bromochloroacetic-acid and Pituitary-Neoplasms

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

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

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

To analyze the co-expression of the intermediate filaments GFAP and cytokeratin in 326 pituitary adenomas with regard to the distribution pattern, the subtype of the adenoma and clinical prognostic data.. Tissue from 326 pituitary adenomas and 13 normal anterior pituitaries collected in the Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, between 2006 and 2009 was investigated by immunohistochemistry, immunofluorescence and electron microscopy.. Co-expression of intermediate filaments GFAP and cytokeratin was associated with hormone expression in 62/278 cases (22%), but only found in 2/48 (4%) of null cell adenomas (p < 0.01). Simultaneous co-expression of GFAP and cytokeratin in the same cells was demonstrated in 26 out of 326 pituitary adenomas and in all 13 pituitaries. In pituitary intermediate filaments were demonstrated in a larger area of the cytoplasm than in adenoma (p < 0.01), however, overlapping expression was seen in 2.6% of the total area in both, pituitary and adenoma. Congenially, cells with overlapping expression were found near vessels and in follicles. Furthermore, adenomas with cellular co-expression of GFAP and cytokeratin were associated with a lower recurrence rate (7.7%) compared to adenomas without co-expression of intermediate filaments (17.8%).. Cellular co-expression of the intermediate filaments GFAP and cytokeratin in pituitary adenomas and the pituitary was demonstrated and shown to be associated with hormone expression and low recurrence rate. The results are discussed with regard to the biology of folliculostellate cells, neural transformation and tumor stem cells. This study may complement the understanding of pituitary adenoma biology.

Topics: Female; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Middle Aged; Pituitary Neoplasms

The presence and patterns of keratins are critical in the classification of pituitary neuroendocrine tumors. A large body of literature has included information about the staining patterns of pituitary tumors and tissues with the CAM 5.2 antibody. During an antibody validation for clinical use, we carried out staining of a series of 29 surgically resected pituitary cases containing 31 pituitary neuroendocrine tumors that were tested for CAM 5.2 as well as for cytokeratin (CK) 7, 18, 19, and 20 and the pan-keratin cocktail AE1/AE3. The results showed an almost identical staining pattern for CK18 and CAM 5.2; however, CAM 5.2 yielded more intense staining, whereas CK18 provided more delicate results. Staining results using AE1/AE3 were satisfactory but generally less intense; however, this marker was more specific, identifying keratin expression in one tumor that was negative with CAM 5.2. CK19 is expressed in nontumorous adenohypophysis but was less frequently positive in tumors; somatotroph and corticotroph tumors were negative for CK19, but CK19 antibody highlighted follicular cells in some gonadotroph tumors. CK7 and CK20 were negative in all pituitary tissues tested. Our findings underscore the role for CAM 5.2 and CK18 as the most valuable to identify specific alterations in adenohypophysial cells and their tumors; there is also a role for AE1/AE3 to verify the epithelial nature of pituitary neuroendocrine tumors that are negative for CAM 5.2 and CK18.

Topics: Biomarkers, Tumor; Humans; Keratins; Neuroendocrine Tumors; Pituitary Neoplasms

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Topics: beta Catenin; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Cell Differentiation; Craniopharyngioma; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Odontogenesis; Pilomatrixoma; 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

The occurrence of ganglion cells in the sella turcica, in association or not with a pituitary adenoma, has been rarely reported. Various names have been employed for this rare entity, gangliocytoma being frequently used and recommended by WHO classification. Expression of cytokeratin in these ganglion cells has been previously occasionally reported, a very intriguing observation raising questions on the possible nature and derivation of these cells. We describe the pathological findings in three cases of growth hormone-producing adenomas, all sparsely granulated, showing the presence of a ganglion cell population admixed with an adenomatous component. A review of the literature is also provided.

