies were applied to frozen sections of normal canine mammary tissues (seven), benign adenomas and hyperplasias (five), mixed tumors (12), and adenocarcinomas (18) to determine if epithelial subsets could be discriminated by the use of an avidin biotin peroxidase complex immunohistochemical procedure. The 312C8-1 and 13H5 antibodies were consistently reactive with basal and luminal epithelium, respectively, in the normal mammary gland (7/7) and in benign adenomas and hyperplasias (5/5). Mixed mammary tumors had similar basal and luminal epithelial reactivity and also had proliferating spindle-shaped stromal cells that were reactive with 312C8-1 (10/12) and 13H5 (4/12). The adenocarcinomas were subclassified into basal, luminal, and basal/luminal on the basis of 312C8-1 reactivity (4/18), 13H5 reactivity (2/18), and dual reactivity with mutually exclusive anatomic distribution (11/18), respectively. Those tumors with dual immunoreactivity were indicative of noninvasive carcinomas. Dogs with neoplasms that were reactive with 312C8-1 and nonreactive with 13H5 had local recurrence or distant metastasis within 2 weeks to 6 months after diagnosis. Other antibodies used for comparison were pan cytokeratin AE1/AE3, actin HHF35, and vimentin. 312C8-1 and 13H5 antibodies are specific for canine mammary basal and luminal epithelium, respectively, and by employing these antibodies, the origin and differentiation of canine mammary neoplasms can be determined more accurately than on the basis of hematoxylin and eosin-stained tissue alone.

Topics: Actins; Adenocarcinoma; Adenoma; Animals; Dog Diseases; Dogs; Female; Hyperplasia; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Vimentin

Fibroblast contamination of epithelial tumor cell cultures is of great concern when examining tumor cells in vitro for specific biochemical and cytogenetic changes. The observations of normal karyotypes in thyroid tumor cell cultures have raised the concern of whether residual tissue fibroblasts might obscure the cytogenetic analysis of transformed epithelial cells. We have characterized early passaged thyroid tumor cells to examine the proportions of epithelial and fibroblastic cell types. Cells were analyzed by immunocytology using antibodies recognizing the thyroid prohormone thyroglobulin, epithelial cytokeratins, and vimentin, a mesenchyme marker. Tumors consisted of one follicular adenoma and five papillary carcinomas. When examined by day 15 in culture, all cells contained filaments composed of vimentin, which most likely represents an adaptation to culture conditions. Double immunofluorescence staining for thyroglobulin and cytokeratin revealed the presence of not only epithelial but also spindle-like fibroblastoid cells possessing thyroid epithelial cell markers. The results suggest that in thyroid tumor cultures there is a unique cell type intermediate between epithelial and mesenchyme phenotypes that must be considered when performing cytogenetic analysis.

Topics: Adenoma; Artifacts; Biomarkers; Carcinoma, Papillary; Cell Differentiation; Culture Techniques; Epithelium; Fibroblasts; Genetic Markers; Humans; Keratins; Neoplasm Proteins; Thyroglobulin; Thyroid Neoplasms; Tumor Cells, Cultured; Vimentin

Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin. In NC, alpha 2 staining was strongest in crypt cells; alpha 1,3 and alpha v, and beta 1,3 and beta 4, and Ck 20 and villin predominated in superficial enterocytes. In TA and VA, monolayered glands showed integrin, Ck 20 and villin patterns that differed slightly from both crypt and superficial enterocytes. Complex glands in VA showed decreased integrin staining and basal polarization; Ck 20 and villin were strong only in luminal cells. CA showed overall weaker integrin staining than adenomas. Regardless of invasion depth, well formed malignant glands mimicked TA; pleomorphic glands mimicked VA with focal basal integrin polarization and solid clusters displayed scanty integrins, uneven Ck 20, and villin in occasional cells. Diverse integrins in crypt compared with superficial enterocytes reflect changing adhesive requirements as cells migrate and terminally differentiate. Decreasing expression and altered distribution of integrins, Ck 20 and villin noted in TA, VA, and in CA of increasing grade indicate that certain adhesive and cytoskeletal features more closely relate to glandular architecture than to depth of invasion.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Carcinoma; Carrier Proteins; Cell Differentiation; Colon; Colonic Neoplasms; Epithelium; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Integrins; Keratins; Microfilament Proteins; Tissue Distribution

In this study, we compared the clinical and endocrinological characteristics, neuroimaging findings, surgical outcome, and conventional histological findings (including immunohistochemistry) with the electron microscopic appearance of 31 growth hormone (GH)-producing adenomas. By electron microscopy, these 31 tumors were divided into 23 densely granulated somatotroph adenomas (DG adenomas) and 8 sparsely granulated somatotroph adenomas (SG adenomas). SG adenomas more frequently affected younger women, but no significant correlation was found between the adenoma type and the characteristic signs and symptoms of acromegaly, the incidence of diabetes mellitus or hypertension, or the basal serum GH and insulin-like growth factor I levels. A distinct response of GH to thyrotropin-releasing hormone, bromocriptine, or GH-releasing hormone was significantly more common in patients with DG adenomas than in those with SG adenomas, whereas the incidence of a response to gonadotropin-releasing hormone or oral glucose was not significantly different between the two groups. An analysis of neuroimaging findings and surgical results indicated that SG adenomas were more likely to be macroadenomas with suprasellar extension or invasive tumors and had a lower surgical cure rate. However, postoperative radiotherapy seemed to be similarly effective in both types of adenoma to prevent a tumor recurrence and to reduce postoperative GH basal level in serum. Light microscopy showed that DG adenomas were mainly acidophilic and were immunopositive not only for GH but also for prolactin (43%), the beta subunit of thyroid-stimulating hormone (26%), and the alpha subunit of glycoprotein hormone (87%), whereas SG adenomas were almost all chromophobic and only revealed immunopositivity for GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adenoma, Chromophobe; Adult; Biomarkers, Tumor; Bromocriptine; Cytoplasmic Granules; Diabetes Mellitus; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Hypertension; Keratins; Middle Aged; Neoplasm Proteins; Pituitary Neoplasms; Prolactin; Thyrotropin-Releasing Hormone; Treatment Outcome

Middle ear adenoma is a rare benign tumor that exhibits a pleomorphic histological pattern, with solid, cribriform, tubular and trabecular features, which often lead to a diagnosis of a malignant tumor. We report a case of middle ear adenoma, displaying the typical amphicrine biphasic cell growth, better visualized by immunohistochemical and ultrastructural studies. These tumors are composed of two cell types, endocrine B cells containing neurosecretory granules and labelled with anti-keratin, anti-vimentin and anti-neuron specific enolase antibodies, and exocrine A cells containing mucous granules and immunoreactive with anti-keratin and anti-epithelial membrane antigen antibodies. These immunohistochemical and/or ultrastructural characteristics may be helpful to confirm the diagnosis of middle ear adenoma which should be treated by local excision without additional therapy. The essential identity of middle ear adenoma and so called carcinoid tumors of the middle ear is highlighted. We propose to name these tumors middle ear amphicrine adenoma which better reflects their benign and biphasic nature.

Topics: Adenoma; Adult; Antibodies; Ear Neoplasms; Ear, Middle; Humans; Immunohistochemistry; Keratins; Male; Phosphopyruvate Hydratase; Vimentin

The distribution pattern of cytokeratin (CK) subtypes, an intermediate filament of cytoskeleton, was examined in adenomas and carcinomas of the colon and rectum. For the detection of the cytokeratin subtypes, monoclonal antibodies to the 54 Kd keratin polypeptide (CK No. 7 according to Moll's classification), 52.5 Kd (CK No. 8), 45 Kd (CK No. 18), and 40 Kd (CK No. 19) were used for immunohistochemical observation. Although No. 7 was positive in normal mucosa and adenoma with mild to moderate atypia, it could not be recognized in carcinoma. On the other hand the expression of No. 18 was confirmed in carcinoma, adenoma, and normal mucosa, and there were some differences in its distribution pattern in those with or without glandular formation and in areas showing infiltration of tumor cells. No. 18 expression was on the luminal side of normal colonic mucosa, adenoma, and well-differentiated adenocarcinoma; in the infiltrating area its reactivity was localized diffusely in the cytoplasm of tumor cells showing moderately or poorly differentiated adenocarcinoma cells. As to No. 8 and No. 19, they were recognized in normal mucosa, adenoma, and carcinoma. These results suggested the intimate relationship between expression of CK subtypes, cellular differentiation, and structural differentiation of colorectal carcinoma.

Topics: Adenocarcinoma; Adenoma; Colon; Colonic Neoplasms; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Keratins; Rectal Neoplasms; Rectum

An adrenocortical oncocytic neoplasm was detected incidentally in a 58-year-old man. The tumour weighted 315 g, showing haemorrhagic areas and broad fibrous bands. It was composed exclusively of large eosinophilic cells packed with mitochondria showing flat and infrequent tubulovesicular cristae and regression of steroid-related organelles. Occasional annulate lamellae and mitochondrial osmiophilic inclusions were present. Vimentin was diffusely expressed, whereas AE1/AE3 cytokeratin was detected in half of the cells; a focal punctate pattern of staining was exclusively observed for cytokeratin peptides 8 and 18. The patient had no evidence of disease 21 months after surgery.