Topics: Adult; Aged; Female; Ganglioneuroma; Humans; Immunohistochemistry; Keratins; Middle Aged; Neurons; Pituitary Neoplasms

Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis.. Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types. The two groups were then compared with regards to proliferation (Ki-67, p53 indexes and mitotic count), differentiation (expression of somatostatin receptors SSTR. The silent somatotroph tumours are not uncommon. Their pathological diagnosis requires the immunodetection of GH and Pit-1. They are more frequently plurihormonal and more proliferative than those with acromegaly. A low secretory activity of these tumours might explain the normal plasma values for GH and insulin-like growth factor 1 (IGF1) and the absence of clinical signs of acromegaly.

Topics: Acromegaly; Adult; Female; Growth Hormone; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Keratins; Male; Middle Aged; Pituitary Neoplasms; Receptors, Somatostatin; Somatomedins; Somatotrophs; Thyrotropin; Transcription Factor Pit-1

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

Metastatic pituitary carcinoma to bone is rare. In this report, we present a case of a 59-year-old female with recurrent pituitary adenoma of the sparsely granulated somatotroph subtype with metastasis to a few bony sites 10 years later. Needle core biopsy (NCB) with touch preparations was performed on a 5 mm lesion in left ilium. Diff-Quik stained NCB touch preparation slides showed a few loosely cohesive epithelial polygonal cells that were arranged in nests or acini, or singly, had scant vacuolated cytoplasm and eccentrically located round nuclei (plasmacytoid) with slight nuclear pleomorphism, fine granular chromatin, conspicuous nucleoli, and smooth nuclear membrane. Trilineage hematopoietic cells of bone marrow were also appreciated in the background. H&E stained core sections showed fragments of bone and bone marrow with nests of bland epithelial cells with similar cytomorphology as seen in NCB touch preparation slides. The tumor cells were immunoreactive for juxtanuclear dot-like staining of pan-cytokeratin (CAM 5.2 and AE1/AE3) (a specific feature), neuroendocrine markers (CD56, synaptophysin, and chromogranin. Additionally, scattered cells were immunoreactive for growth hormone. Molecular test showed that tumor cells were negative for the promoter methylation of O-6-Methylguanine-DNA Methyltransferase (MGMT). Final diagnosis of metastatic pituitary carcinoma was rendered. Morphology of metastatic pituitary carcinoma, its differential, clinical presentation and treatment were discussed. Diagn. Cytopathol. 2017;45:645-650. © 2017 Wiley Periodicals, Inc.

Topics: Adenocarcinoma; Anion Exchange Protein 1, Erythrocyte; Biomarkers; Biomarkers, Tumor; Biopsy, Large-Core Needle; Bone Neoplasms; CD56 Antigen; Chromogranin A; Female; Gene Expression; Growth Hormone; Humans; Ilium; Keratins; Middle Aged; Pituitary Neoplasms; Synaptophysin

Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor are the main entities presenting ghost cells as an important histological feature, in spite their quite different clinical presentation; it seems that they share a common pathway in the formation of these cells. The aim of this study is to examine and compare the characteristics of ghost and other cells that form these lesions.. Forty-three cases including 21 pilomatrixomas, 14 craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated by immunohistochemistry for cytokeratins, CD138, β-catenin, D2-40, Glut-1, FAS, CD10 and also by scanning electron microscopy.. The CKs, CD138, β-catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of craniopharyngioma and calcifying cystic odontogenic tumor, compared with pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138 and CD10. Differences on expression pattern were identified in transitional and basal cells, as ghost cells were negative for most antibodies used, except by low expression for cytokeratins. By scanning electron microscopy, the morphology of ghost cells were similar in their fibrillar cytoplasm, but their pattern varied from sheets in pilomatrixoma to small clusters in craniopharyngioma and calcifying cystic odontogenic tumor.. Mechanisms involved in formation of ghost cells are unknown, but probably they follow different pathways as protein expression in the basal/transitional cells was not uniform in the three tumors studied.