Topics: Adenoma; Adrenal Cortex Neoplasms; Humans; Keratins; Male; Middle Aged; Mitochondria; Vimentin

Morphological analysis of the sclerotic changes in peripheral lung carcinoma (PLC) and nephrosclerosis in renal-cell carcinoma (RCC) established a promoting role of sclerosis in carcinoma development. The pneumosclerosis role as a background process in the PLC development is proved by the following facts: high proportion (83%) of the carcinoma in the scar among PLC; identity of the scar collagen composition in PLC and that in metatuberculosis and metapneumonic pneumosclerosis foci; detection of metatuberculosis foci in 75% of PLC; the presence of the precancerous changes in the epithelium entrapped in the pneumosclerotic foci, not only with signs of morphological atypia, but with the disturbance of nuclear DNA and cellular oncogene expression as well. The association of RCC with nephrosclerosis is shown by a high proportion (82.7%) of the RCC development against the background of nephrosclerosis; the dependence of the so-called cortical adenoma development on the degree of nephrosclerosis; epithelial proliferation in the nephrosclerotic foci with the appearance of undifferentiated cells with the altered DNA content and the expression of cytokeratins and vimentine. Carcinoma morphogenesis against the background of sclerosis may be described as follows: development of sclerosis (focal and/or diffuse), the appearance of the focal epithelial hyperplasia in the scar, dysplasia or adenoma and finally carcinoma.

Topics: Adenoma; Carcinoma, Renal Cell; Cell Differentiation; Cell Division; Collagen; DNA; Humans; Keratins; Kidney Neoplasms; Lung Neoplasms; Nephrosclerosis; Precancerous Conditions; Sclerosis; Vimentin

An unusual coexpression of glial fibrillary acid protein (GFAP), keratin and vimentin occurs in pleomorphic adenoma of salivary gland. We designed this study to see if coexpression of the markers was also present in monomorphic adenoma of the salivary gland and whether monomorphic adenoma could be distinguished from other salivary gland tumours by marker studies. Immunocytochemical markers were used on fine needle aspiration samples from four cases of monomorphic adenoma, two cases of oncocytic adenoma, three cases of adenoid cystic carcinoma and four cases of pleomorphic adenoma. While positivity for cytokeratin, vimentin and S-100 was consistently found in all cases of monomorphic adenoma, only cytokeratin was expressed in adenoid cystic carcinoma. In pleomorphic adenoma, GFAP, cytokeratin and vimentin were coexpressed while in cases of oncocytic adenoma none of the markers was localized. Thus, it appears that by using a combination of GFAP, cytokeratin, vimentin and S-100 a distinction between these neoplasms may be possible. However, a larger study is needed to establish the usefulness of this approach.

Topics: Adenoma; Adenoma, Pleomorphic; Biomarkers, Tumor; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Bile duct adenomas are small nodules that are usually found incidentally on the liver surface at abdominal surgery or autopsy. We recently analyzed two such lesions that, in addition to the typical small caliber ducts, contained periductular nests and clusters of uniform round cells, suggestive of endocrine cell proliferation. Follow-up of these patients did not show endocrine tumors elsewhere. The lesions were studied by immunohistochemistry (avidin-biotin-peroxidase technique) and compared with conventional bile duct adenomas (seven cases). The results showed these cells to decorate with several endocrine markers, namely, neuron-specific enolase, chromogranin, synaptophysin, and Leu-7. Endocrine markers were not seen in the cells of conventional bile duct adenomas. Epithelial markers, that is, cytokeratin (CAM 5.2 antibody) and epithelial membrane antigen, were expressed by the cells composing both conventional bile duct adenomas and those with endocrine-like cells, although with less intensity in the endocrine cell clusters. We suggest that some bile duct adenomas contain endocrine cell proliferations that morphologically may resemble a small carcinoid tumor or the so-called pulmonary tumorlet. Neurosecretory granules have previously been identified in some cholangiocarcinomas and in bile duct proliferation associated with cholestasis. The endocrine clusters in biliary adenomas may constitute a diagnostic pitfall and must be separated from metastases of carcinoids or islet cell tumors.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antigens, Differentiation; Bile Duct Neoplasms; Bile Ducts; Biopsy; Carcinoembryonic Antigen; CD57 Antigens; Chromogranins; Diagnosis, Differential; Endocrine Glands; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Phosphopyruvate Hydratase; Synaptophysin

Chemically induced mouse lung tumors exhibit distinctive growth patterns, characterized by an alveolar or solid appearance, a papillary appearance, or a combination of the two. Lung tumors induced in strain A/J mice by either benzo(a)pyrene (BP) or by N-nitrosoethylurea (ENU) were examined for expression of low- and high-molecular-weight cytokeratins. Simple cytokeratins (low molecular weight) were found in all epithelial cells of the normal mouse lung and in all tumor types, whereas higher-molecular-weight cytokeratins were found only in normal bronchiolar cells and in papillary tumor cells. These data lend support to the hypothesis that chemically induced papillary lung tumors in strain A/J mice are derived from bronchiolar Clara cells.

Topics: Adenoma; Animals; Benzopyrenes; Ethylnitrosourea; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mice; Mice, Inbred A; Microscopy, Electron

The distribution of cytokeratin (CK) polypeptides expressed in syringomas (12 cases) was compared with that in normal eccrine sweat ducts using immunohistochemical techniques on paraffin-embedded tissue. Intradermal and intraepidermal segments of the eccrine duct showed reactivity with an antibody to CK1/5/10/11 in all cell layers, whereas CK19 expression was restricted to the luminal cell layer. CK14 was expressed in all cells of the eccrine duct except for the peripheral cells of the intraepidermal duct. Expression of CK5/6 was seen in the basal cells of the dermal duct and of the lower intraepidermal duct (sweat duct ridge) exclusively. Reactivity with an antibody to CK1 was found in the intermediate cells of the uppermost part of the eccrine dermal duct. In addition, this antibody gave a strong staining of the peripheral cells of the intraepidermal duct, leaving basal cells of the sweat duct ridge and luminal cells unstained. In syringoma, CK distribution was essentially comparable with that found in the uppermost part of the dermal duct and in the sweat duct ridge. Namely, ductal luminal cells expressed CK1/5/10/11, CK19, and variably CK14. Intermediate cells of ductal structures and solid nests were homogeneously stained by antibodies to CK1 and CK1/5/10/11, whereas CK14 was expressed heterogeneously. The basal or outermost layer of ductal structures and solid nests was reactive with antibodies to CK1/5/10/11, CK5/6, and CK14. With regard to CK expression, the results indicate that syringoma represents a tumor differentiating toward both the uppermost part of the dermal duct and the lower intraepidermal duct (sweat duct ridge) of the eccrine sweat gland.

Topics: Adenoma; Cell Differentiation; Cell Transformation, Neoplastic; Eccrine Glands; Epidermis; Humans; Keratins; Peptides; Skin; Sweat Gland Neoplasms

During the last several decades, immunohistochemical studies of tumors, along with other approaches, have suggested that the clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic changes. However, CNS may provide a different microenvironment for activation and proliferation than other tissues. The tissue-specific distribution of intermediate filament proteins, in particular the keratins, permits their use as marker in histopathology, but several important exceptions are recognized. In this connection, it is of interest that, according to the other reports, glial tumors may be positive for different anti-keratin antibodies. However, the gliomas did not show an immunoreaction in any of the cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumors have particularly re-emphasized the need for new thinking about patterns of classification. The diagnosis of malignant melanoma has been considerably facilitated recently by the introduction of immunohistological labelling with antibodies selective against melanoma antigen (HMB-45). Our results confirmed the necessity of cautious interpretation of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several non-melanotic tumors.

Topics: Adenoma; Antibody Specificity; Biomarkers, Tumor; Central Nervous System Neoplasms; Humans; Immunohistochemistry; Keratins; Neoplasm Metastasis; Neoplasms; Pituitary Neoplasms

The paper describes the value of immunohistologically estimated differences in the intermediate filament protein composition of the different cell types of human adenohypophysis and the corresponding pituitary adenomas. Interestingly, some tumors failed to express any type of intermediate filament proteins, whereas other coexpress cytokeratins and vimentin/or neurofilament protein.

Topics: Adenoma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Pituitary Gland; Pituitary Neoplasms; Vimentin

The cytoskeleton forms a complex structural network which is of major importance for both structural integrity and physiologic functions of the cell. The aim of the present investigation was to investigate whether hepatotoxic effects of nitrosamine and colchicine can be detected through changes in the cytokeratin filament system which is an important component of the cytoskeleton. Groups of 10 male and 10 female newborn BALB/c mice were treated with either 25 micrograms dimethylnitrosamine (DMN) injected intraperitoneally on the day of birth; or with a daily subcutaneous injection of 0.12 micrograms/kg b.w. colchicine starting at ten weeks of age. A third group of mice served as untreated controls. All animals were held under standard laboratory conditions until necropsy at 16 weeks of age. The group injected with DMN received 0.05% phenobarbital with their drinking water after weaning. The histologic changes in the liver tissue were characterized by light microscopy. Changes of the cytokeratin filaments were visualized by the indirect immunofluorescent technique and quantified by using the image analysing system "IBAS". The cytokeratin filaments in the DMN group were markedly increased in amount and had a variety of morphological alterations. These effects could be measured quantitatively and did not indicate any sex-dependent behavior. The colchicine group did not display any structural changes in the cytokeratin filaments but sex-dependent changes in the amount of keratin material was revealed by image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actin Cytoskeleton; Adenoma; Animals; Biomarkers, Tumor; Colchicine; Dimethylnitrosamine; Female; Image Processing, Computer-Assisted; Keratins; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence

Forty-two renal cell carcinomas, one oncocytoma and normal renal tissue were studied for the presence of cytokeratins and vimentin. The investigations were performed by immunofluorescence microscopy applying a panel of mono- and polyclonal antibodies to intermediate filament proteins. In all tumours except chromophobic renal cell carcinoma (CRCC) and oncocytoma a co-expression of cytokeratins and vimentin could be shown. The intermediate filament expression was often, however, very heterogeneous particularly with respect to the distribution of cytokeratins and vimentin, to the clonality of the antibodies used and to the tumour areas studied. The latter could be impressively demonstrated by examining a whole tumour. In CRCC and oncocytoma all tumour cells expressed cytokeratins and, in addition, single tumour cells also expressed vimentin. In normal renal tissue we could show vimentin-positive epithelia of proximal and distal tubules, which is reported for the first time.

Topics: Adenoma; Carcinoma, Renal Cell; Cytoskeletal Proteins; Desmoplakins; Epithelium; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Vimentin

The distribution of simple epithelial (K8/18/19) and basal (myoepithelial) (K5/14) keratins, alpha-smooth-muscle actin, vimentin, collagen IV and laminin in normal mammary glands and in benign proliferative lesions was studied using monoclonal antibodies (mAbs). These antibodies (Abs) identified myoepithelial cells and luminal cells specifically. In lesions with adenosis and papillomas, the two-layered formation resembled that of normal glands with a purely myoepithelial-epithelial differentiation. In scleradenotic lesions, the main cell was of myoepithelial immunophenotype with intermixed trabecular-tubular proliferations of simple-type epithelium. The sclerosis seems to be the result of an irregular basal lamina synthesis by the myoepithelial cells. In contrast to these lesions, epitheliosis represents a purely intraluminal cell proliferation of clearly simple epithelial immunophenotype and of cells with a basal keratin phenotype, lacking myoepithelial differentiation antigen actin. The basal keratin type epithelium may represent post-stem or intermediate cells developing into luminal epithelium. Epitheliosis appears to be a purely epithelial hyperplasia with striking similarity to the regeneration of normal breast epithelium. The different proliferative patterns may give an explanation for differences in potential cancer risks of patients with these lesions.

Topics: Actins; Adenoma; Antibodies, Monoclonal; Biomarkers, Tumor; Breast; Breast Neoplasms; Cell Division; Collagen; Epithelium; Female; Humans; Keratins; Laminin; Muscles; Papilloma; Vimentin

Sixty-six renal cortical epithelial tumors were classified by light and electron microscopy into 18 oncocytomas and 48 renal carcinomas, and their pattern of cytokeratin and vimentin reactivity was evaluated by immunoperoxidase using paraffin-embedded tissue. We found by electron microscopy that most oncocytomas (11 of 15) contain globular filamentous bodies that consist of a complex of intermediate filaments and organelles. These structures were found to correlate on immunohistochemistry with a discrete punctate cytoplasmic pattern of cytokeratin reactivity, provided the antibody preparation contained specificity for cytokeratins 8 and 18. A similar punctate finding was not observed in four oncocytomas nor in the 48 renal carcinomas. Although 11 oncocytomas failed to express vimentin, seven tumors showed focal reactivity restricted to rare individual cells in areas of sclerosis (five tumors) or in cell clusters bordering central scars (two tumors). We conclude that many oncocytomas contain a potentially diagnostically useful punctate pattern of cytokeratin reactivity and that focal vimentin reactively may be observed in otherwise typical oncocytomas, restricted to tumor cells appearing to be undergoing atrophy.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Inclusion Bodies; Keratins; Kidney Neoplasms; Male; Microscopy, Electron; Middle Aged; Vimentin

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells.

Topics: Adenoma; Adult; Female; Gallbladder Neoplasms; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Middle Aged; Molecular Weight

The immunohistochemical localization of five antibodies against carcinoembryonic antigen (CEA), CA19-9, keratin, alpha-tubulin and secretory component (SC) was investigated in 14 lesions of adenocarcinoma (AC), 22 of adenoma with high-grade atypia (AH), 50 of adenoma with low-grade atypia (AL), and 15 of non-neoplastic mucosa (NNM) of the large intestine. The positive patterns for each staining were divided into three categories (patterns 1, 2, and 3). All neoplastic lesions (AC, AH and AL) were positive for CEA, while 85.7% of AC, 36.4% of AH and 6.0% of AL showed strongly positive staining (pattern 3). 78.6% of AC and 54.5% of AH were positive for CA19-9 in comparison to 20.0% of AL. For keratin, more than 95% of the neoplastic lesions were positive, while 78.6% of AC, 27.3% of AH and 22.0% of AL showed strongly positive staining (pattern 3). For alpha-tubulin, more than 85% of neoplastic lesions were positive, while 50.0% of AC, 36.3% of AH and 26.0% of AL showed strongly positive staining (pattern 3). For SC, in contrast, 42.9% of AC, 27.3% of AH and 8.0% of AL were negative, but 93.3% of NNM were positive. It was concluded that the positive staining rate, especially the rate of pattern 3 for each antibody correlated with the degree of atypia of the colorectal neoplastic lesions (AC, AH and AL).

Topics: Adenocarcinoma; Adenoma; Antibodies, Anti-Idiotypic; Antibodies, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Colorectal Neoplasms; Cytoskeleton; Humans; Keratins; Secretory Component; Staining and Labeling; Tubulin

Sixteen growth hormone (GH)-producing pituitary adenomas were studied for the expression of glycoprotein hormone subunits and cytokeratin by light microscopic immunohistochemistry. Cytokeratin immunoreactivity was demonstrated in all adenomas, but its intracytoplasmic distribution showed two distinct patterns; a prominent, dot-like pattern and a diffuse, perinuclear pattern. Seven adenomas (type 1) were exclusively composed of cells with cytokeratin in a dot-like pattern, whereas 9 adenomas (type 2) comprised of cells with cytokeratin of perinuclear distribution. The expression of alpha-subunit of glycoprotein hormone was significantly different between the two types of adenomas; 8 of 9 adenomas of type 2 contained many alpha-subunit immunoreactive cells but none of type 1 adenomas showed any immunoreactivity. Only a small number of adenoma cells were positive for beta-subunit of thyrotropin stimulating hormone in 3 adenomas of type 2. beta-subunits of follicle stimulation hormone and luteinizing hormone were negative in all adenomas. These findings suggest that the expression of glycoprotein hormone subunits in GH-producing adenomas may be closely linked to their types distinguishable by the cytokeratin distribution pattern.

Topics: Adenoma; Adult; Aged; Female; Glycoproteins; Growth Hormone; Hormones; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pituitary Neoplasms; Tissue Distribution

Immunohistochemical study was carried out in a case of adenomatoid tumor of the uterine corpus. The patient was a 35-year-old female. The tumor showed classical histochemical and immunohistochemical findings of mesothelioma, i.e., presence of hyaluronic acid on the cellular surface and cytokeratin in the cytoplasm. In addition, the tumor showed positive reaction to anti-vimentin. Furthermore, absence of Ber-Ep4 supports mesothelial origin of this tumor. EMA reaction was reported only in one case in the literature. The result was negative as in our case. Therefore, it was suggested that at least some of the adenomatoid tumor were negative for EMA as in malignant mesothelioma, although this tumor was benign. Therefore, it was suggested that loss of EMA in mesothelial tumor was not always related to anaplastic change.

Topics: Adenoma; Adult; Female; Humans; Hyaluronic Acid; Immunohistochemistry; Keratins; Mesothelioma; Uterine Neoplasms; Vimentin

Seventy-five formalin-fixed and 18 alcohol-fixed pituitary adenomas were studied immunohistochemically using antibodies to keratin, vimentin, neurofilaments (NFs), glial fibrillary acidic protein, desmin, actin, S-100 protein and a variety of pituitary hormones. The pituitary adenoma cells were positive for keratin, vimentin and NFs (68 kDa and 160 kDa) and in a few instances there was co-expression of these three types of intermediate filaments (IMFs). The pattern of keratin-specific staining showed diffuse cytoplasmic or patchy paranuclear reactivity and of NF- or vimentin-specific staining showed fibrillar or patchy paranuclear reactivity. The patchy staining seemed to decorate the fibrous body. There was no correlation between the distribution of IMFs and pituitary hormones in pituitary adenomas except that melanocyte-stimulating-hormone-positive reactivity was limited to the NF-positive adenomas. The pattern of IMF staining did not depend on hormone production in adenomas.

Topics: Adenoma; APUD Cells; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Pituitary Neoplasms; Vimentin

A series of adrenal cortical adenomas (ACA) and carcinomas (ACC), as well as normal adrenal cortex have been studied by a panel of 11 antibodies to characterize antigenic changes that may distinguish these morphologically similar entities. Normal adrenal cortex and ACA express low-molecular weight cytokeratin intermediate filaments. However, none of the six primary or seven metastatic ACCs were found to express detectable levels of cytokeratins. In contrast, vimentin was seen in all ACCs studied and was heterogeneously expressed by ACAs. However, its expression was usually confined to stromal elements of the normal adrenal cortex. We conclude that adrenal cortical cells undergo characteristic changes in intermediate filament expression during the process of neoplastic conversion and malignant transformation. Undetectable expression of cytokeratins and strong expression of vimentin is associated with malignant adrenal cortical lesions. In addition, we examined the antigenic phenotype of a series of primary renal cell carcinomas (RCC). Renal cell carcinomas express cytokeratins, while ACCs do not. The majority of primary RCCs express Lewis blood group isoantigens (most commonly Lewis X), while ACAs and ACCs do not. The panel of antibodies described here may help to distinguish morphologically similar lesions of like histogenesis (ACAs vs. ACCs) and lesions of different histogenesis (adrenal vs. renal) on the basis of their composite antigenic phenotypes.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Antigens; Carcinoma; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Isoantigens; Keratins; Kidney Cortex; Kidney Neoplasms; Vimentin

Three patients are described who presented with a large colonic adenoma in which a solid, undifferentiated carcinomatous component was found on microscopic examination. Despite small size (1.0 and 1.5 cm) and submucosal location in two cases, the tumours had metastasized to regional lymph nodes and the liver and death ensued at 4, 11 and 18 weeks after surgery. Immunocytochemistry was positive for carcino-embryonic antigen, low molecular weight cytokeratins and neuron specific enolase in all three cases and scanty dense core granules of neurosecretory type were found in one of two examined by electron microscopy. These 'neuroendocrine' carcinomas are compared with 'pure' adenomas and 'ordinary' poorly differentiated adenocarcinomas of the colon from which they differ, mainly by lack of glandular differentiation and mucus secretion, although two adenocarcinomas also showed patchy reactivity for neuron specific enolase. The term 'neuroendocrine' may be disputed but is now well established to describe a tumour that runs a uniquely aggressive course and for which radical surgery alone cannot provide a cure.