Topics: beta Catenin; Craniopharyngioma; Epithelial Cells; fas Receptor; Glucose Transporter Type 1; Hair Diseases; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Microscopy, Electron, Scanning; Neprilysin; Odontogenic Cyst, Calcifying; Odontogenic Tumors; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms; Syndecan-1

Patients with germline AIP mutations or low AIP protein expression have large, invasive somatotroph adenomas and poor response to somatostatin analogues (SSA).. To study the mechanism of low AIP protein expression 31 sporadic somatotropinomas with low (n = 13) or high (n = 18) AIP protein expression were analyzed for expression of AIP messenger RNA (mRNA) and 11 microRNAs (miRNAs) predicted to bind the 3'UTR of AIP. Luciferase reporter assays of wild-type and deletion constructs of AIP-3'UTR were used to study the effect of the selected miRNAs in GH3 cells. Endogenous AIP protein and mRNA levels were measured after miRNA over- and underexpression in HEK293 and GH3 cells.. No significant difference was observed in AIP mRNA expression between tumors with low or high AIP protein expression suggesting post-transcriptional regulation. miR-34a was highly expressed in low AIP protein samples compared high AIP protein adenomas and miR-34a levels were inversely correlated with response to SSA therapy. miR-34a inhibited the luciferase-AIP-3'UTR construct, suggesting that miR-34a binds to AIP-3'UTR. Deletion mutants of the 3 different predicted binding sites in AIP-3'UTR identified the c.*6-30 site to be involved in miR-34a's activity. miR-34a overexpression in HEK293 and GH3 cells resulted in inhibition of endogenous AIP protein expression.. Low AIP protein expression is associated with high miR-34a expression. miR-34a can down-regulate AIP-protein but not RNA expression in vitro. miR-34a is a negative regulator of AIP-protein expression and could be responsible for the low AIP expression observed in somatotropinomas with an invasive phenotype and resistance to SSA.

Topics: Adult; Animals; Base Sequence; Binding Sites; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Growth Hormone-Secreting Pituitary Adenoma; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins; Keratins; Male; MicroRNAs; Middle Aged; Neoplasm Invasiveness; Pituitary Neoplasms; Rats; RNA, Messenger; Sequence Alignment

Topics: Actins; Carcinosarcoma; Craniopharyngioma; Diagnosis, Differential; Esthesioneuroblastoma, Olfactory; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Nasal Cavity; Nose Neoplasms; Paranasal Sinus Neoplasms; Pituitary Neoplasms; Teratoma; Vimentin

Only one study has evaluated Ki-67 as a predictor of the response to somatostatin analog therapy in acromegaly; however, other predictors like somatostatin receptor type 2 (SSTR2) and cytokeratin pattern expressions were not considered.. To evaluate whether Ki-67 is a predictor of octreotide LAR (OCT-LAR) response in somatotropinomas independent of SSTR2 and cytokeratin expression patterns.. Protein expression was analyzed by immunohistochemistry. The percentage of cell nuclei that were immunolabeled for Ki-67 and the percentage of cells with positive SSTR2 staining were calculated. SSTR2 expression was considered high when ≥25%, and a cutoff of 2.3% was designated for Ki-67. Tumors were classified as densely or sparsely granulated according to the cytokeratin pattern.. Thirty-one somatotropinomas were studied. Fourteen patients (45.2%) were controlled with OCT-LAR therapy. The median Ki-67 labeling index (LI) was higher in patients not controlled with OCT-LAR than in those controlled (1.63 and 0.15 respectively, P=0.002). Higher SSTR2 expression and densely granulated tumors were correlated with control as well (P=0.04 and 0.038 respectively). There was no difference in Ki-67 levels between patients with high and low SSTR2 expression (P=0.651). After multivariate analysis, both Ki-67 and SSTR2 remained statistically significant as predictors of OCT-LAR response (P=0.017 and 0.012 respectively). The Ki-67 LI was higher in sparsely than in densely granulated tumors (P=0.047).. Ki-67 is a predictor of response to OCT-LAR in acromegaly, independent of SSTR2 expression and relates to cytokeratin patterns.