Topics: Adenocarcinoma; Adenoma; Aged; Aged, 80 and over; Carcinoma, Small Cell; Cell Differentiation; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase

Fifty-eight salivary gland pleomorphic adenomas and 5 normal salivary glands were studied immunohistochemically with respect to intermediate filaments (keratin, desmin, and vimentin), actin and S-100 protein to observe the cellular differentiation of these tumor cells. Normal myoepithelial cells showed positive immunostaining for actin, vimentin and S-100 protein. Pleomorphic adenomas expressed keratin, vimentin and S-100 protein to various degrees, but only a few tumor cells of pleomorphic adenoma revealed actin. The results indicate that the tumor cells of pleomorphic adenoma show a bipolar differentiation capability of both epithelial and mesenchymal origins, although normal myoepithelial cells show only mesenchymal characteristics. The findings also support previous reports using light and electron microscopy, and also contribute to more precise diagnosis and a better understanding of the histogenesis of this tumor.

Topics: Actins; Adenoma; Desmin; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling; Vimentin

There are a number of benign, small-acinar lesions in the prostate gland that may be difficult to differentiate from small-acinar adenocarcinoma. An important diagnostic criterion in this differentiation is the loss of the basal layer in small-acinar adenocarcinoma and its preservation in benign conditions. A monoclonal antibody to high-molecular-weight cytokeratins (34 beta E12) has been shown to stain these basal cells preferentially. To assess the usefulness of this antibody in distinguishing benign from malignant small-acinar lesions, we examined 21 cases of small-acinar adenocarcinoma and 47 examples of benign lesions, which included atypical adenomatous hyperplasia, atrophy, post-sclerotic hyperplasia, basal cell hyperplasia, and fibroepithelial nodule. Positive staining with 34 beta E12 was seen in 13/13 cases of atypical adenomatous hyperplasia, although in some cases the staining was weak and focal. Positivity with 34 beta E12 was also demonstrated in all other benign lesions studied. All 21 cases of small-acinar adenocarcinoma showed no reactivity with 34 beta E12. The results suggest that 34 beta E12 is of value in distinguishing between well-differentiated, small-acinar prostatic adenocarcinoma and its mimics. However, care is needed in interpretation of staining in formalin-fixed material due to the variable reactivity, particularly in cases of atypical adenomatous hyperplasia.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Atrophy; Diagnosis, Differential; Evaluation Studies as Topic; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostate; Prostatic Diseases; Prostatic Neoplasms; Staining and Labeling

Archival paraffin sections from normal salivary gland tissue and salivary gland neoplasms were stained by immunoperoxidase technique with a well characterized cytokeratin antibody (PKK1). In normal parotid tissue, myoepithelial cells and peripheral cells of larger ducts were selectively stained. In pleomorphic adenomas, most cells were stained, the staining being somewhat stronger towards the duct lumina. In basal cell adenomas, only cells adjacent to the duct lumina were stained where a differentiation of cells into peripheral and ductal was seen. In adenolymphomas basal cells were stained, and in oncocytomas small elongated cells reacted with the PKK1 antibody. Only a few duct cells in an acinic cell carcinoma were reactive and in mucoepidermoid carcinoma, peripheral epidermoid cells were strongly stained. In adenoid cystic carcinoma, mostly duct cells were stained whereas the peripheral ones remained unstained. Although the intermediate filament protein expression is very stable during tumorigenesis, the staining with the presently used monoclonal antibody in salivary gland neoplasms differed markedly from what could be expected according to current views on the participation of this cell type. This supports our view that cells in tumors should be characterized on the basis of their staining, i.e. state of differentiation and not on their presumed histogenesis.

Topics: Adenoma; Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Salivary Gland Neoplasms

The cellular phenotype of 34 primary adenoid liver tumours induced in rats with N-nitrosomorpholine was studied by immunocytochemical and electron microscopical methods in order to elucidate the histo- and cytogenesis of these tumours. Three types of ducts were distinguished in the adenoid liver tumours at the ultrastructural level being characterized as of hepatocellular, transitional and cholangiocellular phenotype. The transitional cells took an intermediate position between the hepatocellular and the cholangiocellular phenotype. Frequent features of the hepatocyte-like differentiation were large round nuclei with a dispersed chromatin, glycogen-associated ER complexes, peroxisomes and the formation of bile canaliculi. Evidence for the relationship to bile ductular cells was provided by the regular association with a basement membrane, the (inconstant) positive immunohistochemical reaction for cytokeratin polypeptide KA-4, a poorly developed ER and small mitochondria. An additional finding in the ducts with a transitional cellular phenotype was the selective accumulation of mast cells integrated into the epithelium. Intimate associations between cells of the hepatocellular, transitional and cholangiocellular phenotype were observed at the light and electron microscopic level. The results suggest that a transdifferentiation (metaplasia) from cells with a hepatocellular to those with a transitional or cholangiocellular phenotype takes place in many liver tumours.

Topics: Adenoma; Animals; Immunohistochemistry; Inclusion Bodies; Keratins; Liver Neoplasms, Experimental; Male; Metaplasia; Microscopy, Electron; Morpholines; Phenotype; Rats; Rats, Inbred Strains

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenofibroma; Adenoma; Antibodies, Monoclonal; Brenner Tumor; Carcinoma; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms

A rare case of granular cell ameloblastoma in the anterior mandible of a 59-year-old man has been studied by light and electron microscopy. In some areas, the tumor was very similar to an oncocytoma (oxyphilic adenoma). Almost all tumor cells were full of eosinophilic granules, whereas in the common type of granular cell ameloblastoma, only the cells located in the central portion of the tumor are granular.

Topics: Adenoma; Ameloblastoma; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Diagnosis, Differential; Epithelium; Humans; Keratins; Male; Mandibular Neoplasms; Middle Aged

Twelve cases of monomorphic adenoma of the salivary glands were histologically reclassified and their immunohistochemical reactivity for S-100 and cytokeratin was correlated. All patients underwent a benign clinical course. Individual tumors were well encapsulated and frequently showed a focal cystic change. Histologically, 9 cases were of the epithelial basaloid cell type and 3 cases were of the myoepithelioma variant. About one half of the epithelial type featured a mixture of trabecular and tubular patterns. The immunoreactivity to S-100 and cytokeratin varied. All basaloid cell adenomas were positive for cytokeratin, while S-100 positivity was found mostly in the stroma along with the varied reaction and intensity in the epithelial nests. In myoepitheliomas, cytokeratin was totally negative and S-100 was positive in 2 of 3 cases. The above findings suggest that the degree of participation of myoepithelial cells determines the phenotypic expression of monomorphic adenomas, and supports the hypothesis that the basaloid cell and myoepithelial types may be located on extreme ends of the same tumor spectrum with a wide range of pleomorphic adenoma in-between.

Topics: Adenoma; Adult; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Salivary Gland Neoplasms

Using immunoperoxidase staining of monoclonal antibody 312C8-1 against 51,000 dalton human keratin polypeptide, immunolocalization was observed in frozen sections of normal tissue and mammary tumours of adult female mice and rats. In normal tissue, the epitope was recognized in myoepithelial cells of the mammary, sweat and salivary glands, and in basal and suprabasal cells of the epidermis. However, the antibody did not react with luminal epithelial cells of the above glands or with mesenchymal cells. In spontaneous mammary tumours of mice, marker-positive tumour cells were distributed only in the outer layer of adenocarcinoma Type A, while they were scattered in some foci of adenocarcinoma Type B, and encircled the epithelial foci of pregnancy dependent tumours (plaque). All layers of epidermoid structures in adenoacanthoma revealed positivity. In rat mammary tumours induced by local dusting with 7, 12-dimethylbenz(a)anthracene (DMBA) powder, the staining pattern of benign tumours was comparable to that of the normal mammary gland. But, in addition to basally situated cells, marker-positive tumour cells were found scattered in the foci of adenocarcinoma, and were not restricted to basal cells in squamous cell carcinoma. The marker was not found in sarcomatous tissue. This antibody can therefore also be applied to rodents, and the staining pattern can be used to identify the epithelial subclass specific marker in normal tissue and in mammary tumours.

Topics: Adenocarcinoma; Adenoma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Female; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred Strains; Rats; Rats, Inbred Strains

We have studied three examples of benign thyroid tumours which conform to the lesion recently described as hyalinizing trabecular adenoma. The prominent feature of this trabecular epithelial lesion is the extracellular deposition of an eosinophilic material that does not show the features of amyloid; the epithelial cells may be elongated, sometimes radially arranged around the eosinophilic material. All three tumours showed positive immunocytochemical staining for thyroglobulin, keratin, chromogranin and neuron-specific enolase. One tumour showed isolated cells with immunoreactivity for somatostatin, argyrophil cytoplasmic granularity with the Grimelius technique, and ultrastructurally demonstrable cytoplasmic electron-dense endocrine granules. The hyaline extracellular material in all three tumours showed strong immunoreactivity for both type IV collagen and laminin. Previous radiation may be important in the causation of this tumour, and it shows a frequent association with severe thyroiditis. We conclude that the main histological feature of this lesion, the hyaline material, is due to the overproduction of a basement membrane-like material by the neoplastic follicular cells. The presence in one tumour of evidence of endocrine differentiation may reflect the potential for follicular cells to show biphasic differentiation, a feature which may be more frequent than has been previously recognized. Several of the other features of this tumour--for example the frequent intranuclear cytoplasmic inclusions--may lead to diagnostic problems, and the entity deserves wider recognition.

Topics: Adenoma; Aged; Chromogranin A; Chromogranins; Collagen; Female; Humans; Immunohistochemistry; Keratins; Laminin; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase; Somatostatin; Thyroglobulin; Thyroid Neoplasms

We present a case of tubular adenomatous metaplasia (nephrogenic adenoma) arising within a urethral diverticulum in a woman complaining of a vaginal mass with dyspareunia. This lesion, which uncommonly affects the urethra, may clinically manifest as a gynecologic condition and mimic a low-grade adenocarcinoma on pathologic assessment. Criteria for diagnosis and current concepts of pathogenesis are discussed. Our findings, including an immunocytochemical work-up, support the concept of a reactive metaplastic response rather than nephrogenic differentiation.

Topics: Adenoma; Adult; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Pregnancy; Pregnancy Complications, Neoplastic; Urethral Neoplasms

Keratin expression with the use of chain-specific monoclonal antikeratin antibodies was investigated in normal thyroid tissue (n = 4), colloid nodules (n = 19), follicular thyroid adenomas (n = 18), follicular carcinomas (n = 10), and papillary carcinomas (n = 12). Frozen sections were stained with monoclonal antibodies M20 (keratin 8), M9 (keratin 18), and LP2K (keratin 19) with the use of the indirect immunoperoxidase technique. The immunohistochemical findings showed that the expression of keratins 8 and 18 was equally extensive in all normal, benign, and malignant lesions tested. In contrast, different staining patterns were observed with the use of monoclonal antibody to keratin 19. Follicular carcinomas were only focally stained with this antibody or were not reactive at all. Keratin 19, however, was present in all the tumor cells of papillary tissues and in a moderate amount of cells of nonneoplastic thyroid lesions and follicular adenomas. In papillary carcinoma, an identical homogeneous expression of keratin 19 was observed in both papillary and follicular structures, which suggests a common cellular origin. These results show that immunohistochemical staining with the use of monoclonal antibody against keratin 19 is useful to distinguish papillary thyroid carcinomas from follicular adenomas and follicular thyroid carcinomas.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Carcinoma, Papillary; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Thyroid Neoplasms

An immunohistochemical study of 34 pleomorphic adenomas of the major salivary glands demonstrated phenotypic differences among the various morphologic regions in these tumors. The phenotypes expressed were comparable to those of normal salivary gland cells. In the normal glands, myoepithelial cells were immunoreactive for glial fibrillary acidic protein (GFAP), S-100 protein, and keratin; acinic cells exhibited strong, predominantly nuclear S-100 staining and weaker keratin staining; intercalated ducts had both cytoplasmic and nuclear S-100 positivity; and several epithelial antigens were observed throughout the ductal system. In the tumors, the presence of classic epithelial markers (including carcinoembryonic antigen, epithelial membrane antigen, secretory component, and keratin) in the luminal cells of ducts and the intense immunoreactivity with GFAP (with weaker keratin and S-100 staining) in periductal and stromal cells indicated distinct epithelial and myoepithelial differentiation. Solid epithelioid areas consisted phenotypically of intercalated duct/acinic cells and/or myoepithelial cells, the former exhibiting predominant nuclear S-100 positivity. The presence of GFAP-like immunoreactivity in normal myoepithelial cells strongly supports the extensive involvement of this cell in pleomorphic adenomas. The spectrum of phenotypes expressed adds weight to existing evidence for pleomorphism rather than a mixed origin of this tumor. The combination of keratin, S-100, and GFAP immunostaining is particularly useful in identifying the component cells in pleomorphic adenomas of the salivary glands.

Topics: Adenoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Phosphopyruvate Hydratase; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands

The intermediate filament profile of adrenal cortex and its related tumours has been evaluated. Most adrenocortical cells contained cytokeratin 8 and 18 as demonstrated by monoclonal antibodies CAM 5.2, M20, M9 and RGE53. Cytokeratin immunoreactivity was not confined to a functional zone of the adrenal cortex. Only a small number of the adrenocortical cells showed vimentin immunoreactivity. From normal adrenal cortex through adenomas, to carcinomas, there is a progressive decrease or even loss of cytokeratin immunoreactivity and an increase in vimentin immunoreactivity. Aberrant cytokeratin expression was not found in adrenocortical adenomas and carcinomas with the antibodies used. Awareness of the possible absence of cytokeratin immunoreactivity in adrenocortical carcinomas is important whenever antibodies to cytokeratins and vimentin are used for diagnostic purposes in poorly differentiated neoplasms.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Adult; Aged; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Vimentin

A comparative immunohistochemical study of intermediate filament expression in normal parotid glands and pleomorphic adenomas (PA) was performed using material fixed in a modified methacarn fixative. The normal myoepithelial cells of acini stained only with monoclonal antibodies 312C8-1 (cytokeratin (CK) 14) and 4.62 (CK 19) while myoepithelial/basal cells of ducts also reacted with antibodies 8.12 (CK 13, 16), 8.60 (CK 10, 11, +/- 1), and PKK1 (CK 7, 8, 17, 18). Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60. In PA, tumour cells at the periphery of ducts, in solid areas, and at the edge of myxoid regions all had CK profiles similar to normal myoepithelial/basal cells except that antibody 4.62 was generally negative. Vimentin and glial fibrillary acidic protein (GFAP) were uniformly negative in normal parotids but showed variable (often strong) reactivity with some cells in chondroid, myxoid and solid areas of PA. A surprising feature of most PA was the variability of CK subtype expression not only from one case to another but also within morphologically similar areas of the same specimen. These results suggest that the morphology of PA is the result of diversity of tumour cell differentiation rather than the processes implicit in a reserve cell histogenetic model.

Topics: Adenoma; Cytoskeleton; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intermediate Filaments; Keratins; Parotid Gland; Parotid Neoplasms

An immunohistochemical study on keratin, vimentin, and myosin was performed in 117 specimens of human salivary gland under normal and several neoplastic conditions. In normal glands, positive immunostaining for keratin was observed in the inner cells of all ductal systems, whereas myosin and vimentin were the cytoskeletal components of myoepithelial cells. In pleomorphic adenoma, the inner cells showing a tubular pattern demonstrated positive immunostaining for keratin, and the outer cells as well as the neoplastic cells with a solid and myxoid pattern exhibited positive immunostaining for all antibodies. Monomorphic tubular and trabecular adenoma, and adenolymphoma showed positive immunostaining for keratin, although one case of tubular adenoma exhibited positive immunostaining for all antibodies. Squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid tumor showed positive immunostaining only for keratin, but one case of adenocarcinoma, two cases of adenoid cystic carcinoma, and clear cell tumor disclosed positive immunostaining for keratin and vimentin.

Topics: Adenoma; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Myosins; Salivary Gland Neoplasms; Salivary Glands; Vimentin

A case of bile duct adenomas in association with heterozygous (MZ) deficiency of alpha 1-proteinase inhibitor (API) is presented. The salient features were the presence of large API-containing globules in the adenomatous tissue and only minimally, in granular form, in hepatocytes. alpha 1-Proteinase inhibitor was not demonstrated in portal bile ducts entrapped in the adenomatous tissue or in bile ducts present in the liver parenchyma. Bile duct markers such as cytokeratin and carcinoembryonic antigens were present in the adenomatous tissue and also in the normal bile ducts, but not in the hepatocytes, suggesting that the adenomatous structures are ductular in origin, and probably not from ductular metaplasia of liver cells. Accumulation of API is postulated to be a triggering factor in neoplastic transformation.

Topics: Adenoma; Adult; alpha 1-Antitrypsin; Bile Duct Neoplasms; Blood Proteins; Carcinoembryonic Antigen; Heterozygote; Humans; Immunoenzyme Techniques; Keratins; Male; Protease Inhibitors

The histogenesis of renal cell carcinoma and oncocytoma is controversial. We compared immunohistochemical profiles of normal kidney, nine carcinomas, and six oncocytomas. Carcinomas and oncocytomas expressed the following antigens respectively: proximal tubule--Uro 3 (56 & 67%), alpha-1-antitrypsin (89 & 50%); proximal and distal tubule--Uro 10 (67 & 83%); distal tubule--B2-microglobulin (100 & 100%); distal/medullary tubule--epithelial membrane antigen (89 & 83%), neuron-specific enolase (78 & 100%), glandular cytokeratin (78 & 100%), epidermal keratin (67 & 67%); and medullary tubule--Uro 8 (89 & 83%). All tumors, except one oncocytoma, had at least one positive reaction for each antigen group. Oncocytomas predominantly stained for distal/medullary tubular antigens; none showed a predominance of proximal tubular antigens. Carcinomas also demonstrated largely distal/medullary tubule antigens; 44% showed prominence of proximal tubular antigens as well. Assignment of an exclusive proximal, distal or medullary tubule origin to renal neoplasms does not appear valid. Divergent histogenesis from a precursor stem cell is likely.

Topics: Adenoma; Antigens; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules; Neoplastic Stem Cells; Vimentin

Malignant cell lines related to mouse lung alveologenic carcinoma have been established from urethane-induced tumors and after in vitro spontaneous transformation of preneoplastic cell lines. Both the chemically and spontaneously transformed cell lines formed invasive, poorly differentiated carcinomas with secondary lung deposits when implanted subcutaneously in immune-suppressed mice. They differed from the related preneoplastic cell line in coordinately exhibiting anchorage-independent growth, reduced epidermal growth factor receptor activity and absence of pericellular fibronectin. These data suggest that similar molecular events may occur in type 2 pneumocyte-related cells in order to generate mouse lung alveologenic adenomas and carcinomas by both spontaneous and chemical carcinogen induction mechanisms. A reduced level of pericellular fibronectin was also demonstrated in an in situ compressive urethane-induced mouse lung adenoma. Loss of pericellular fibronectin may therefore be an early and persistent phenotypic alteration during transformation to the alveologenic adenoma and carcinoma.