Topics: Acromegaly; Adult; Antineoplastic Agents, Hormonal; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Logistic Models; Middle Aged; Multivariate Analysis; Octreotide; Pituitary Neoplasms; Receptors, Somatostatin; Young Adult

Rathke's cleft cyst (RCC) with significant squamous and/or stratified epithelium including smooth transition from single cuboidal to squamous epithelium (tRCC) is rare and possibly represents an intermediate form to craniopharyngioma.. Twelve patients with histologically confirmed tRCC were retrospectively investigated from a series of 167 cases of RCC and 96 cases of craniopharyngiomas. Clinical data were reviewed, and immunohistochemistry findings for cytokeratins and β-catenin were examined.. All lesions were located in the sella turcica with marked extension to suprasellar cistern. Six of the 12 patients had suffered postoperative re-enlargement, and three of these six patients required more than two additional operations and irradiation. CAM5.2 was positive in the glandular epithelium in all tRCCs and focally positive in the squamous epithelium of all these tRCCs. 34βE12 was positive in the squamous epithelium in all tRCCs and focally positive in the glandular epithelium in all but one tRCC. The findings of cytokeratin expression of tRCCs were very similar to those of craniopharyngioma. β-Catenin showed nuclear translocation in five cases. All patients with nuclear translocation of β-catenin suffered postoperative re-enlargement.. tRCC carries an extremely high risk of re-enlargement. Cytokeratin expression resembles that in craniopharyngioma, which might indicate a very close origin of these pathologies. Nuclear translocation of β-catenin may be related to the aggressive clinical course.

Topics: Adolescent; Adult; Aged; beta Catenin; Central Nervous System Cysts; Child; Craniopharyngioma; Female; Humans; Keratins; Male; Metaplasia; Middle Aged; Pituitary Neoplasms; Postoperative Period; Retrospective Studies; Risk Factors; Young Adult

Podoplanin, a transmembrane sialomucin-like glycoprotein, is a specific marker of lymphatic vessels, and its expression is also considered to be associated with tumor invasion and tooth development. In this study, we examined the expression of podoplanin in calcifying cystic odontogenic tumor (CCOT) in comparison with that in other so-called hard α-keratin-expressing tumors such as craniopharyngioma (CP) and pilomatrixoma (PM). Immunohistochemical staining for podoplanin was carried out using surgical specimens of 15 CCOTs of the jaw, 19 CPs of the pituitary gland, and 15 PMs of the skin. Positivity for hard α-keratin was evident in ghost, shadow and transitional cells in all of these tumors (100%). The podoplanin expression in CCOTs was evident in the periphery of ameloblastoma-like epithelium (86.6%) and the epithelial cells adjacent to ghost cells (60%). On the other hand, in adamantinomatous-type CPs, podoplanin expression was observed in epithelial components corresponding to the stratum intermedium (100%), but not in the periphery of ameloblastoma-like epithelium (0%). In squamous-type CPs podoplanin was expressed in basal cells (100%), but all of the PMs were podoplanin-negative (0%). In the periphery of the ameloblastoma-like epithelium or basophilic cell layer, podoplanin was expressed more strongly in CCOTs than in CPs or PMs. These findings suggest that the expression of podoplanin in CCOTs may reflect rapid turnover of cytoskeletal filaments and local invasiveness.

Topics: Basophils; Biomarkers, Tumor; Craniopharyngioma; Cytoskeleton; Epithelial Cells; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Membrane Glycoproteins; Neoplasm Invasiveness; Odontogenic Tumors; Odontoma; Pilomatrixoma; Pituitary Neoplasms; Skin 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

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

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

Ghost cell odontogenic carcinoma (GCOC) is the malignant counterpart of calcifying cystic odontogenic tumour and dentinogenic ghost cell tumour. This is the case of a middle-aged male who presented with a slow-growing maxillary tumour. He was asymptomatic until pain symptoms developed prior to initial presentation. The excised tumour was diagnosed as a ghost cell odontogenic carcinoma. More case reports are needed for further understanding of this rare malignant odontogenic tumour.