Topics: Adenoma; Animals; Cell Line, Transformed; Cell Transformation, Neoplastic; Female; Fibronectins; Keratins; Lung Neoplasms; Mice; Mice, Inbred BALB C; Pulmonary Alveoli; Urethane

A tumor arising in the pituitary fossa and having some of the histological and ultrastructural features of a recently described tumor, purportedly originating from the folliculo-stellate cells of the anterior pituitary, is presented. The results of our ultrastructural and immunohistochemical studies, however, favored a meningeal origin and suggested that the neoplasm was most likely a secretory meningioma.

Topics: Adenoma; Diagnosis, Differential; Female; Humans; Keratins; Membrane Glycoproteins; Meningeal Neoplasms; Meningioma; Middle Aged; Mucin-1; Pituitary Neoplasms; Vimentin

Cytokeratins were studied by immunocytochemical techniques at light and electron microscopy on 12 normal pituitary glands, 30 pituitary adenomas and three craniopharyngiomas. The results are presented in relation to clinical and biochemical features and new information on the subcellular localisation of cytokeratins in pituitary cells is discussed.

Topics: Adenoma; Adolescent; Adult; Aged; Female; Fetus; Histocytochemistry; Humans; Immunologic Techniques; Keratins; Male; Middle Aged; Molecular Weight; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Neoplasms; Pregnancy

Topics: Adenoma; Carcinoma; Cytoskeleton; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Salivary Gland Neoplasms; Vimentin

We examined the expression of the diverse cytokeratin (CK) polypeptides as well as vimentin in human renal cell carcinomas of various subtypes and in renal oncocytomas by applying both two-dimensional gel electrophoresis and immunocytochemistry by using polypeptide-specific monoclonal antibodies. The tumors were classified according to the guidelines of the World Health Organization, with some modifications based primarily on recently proposed cytomorphological criteria. All clear cell carcinomas (G I, G II; N = 20) co-expressed CKs nos. 8 and 18, and vimentin, with CK no. 19 being present in 13 of the 20 cases and exhibiting a heterogeneous distribution. Dedifferentiated carcinomas (G III; N = 8) also co-expressed CKs nos. 8 and 18 as well as vimentin, but in addition, exhibited CK no. 19 and, in many cases, CK no. 7; in 1 case, only vimentin was expressed. Both eosinophilic-granular (N = 3) and basophilic (small cell cuboidal; N = 6) carcinomas contained CKs nos. 8 and 18, and the co-expression of vimentin was a consistent feature of these tumors; CK no. 19 was found in all of these cases, while CK no. 7 was present in the majority. In chromophobe cell carcinomas (N = 8), in contrast to all of the other carcinoma types, no vimentin was detected in the tumor cells, with only CKs nos. 8, 18, and to a variable extent 7, being present. Similarly, oncocytomas (N = 8) lacked vimentin and exhibited only CKs nos. 8 and 18. Conspicuous scattered CK no. 19-positive cells were found in these two last tumor types. No CK polypeptides other than simple-epithelium-type CKs (nos. 7, 8, 18, and 19) were detected in any of the tumors studied. These results indicate that, in renal cell tumors, the expression of intermediate-filament proteins is strikingly correlated with the specific morphologic appearance. While the co-expression of CKs nos. 8 and 18 and vimentin was a surprisingly consistent feature of the most common subtypes of renal cell carcinomas, CK no. 19 exhibited remarkable heterogeneity of expression both within individual tumors and between different tumors, the expression patterns of this CK being correlated to the tumor subtypes. The consistent absence of vimentin in chromophobe cell carcinomas and oncocytomas makes it possible to define these as a separate class of renal cell tumors. This finding supports the view that chromophobe cell carcinomas represent a distinct tumor entity and points to their close phenotypic relationship to benign oncocytomas as we

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Cell Differentiation; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Male; Middle Aged; Phenotype; Vimentin

Pituitary tumors from 376 patients were investigated, using immunocytochemical techniques at the light and electron microscopic level, and autoradiography combined with immunocytochemistry for localizing somatostatin (SRIH) receptors. Prolactinomas, growth hormone-secreting adenomas causing acromegaly, and hormonally inactive adenomas were most frequently observed (153, 86, and 90 tumors, respectively). Among the latter, we could distinguish "alpha-only adenomas," many of which were oncocytomas. At the light and electron microscopic levels, cells containing (and presumably producing) simultaneously both prolactin and growth hormone, and cells containing exclusively either prolactin or growth hormone, could be demonstrated. In addition, a highly variable number and distribution of SRIH receptors could be shown in tumors secreting prolactin, growth hormone, and in tumors not associated with symptoms caused by inappropriate hormone secretion. The systematic combination of clinical, radiological, and biological techniques has currently brought great progress in the behavior and therapeutic concepts of pituitary lesions, and promises new achievements in the near future.

Topics: Adenoma; Female; Growth Hormone; Hormones; Humans; Immunochemistry; Keratins; Male; Pituitary Neoplasms; Prolactin; Receptors, Neurotransmitter; Receptors, Somatostatin

Topics: Adenoma; Dendritic Cells; Epithelial Cells; HLA-D Antigens; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Parotid Neoplasms; S100 Proteins; Salivary Glands

The diagnosis of adrenocortical carcinoma (ACC) is often difficult, because this tumor may present with direct extension into adjacent renal parenchyma or with metastatic disease. Renal cell carcinoma and other histologically similar tumors are potentially confused with ACC by conventional light microscopy, and their separation from the latter is often impossible without the aid of additional studies. Furthermore, the distinction between adrenal cortical adenoma and ACC may also be problematic. Because of these factors, the authors studied 10 cases each of ACC, adrenocortical adenoma, and renal cell carcinoma (RCC) immunohistochemically, in an attempt to develop objective parameters which may aid in this differential diagnostic dilemma. Nontrypsinized, formalin-fixed, paraffin-embedded specimens were used in all cases, and tissue from the adrenocortical tumors was also studied for intermediate filament content after protease digestion. All 20 nontrypsinized adrenocortical neoplasms were positive for vimentin, but not for cytokeratin, epithelial membrane antigen, or blood group isoantigens. Conversely, each of 10 cases of RCC expressed epithelial membrane antigen, cytokeratin, and blood group isoantigens, but none was immunoreactive for vimentin. Two adrenocortical carcinomas and three adenomas manifested cytokeratin positivity after trypsin digestion. There were no significant differences between the immunostaining profiles of ACC and adrenocortical adenoma, which suggest that this distinction must still rely upon clinical and morphologic criteria.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adult; Aged; Antigens; Blood Group Antigens; Carcinoma; Carcinoma, Renal Cell; Cell Nucleolus; Cell Nucleus; Child, Preschool; Cytoplasm; Diagnosis, Differential; Epithelium; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Isoantigens; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

Antibodies to intermediate filament proteins react in a tissue-specific manner and can be used to characterize tumor cells present in thin-needle aspirates from solid tumors, from palpable lymph nodes and cells present in samples from peritoneal and pleural effusions. From our studies so far the following conclusions can be drawn: Polyclonal antisera to cytokeratins can identify carcinoma metastases in thin-needle aspirates from palpable lymph nodes and distinguish them from malignant lymphomas and nonmalignant lesions such as chronic lymphadenitis, which show only vimentin-positive cells. Monoclonal antibodies to specific cytokeratin polypeptides are able to distinguish between different types of epithelial tumor metastases, i.e. metastases from adenocarcinomas and metastases from squamous cell carcinomas. Cells present in peritoneal and pleural effusions can be partly characterized using intermediate filament antisera. We have found that metastatic adenocarcinoma cells from breast, ovary, endometrium, cervix, colon and stomach, as well as squamous cell carcinomas and malignant mesothelioma stain specifically with antibodies to cytokeratin while mesenchymally derived tumors such as malignant lymphomas, malignant melanomas, and fibrosarcomas, are positive for vimentin only. Metastatic tumor cells of epithelial origin present in aspirates from human serous body cavity fluids may coexpress vimentin next to their original cytokeratin intermediate filaments. Benign mesothelial cells present in body cavity fluids frequently coexpress cytokeratins and vimentin. Tumor cells present in thin-needle aspirates from solid tumors such as pleomorphic adenomas of the parotid gland can be identified as such because of their typical patterns of intermediate filament (co-)expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Biopsy, Needle; Clinical Laboratory Techniques; Cytoskeletal Proteins; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Lymph Nodes; Neoplasms; Vimentin

Two monoclonal antibodies, KA 1 and KA 4, raised against human epidermis, were biochemically and immunologically characterized and were shown to react with specific cytokeratin polypeptides. On frozen sections of human mammary gland, these antibodies distinguish between myoepithelial and luminal epithelial cells. We present evidence that in these cells KA 1 antibody recognized cytokeratin 5 and KA 4 antibody cytokeratin 19. In normal mammary tissue, KA 4 antibody invariably reacted with the epithelial cells lining the lumina of acini, ductules, ducts, and sinus. In contrast, KA 1 antibody decorated only the myoepithelial and basal epithelial cells of acini, ducts, and sinus. In ductules, however, KA 1 also stained the luminal cells. All 73 invasive lobular and ductal carcinomas studied reacted with KA 4 antibody; five of these were also positive, apparently in the same tumor cells, with KA 1. The tumor cells of in situ carcinomas were also stained in a homogeneous pattern with KA 4 antibody; KA 1 antibody reacted only with the surrounding myoepithelium. In epithelial hyperplasias, the proliferating cells were decorated by KA 1 and KA 4 antibodies in a heterogeneous pattern. Other antibodies were used for comparison. The results are discussed with respect to epithelial differentiation and pathogenesis and to the application of such antibodies for immunohistodiagnosis of mammary lesions.

Topics: Adenoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Epithelium; Female; Fibroma; Fluorescent Antibody Technique; Humans; Keratins; Lactation; Neoplasm Proteins; Papilloma; Pregnancy

Myoepithelial and basal cells were identified by a monoclonal antibody raised against keratin. This antibody (CK B1) which detects myoepithelial cells in normal salivary glands, labels spindle shaped and polygonal cells in pleomorphic adenomas. Most cells in adenoid cystic carcinomas and some basal cells in adenolymphomas were also positive for this antibody. The oncocytic epithelium of adenolymphoma was negative. An inverse reaction was seen with an antibody against cytokeratin 18. The antibody CK B1 seems to be of interest for the detection of myoepithelial/basal cells in salivary glands and salivary gland tumours.

Topics: Adenolymphoma; Adenoma; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Humans; Keratins; Salivary Gland Neoplasms

We describe two novel monoclonal antibodies specific for glial filament protein (GFP), i.e., GF12.23 and GF12.24 (both IgG2a]. These cross-react over a broad range of species with epitopes located in the alpha-helical rod domain typical of all intermediate filament (IF) proteins. These monoclonal antibodies were used, in conjunction with other monoclonal GFP antibodies, rabbit antiserum to GFP, and various antibodies to other cytoskeletal proteins, to examine the occurrence of GFP in cells outside of the central nervous system of rodents, cows, and humans. We detected some scattered GFP-containing cells in the neural sheaths in some species but not in others, and we obtained different results when comparing the rabbit antisera with the monoclonal GFP antibodies. In the enteric glia of rats, we observed GFP-positive cells with all of the antibodies used, whereas in human intestine, the various monoclonal antibodies showed no reaction with any intestinal cells. Similarly, no GFP was detected in surface cells of the lens of cows and rats using any of the GFP antibodies, whereas some reaction was seen in murine lens tissue. We were also unable to detect GFP-positive cells in human, bovine, or rat liver with any of the monoclonal antibodies, which is in contrast to the reactivity of the rabbit GFP antisera with some stellate perisinusoidal cells of rat but not bovine or human liver. The possible reasons for the discrepancies between the different species and the different antibody preparations used are discussed. In addition, using double-label immunofluorescence microscopy, we showed that normal human parotid glands contain a certain type of epithelial cell that co-expresses cytokeratins and desmosomal proteins with GFP. The histological distribution of these GFP-positive cells suggests that they represent a subset of the myoepithelial cells present in this tissue. Cells co-expressing cytokeratins and GFP - in some cases, apparently together with vimentin as the third IF protein present - were also identified in tumors derived from this salivary-gland epithelium, i.e., pleomorphic adenomas, in which GFP-positive cells were relatively frequent in the myxoid and chondroid components, thus confirming the work of other investigators. Possible implications for the concept of histogenesis of these tumor cells are discussed, as are possible mechanisms resulting in the co-expression of IF proteins.

Topics: Adenoma; Adenoma, Pleomorphic; Animals; Antibodies, Monoclonal; Cattle; Cross Reactions; Epithelium; Epitopes; Eye; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Guinea Pigs; Humans; Keratins; Microscopy, Fluorescence; Myelin Sheath; Rats; Salivary Glands; Species Specificity; Vimentin

Cells of the normal colonic mucosa express several types of cytokeratins, the characteristic intermediate filament proteins of epithelial cells. An immunohistochemical study was designed to examine the expression of two distinct groups of cytokeratins, recognized by monoclonal antibodies AE1 and AE3, in the colonic mucosa and to compare the findings with those obtained with a large number of polypoid lesions (adenomatous and hyperplastic) and carcinomas of the colon. AE1 and AE3 immunostaining was found in the surface epithelium and upper portions of the crypts of Lieberkühn (functional zone) of normal colonic mucosa, whereas the lower portions of the crypts (proliferative compartment) were unreactive with both AE1 and AE3. Polypoid lesions of the colonic mucosa can be placed into two categories based on their patterns of cytokeratin expression. Solitary tubular adenomas and hyperplastic polyps are composed of AE1 and AE3 nonexpressing cells with only few, patchy areas of AE1 and AE3 expressing cells present within glands and in the surface epithelium. In contrast, villous adenomas show strong AE1 and AE3 reactivity throughout the glands. Furthermore, tubular and villous adenomas, and even histologically normal mucosa in patients with familial polyposis, show AE1/AE3 expression throughout the glands and surface epithelium. Colonic carcinomas show a predominance of AE1/AE3 expressing cells. Thus, cytokeratins recognized by monoclonal antibodies AE1 and AE3 represent molecular markers of cellular maturation in the normal colonic mucosa, that are expressed in colonic carcinomas and, in addition, serve as markers that distinguish colonic mucosa and adenomas with a high risk for development of cancers from those with a lower risk.

Topics: Adenocarcinoma; Adenoma; Adenomatous Polyposis Coli; Antibodies, Monoclonal; Cell Differentiation; Cell Transformation, Neoplastic; Colon; Colonic Neoplasms; Epithelium; Humans; Hyperplasia; Intestinal Mucosa; Keratins

The authors present a case of benign oncocytoma (oxyphil cell adenoma) of the nasal cavity in a young woman. This is the fifth case reported in that region. Immunohistochemical stains revealed positivity only for cytokeratin.

Topics: Adenoma; Adult; Female; Humans; Immunohistochemistry; Keratins; Nasal Cavity; Nasal Mucosa; Nose Neoplasms

The intermediate-filament proteins of normal, hyperplastic, and adenomatous parathyroid glands were analyzed immunohistochemically and by immunoblotting with monospecific antibodies. In both normal and adenomatous parathyroid glands, we found keratins with molecular weights of 52, 45, and 40 kilodaltons (Nos. 8, 18, and 19, respectively). Vimentin proteins could be identified only in stromal cells, while glial fibrillary acidic protein was not found. In normal parathyroid glands, neurofilament positivity was seen only in nerve axons. In five of 15 parathyroid gland adenomas some keratin-positive cells expressed neurofilamentlike immunoreactivity also. In cytoskeletal extracts of one adenoma, the 200-kilodalton neurofilament protein was identified by immunoblotting. Thus it appears that some parathyroid gland adenoma cells may acquire neurofilament proteins and coexpress cytokeratin and neurofilament polypeptide in a way comparable with that reported in certain neuroendocrine tumors.

Topics: Adenoma; Antibodies, Monoclonal; Fluorescent Antibody Technique; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Neoplasm Proteins; Parathyroid Glands; Parathyroid Neoplasms; Vimentin

Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.

Topics: Actins; Adenolymphoma; Adenoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Membrane Proteins; Mucin-1; Muscle, Smooth; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Oncocytomas and Warthin's tumors were studied ultrastructurally and with immunofluorescence microscopic techniques against cytokeratins, desmin, vimentin, and actin, the latter characterizing myoepithelial cells. The cell types were found within oncocytomas, one type packed with mitochondria and virtually without filaments, the other contained fewer mitochondria but large amounts of cytokeratins. In Warthin's tumors, all cells contained cytokeratins, the basal cell to a much higher degree. No tumor cells contained vimentin or desmin. Actin was found only close to the apical cell surface in the cylindrical cells in the Warthin's tumors and around the few acinar lumina found in the oncocytomas; thus, a myoepithelial origin of oncocytic tumors of salivary glands seems less plausible. The similarity in staining pattern, namely the pronounced dimorphism of both tumor types, indicates a common progenitor of oncocytomas and the epithelial component in adenolymphomas.

Topics: Actins; Adenolymphoma; Adenoma; Deoxyribonuclease I; Desmin; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Microscopy, Electron; Parotid Neoplasms; Vimentin

Fibrous bodies in growth hormone-secreting adenomas were studied by immunocytochemistry using an anti-cytokeratin antiserum. Fibrous bodies are a feature of acidophil and chromophobe adenomas and are usually associated with acromegaly. Ultrastructural examination revealed round juxtanuclear filamentous aggregates, composed of 8-nm filaments and other organelles. This study demonstrated that the intermediate filaments of fibrous bodies belong to the cytokeratin class. The etiology and significance of these filamentous aggregates remain obscure.

Topics: Adenoma; Cytoskeleton; Female; Growth Hormone; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Organoids; Pituitary Neoplasms

Five thousand seven hundred seventy-eight adenomas or adenomas containing carcinoma from 3215 patients were examined by routine histologic methods for the presence of epithelial metaplasias. Three forms of epithelial metaplasia were encountered: squamous cell metaplasia (0.44%), Paneth cell metaplasia (0.20%), and melanocytic metaplasia (0.017%). In several instances multiple forms of metaplasia were encountered in the same polyp. In those cases in which the paraffin blocks were available, a Grimelius stain was performed. Grimelius-positive cells were present in 63% of the adenomas containing a metaplastic cell type. All cases with Paneth cell differentiation were immunoreactive for lysozyme; all lesions containing areas of squamous differentiation were immunoreactive for keratin except 2. The histopathologic features of these cases are discussed, and it is concluded that rather than representing a true metaplastic process, Paneth cell, squamous cell, and melanocyte differentiation represent the full range of cellular differentiation that endodermally derived tissues can exhibit, particularly when they undergo neoplastic alterations.

Topics: Adenoma; Adult; Age Factors; Aged; Cell Differentiation; Colonic Neoplasms; Female; Histocytochemistry; Humans; Intestinal Polyps; Intestine, Large; Keratins; Male; Melanocytes; Metaplasia; Middle Aged; Muramidase; Rectal Neoplasms; Retrospective Studies; Sex Factors

We performed a comparative study using immunoperoxidase staining on 11 cases of thyroid micro cancer (TCM) and 7 cases of clinically manifested cancers (CMC). Antibodies against 4 kinds of cytoskeletal proteins and thyroglobulin were used. In the TCM and CMC groups, actin and myosin were identified in almost all neoplastic cells of all patients; keratin and vimentin were present in the tumor cells of several patients. Keratin was found only in papillary carcinoma cells. Thyroglobulin was present in the neoplastic cells of several patients from both groups; follicular carcinoma cells and keratin-negative cells reacted more strongly with thyroglobulin than papillary carcinoma cells or keratin-positive cells. There was no special difference between TMC and CMC in the localization of cytoskeletal proteins and thyroglobulin.