Topics: Adult; Biopsy; Craniopharyngioma; Diagnosis, Differential; Humans; Keratins; Male; Maxillary Neoplasms; Maxillary Sinusitis; Odontogenic Tumors; Pituitary Neoplasms; Radiography, Panoramic; Tomography, X-Ray Computed

Pituitary adenoma is a rare neoplasm in childhood, with prolactin and adrenocorticotropic hormone (ACTH)-secreting adenomas predominating in this age group. Herein is reported a case of an ACTH-producing macroadenoma with an unusual histology that occurred in a 2-year-old girl. Because of the patient's age and the macroadenoma's suprasellar location and large size (up to 4 cm in diameter), radical surgery was performed under the suspicion of craniopharyngioma or germ-cell tumor. Pathologically, it was a unique pituitary adenoma composed of monotonous ACTH-producing cells, smaller folliculo-stellate cells (FSC), and mucin-producing cells. The FSC, non-hormone-secreting pituitary cells of uncertain function, were confirmed by their S-100 protein, glial fibrillary acidic protein and cytokeratin expression immunoprofiles. The abrupt transition between the prominent gland-forming mucin-producing epithelia and the FSC component suggested that the mucin-producing epithelia might be derived from the FSC. This association might represent so-called 'retrodifferentiation' of adenoma cells to the FSC and the precursor cells of Rathke's pouch.

Topics: ACTH-Secreting Pituitary Adenoma; Biomarkers, Tumor; Child, Preschool; Cytoplasm; Disease Progression; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Magnetic Resonance Imaging; Mucins; Pituitary Neoplasms; S100 Proteins; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adrenocorticotropic Hormone; Biomarkers; Homeodomain Proteins; Human Growth Hormone; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Microscopy, Electron; Pituitary Neoplasms; Prolactin; Receptors, Cytoplasmic and Nuclear; Steroidogenic Factor 1; Thyrotropin; Transcription Factor Pit-1; Transcription Factors; Tumor Suppressor Protein p53; World Health Organization

Topics: Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Microscopy, Electron; Mitotic Index; Neoplasm Invasiveness; Nucleic Acid Hybridization; Pituitary Neoplasms; Prognosis; Proto-Oncogene Proteins; Thyrotropin; World Health Organization

To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard alpha-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard alpha-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst. In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components. Immunoreactivity for phosphothreonine, detected in hard alpha-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors.

Topics: Animals; Biomarkers, Tumor; Blotting, Western; Cells, Cultured; Craniopharyngioma; Hair; Hair Diseases; Humans; Hybridomas; Immunoenzyme Techniques; Jaw Neoplasms; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Neoplasms; Odontogenic Cyst, Calcifying; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms

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

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

Craniopharyngiomas are epithelial neoplasms usually located in the sellar and suprasellar regions. Distinguishing craniopharyngioma from Rathke cleft cyst is sometimes difficult, and the distinction is clinically significant because Rathke cleft cysts have a better prognosis than craniopharyngiomas.. We retrieved 10 cases with a primary diagnosis of craniopharyngioma and 5 cases with a diagnosis of Rathke cleft cyst for analysis. Five cases of normal pars intermedia of pituitary glands from autopsy served as controls. We evaluated the expression patterns of a broad range of low- to intermediate-molecular weight cytokeratins (CK7, CK8, CK10, CK17, CK18, CK19, and CK20) and high-molecular weight cytokeratins (K903: a combination of CK1, CK5, CK10, and CK14; and CK5/6) in these cases.. Craniopharyngiomas had a cytokeratin expression pattern distinct from that of Rathke cleft cysts and pituitary gland pars intermedia: craniopharyngiomas did not express cytokeratins 8 and 20, whereas Rathke cleft cysts and pars intermedia of pituitary glands both expressed cytokeratins 8 and 20.. The differential expression of cytokeratins distinguishes between craniopharyngioma and Rathke cleft cyst, and this difference could be useful for identifying craniopharyngioma in difficult cases in which only a small biopsy is available. The different cytokeratin profiles of craniopharyngioma and Rathke cleft cyst suggest that these lesions do not come from the same origin, or that they come from a different developmental stage of the pouch epithelium.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Cell Count; Central Nervous System Cysts; Child; Child, Preschool; Craniopharyngioma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Molecular Weight; Pituitary Neoplasms

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

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

Craniopharyngiomas are generally considered to arise from the remnants of Rathke's pouch or a misplaced enamel organ. We tried to refine these hypotheses, comparing the subtypes of craniopharyngioma with Rathke's cleft cyst, a known Rathke's pouch derivative, and with ameloblastoma, an enamel organ derivative. Nineteen craniopharyngiomas (14 adamantinomatous and 5 papillary type tumors) and 17 ameloblastomas were immunostained for cytokeratin (CK) 7, CK 8, CK 14, and human hair keratin (HHK). All cases of adamantinomatous craniopharyngioma were CK 7+/CK 8+/CK 14+. Two cases (40%) of papillary craniopharyngioma were CK 7+/CK 8+/CK 14+, whereas the remaining three cases (60%) were CK 7+/CK 8-/CK 14+. Fifteen cases (88%) of ameloblastoma were CK 7-/CK 8+/CK 14+. Only the shadow cells present in adamantinomatous craniopharyngiomas were positive for HHK, which may indicate their follicular differentiation. In Rathke's cleft cyst, ciliated cuboidal cells were CK 7+/CK 8+/CK 14- and metaplastic squamous cells were CK 7+/CK 8/CK 14+. These findings suggest that both subtypes of craniopharyngioma may differ from ameloblastoma in histogenesis, although cytokeratin expression patterns may change during tumor development. Adamantinomatous craniopharyngioma may be related to a heterotopic ectodermal tissue which can differentiate into hair follicles, while papillary craniopharyngioma may arise from Rathke's cleft cyst.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ameloblastoma; Biomarkers, Tumor; Craniopharyngioma; Female; Humans; Immunoenzyme Techniques; Jaw Neoplasms; Keratins; Male; Middle Aged; Neoplasm Proteins; Pituitary Neoplasms; Retrospective Studies

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

The monoclonal antibody NCL-CK13 was studied in specimens of craniopharyngioma, ameloblastoma and calcifying odontogenic cyst neoplasms and the mandible and maxillae of normal human fetuses. There was a decrease in NCL-CK13 as the dental lamina developed, with a complete loss in the enamel organ. The neoplastic epithelia of the neoplasms revealed a clear phenotypic and immunohistochemical reactive relationship to the stratified embroyonic mucosa, away from the enamel organ. This suggests that these neoplasms might have their histogenesis from early stage epithelium, the oral part of the dental lamina or its remnants.

Topics: Ameloblastoma; Amelogenesis; Case-Control Studies; Craniopharyngioma; Dental Enamel; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Odontogenesis; Odontogenic Cyst, Calcifying; Phenotype; Pituitary Neoplasms

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

Topics: Animals; Brain Neoplasms; Carcinoma, Squamous Cell; Cattle; Cattle Diseases; Diagnosis, Differential; Euthanasia; Eyelid Neoplasms; Female; Horner Syndrome; Keratins; Pituitary Gland; Pituitary Neoplasms; Vimentin

The objective of this investigation was to study the relationship of the ghost cell ameloblastoma (GCA), which is a form of type II calcifying odontogenic cyst (COC), to the adamantinomatous craniopharyngioma (ACP). H&E sections of 26 examples of ACP were compared to three cases of GCA and to the reported microscopic features of that tumor. Clinical records of the ACPs were studied to determine their biologic behavior compared to that of the ameloblastomas. Immunohistochemical studies of nine examples of ACP were performed for KL1 (high mol.wt cytokeratins), 5D3 (low mol.wt cytokeratins) and involucrin (characteristic of terminally differentiated keratinocytes) using the peroxidase-antiperoxidase method. The results were compared with those reported for COC and ameloblastoma. ACP and GCA exhibited similar microscopic features, including pre-ameloblasts, tissue resembling stellate reticulum, ghost cells and calcifications; both tumors grew slowly and were invasive. ACP and COC, and by interpolation GCA, exhibited similar features with all three antibodies. The ghost cells did not exhibit any immunoreactivity but the adjacent cells stained positively for involucrin. The immunological features of ACP were similar to those reported in ameloblastomas for squamous differentiation. However, because of their rarity, no ameloblastomas exhibiting keratinization, including ghost cells, have yet been studied with these antibodies. We conclude that ACP and GCA are homologous lesions.