Topics: Adenoma; Adult; Aged; Desmin; Female; Glial Fibrillary Acidic Protein; Goiter; Humans; Intermediate Filament Proteins; Keratins; Middle Aged; Neoplasm Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroiditis, Autoimmune; Vimentin

Ten non-neoplastic pituitary glands and 22 pituitary adenomas producing different hormones were studied by immunofluorescence microscopy as well as peroxidase-antiperoxidase and biotin-avidin techniques on frozen sections and formalin-fixed, paraffin-embedded material using antibodies to cytokeratin, vimentin, GFAP, neurofilament protein and different pituitary hormones. The endocrine cells in non-neoplastic pituitary glands as well as in most pituitary adenomas were cytokeratin-positive. The cytoplasmic cytokeratin distribution patterns of non-neoplastic and tumor cells were similar and typical of the type of hormone produced: GH-producing normal cells showed a paranuclear condensation of cytokeratin-reactive intermediate filaments; this accumulation was even further accentuated in GH-producing adenomas resulting in fibrous bodies (Kovacs and Horvath 1978) decorated by cytokeratin antibodies. Prolactin-producing cells showed a less intense cytoplasmic cytokeratin-specific staining with focal paranuclear accentuation in non-neoplastic as well as in neoplastic glands. ACTH-producing cells in normal pituitary glands as well as in adenomas exhibited a strong and more uniform cytoplasmic cytokeratin staining. The cytokeratin reactivity in glycoprotein hormone-producing cells of non-neoplastic tissue and adenomas was weak. Vimentin and GFAP reactivity was confined to agranular folliculo-stellate cells. The specific and different distribution patterns of cytokeratins in pituitary cells can, therefore, provide an (indirect) indication to the production of a specific hormone if immunocytochemistry fails to demonstrate hormone production.

Topics: Adenoma; Female; Histocytochemistry; Humans; Immunochemistry; Intermediate Filament Proteins; Keratins; Male; Microscopy, Fluorescence; Pituitary Gland; Pituitary Neoplasms; Tissue Distribution

Topics: Adenoma; Fluorescent Antibody Technique; Histocytochemistry; Humans; Keratins; Microscopy, Electron; Muscle Proteins; Parotid Neoplasms; Vimentin

Fifteen adenomatoid tumors were examined immunohistochemically using antibody probes to keratin and factor VIII-related antigen. Cells lining adenoid structures labeled using keratin antibody in all 15 tumors but failed to label with factor VIII-related antigen antibodies in any case. In one case tissue was retrieved from a paraffin block and studied by immunoelectron microscopy using the two antibody probes. Immunoprecipitate was demonstrated in adenoid cells adjacent to desmosomes using keratin antibody but was absent using factor VIII-related antigen antibodies. Of the two prevailing theories of origin for adenomatoid tumors, based on ultrastructural and histochemical data to date, these results are additional evidence for a mesothelial origin and fail to support an endothelial origin.

Topics: Adenoma; Adult; Antibodies; Enzyme-Linked Immunosorbent Assay; Factor VIII; Female; Horseradish Peroxidase; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged

The distribution of intermediate - sized filaments in human colon mucosa as well as in adenomas and carcinomas of the colon was studied by means of both immunohistology and electron microscopy. The epithelial cells of the colonic mucosa are definitely labelled with antibodies against prekeratin (cytokeratin). Interwoven filaments of the prekeratin type are present in the basal compartments of the epithelial cells; they surround the nuclei and mucus droplets and form an apical skeletal disc. Pericryptal connective tissue is prekeratin negative and vimentin positive. Benign hyperplastic polyps have a high content of prekeratin. The potential precursors of colonic carcinoma, i.e., the tubular and villous adenomas, also show an increase in intermediate-sized filaments of the prekeratin type. Correspondingly, electron microscopy reveals elongated bundles of intermediate-sized filaments arising from the desmosomes of the lateral and basal cell membranes. The prekeratin content is particularly high in adenocarcinomas and highest in mucinous carcinomas. As expected, the stroma of all neoplasms studied is prekeratin-negative, but distinctly vimentin-positive. In one moderately differentiated adenocarcinoma there was evidence of "vimentin-positive" tumor cells. These changes may be caused by binding of cytokeratins with an unknown substance in vimentin antisera, as observed similarly by Moll et al. (1982) in a transitional cloacogenic carcinoma.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenoma; Colon; Colonic Neoplasms; Cytoskeleton; Humans; Intermediate Filament Proteins; Intestinal Mucosa; Keratins; Microscopy, Electron; Protein Precursors; Vimentin

Antibodies against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used.

Topics: Adenoma; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Parakeratosis; Salivary Gland Neoplasms; Salivary Glands; Skin; Skin Neoplasms; Thymus Gland; Thymus Neoplasms

The intermediate-sized filaments can be divided into several groups which are characteristic of different types of tissues (e.g.: epithelial, mesenchymal, muscle, astrocytic and neural origin). Antibodies specific for some of these filament types have been used to analyse a group of salivary gland tumours. Prekeratin-positive cells were seen in the normal gland, cystadenolymphomas, mucoepidermoid tumours, and squamous cell carcinomas which are all tumours of epithelial origin. The pleomorphic adenomas showed the presence of some cells which appeared to contain both prekeratin and vimentin. The results are discussed with respect to their histogenetic implications.

Topics: Adenoma; Carcinoma; Carcinoma, Squamous Cell; Cytoskeleton; Desmin; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Protein Precursors; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

Topics: Adenoma; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cytoskeleton; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Parotid Neoplasms; Salivary Gland Neoplasms

The aim of this study was to analyze the filament distribution in the parotid gland and their tumors. A correlation to the histogenetic implications and histological properties was attempted. Normal rat and human parotid glands as well as pleomorphic adenomas and squamous cell carcinomas of this gland were examined by the indirect immunoperoxidase technique using antibodies to the keratin polypeptide of 67,000 dalton, and 55,000 dalton and anti-actin auto-antibodies. Both keratin and actin antigens were demonstrated in the duct system and in the myoepithelial cells of the normal salivary glands. The acinar cells remained negative. In pleomorphic adenomas, there were numerous keratin-positive spindle-shaped cells which represented the so-called myoepithelial cells. These cells were demonstrated to contain actin, too. The tubular duct-like structures were labeled by keratin antiserum and by anti-actin auto-antibodies. In squamous cell carcinomas, the majority of the tumor cells were strongly labeled by keratin antibodies. Actin was detected in these malignant cells, too. Our results show important differences in the cellular elements of the normal salivary glands with regard to their filament distribution. In normal and tumoral conditions, our findings support the hypothesis of the epithelial nature of the myoepithelial cells. Our preliminary results encourage the research of filamentous structures for scientific and diagnostic purposes.

Topics: Actins; Adenoma; Animals; Carcinoma, Squamous Cell; Cytoskeleton; Histocytochemistry; Keratins; Male; Parotid Gland; Parotid Neoplasms; Rats

To identify keratin, the immunoperoxidase technique was performed on 41 nontumourous pituitaries, 14 pituitary adenomas composed of different cell types and 15 craniopharyngiomas. No keratin was demonstrated in adenohypophysial cells, neurohypophysis or hypophysial vessels, however, it was occasionally identified in the pairs intermedia within cells lining cystic structures. Crooke's hyaline material and all pituitary adenomas were negative for keratin. The epithelial portions of craniopharyngiomas exhibited positive keratin immunostaining, as did squamous cell nests, which are frequently found in hypophysial stalk. Immunostaining for keratin can effectively be used in the differential diagnosis of pituitary tumours and may prove valuable in the investigation of histogenesis and embryology.

Topics: Adenoma; Craniopharyngioma; Humans; Immunoenzyme Techniques; Keratins; Pituitary Neoplasms

Six of 70 female Sprague-Dawley rats given a single intravenous injection of 7,12-dimethylbenz[a]anthracene (DMBA) developed 7 pilosebaceous tumors. Two of the tumors showed differentiation toward the upper portion of the pilosebaceous unit while 5 showed differentiation toward the lower portion. Each tumor was examined histochemically for the presence of inner root sheath keratin of the hair follicle using the carbamido diacetyl reaction for citrulline and for hair shaft keratin using boiling ninhydrin reagent. The 2 tumors of the upper portion of the pilosebaceous unit were sebaceous adenomas which were accompained by a keratinizing epithelim like that of the sebaceous gland duct and upper pilosebaceous canal. Histochemically, the keratin was not like that of hair shaft nor inner root sheath. The 5 tumors showing differentiation toward components of the lower pilosebaceous unit were trichoepitheliomas. They were composed of structures which, to varying degrees, recapitulated the organization of the normal hair follicle. Within these follicular structures, both inner root sheath and hair shaft type keratins were found. The occurrence of skin tumors after the intravenous administration of DMBA was unexpected since it is uncommon for skin tumors to be produced by the systematic administration of chemical carcinogens and they have never been described after the oral administration of DMBA. That the route of administration may influence tumor production with this carcinogen is suggested by the fact that the only other reported tumors, which were squamous carcinomas, also followed intravenous injection of DMBA.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenoma; Animals; Benz(a)Anthracenes; Female; Hair; Injections, Intravenous; Keratins; Neoplasms, Experimental; Rats; Sebaceous Gland Neoplasms; Skin Neoplasms

Topics: Adenoma; Breast; Breast Neoplasms; Epidermal Cyst; Humans; Keratins; Medical Records; Metaplasia