Topics: Ameloblastoma; Ameloblasts; Biology; Calcinosis; Cell Differentiation; Coloring Agents; Craniopharyngioma; Eosine Yellowish-(YS); Epithelial Cells; Fluorescent Dyes; Hematoxylin; Humans; Immunoenzyme Techniques; Immunohistochemistry; Jaw Neoplasms; Keratinocytes; Keratins; Molecular Weight; Odontogenic Cyst, Calcifying; Pituitary Neoplasms; Protein Precursors

Topics: Adult; Cerebral Ventricles; Cerebral Ventriculography; Cholesterol; Dermoid Cyst; Humans; Keratins; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Rupture, Spontaneous; Tomography, X-Ray Computed

To identify the CT and MR characteristics of craniopharyngiomas, to evaluate the histologic types of craniopharyngioma, and to compare the radiologic/histologic appearance and type of therapy with tumor recurrence.. We reviewed the records of 45 patients with craniopharyngiomas for which surgical specimens (n = 45), preoperative MR or CT studies (n = 27), or other MR or CT studies or reports (n = 18) were available. Radiologic appearance, histologic morphology, treatment, and tumor recurrence were studied.. Adamantinomatous epithelium was found in 40 of 45 surgical specimens, keratin in 34 of 45, and squamous epithelium in 11 of 45. A continuum of mixed morphology rather than distinct subtypes of tumors was found. The radiologic appearance did not correlate with the histologic features. No statistically significant difference was found between children and adults with respect to tumor size, calcification, histology, or tumor recurrence. Patients treated with radiation after subtotal resection had far fewer tumor recurrences (n = 3) than patients treated with surgery alone (n = 18).. Craniopharyngiomas could not be divided into distinct histologic types. No differentiating radiologic or histologic characteristics could be established for craniopharyngiomas in children versus adults. Radiation treatment was strongly associated with tumor regression or lack of recurrence.

Topics: Adolescent; Adult; Age Factors; Calcinosis; Child; Child, Preschool; Craniopharyngioma; Epithelium; Female; Follow-Up Studies; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Radiotherapy, Adjuvant; Remission Induction; Retrospective Studies; Tomography, X-Ray Computed

The histogenesis of craniopharyngiomas was immunohistochemically studied on the basis of cytokeratins (CK) expression, with special reference to histological subtype, i.e., the squamous type (Sq) and adamantinomatous type (Ad). Alcian-Blue staining and immunohistochemical expression of secretory component were also studied to assess secretory activity. Although combined expression of simple-, stratified-, and skin-type CK was detected in both Sq and Ad, the pattern of expression in Sq and Ad was different. Sq displayed epidermal differentiation of CK, and secretory activity was limited to the apical cells of Sq. Based on these findings, the histogenesis of Sq appeared to be from Rathke's pouch, but that of Ad remained obscure.

Topics: Adolescent; Adult; Cell Differentiation; Child; Craniopharyngioma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pituitary Neoplasms

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

Pathological specimens of 131 surgically removed craniopharyngiomas were obtained from the registry of the National Institute of Neurosurgery, Budapest between 1977 and 1991. The cases were reviewed statistically with reference to their gross and microscopic features and clinical characteristics. Macroscopically, 34% of the tumours were cystic, 23% solid and 43% mixed. Histologically, 38% of the cases belonged to the adamantinous group, 26% were squamous epithelial type, 15% were combined, that is expressing the characteristics of both. In 21% of the cases the surgically removed samples did not contain enough material for correct histopathologic classification. There was no recurrence in the group with the squamous epithelial type tumours, while 59% of the adamantinous, and 36% of the combined craniopharyngiomas recurred. The 5-year survival proportion was 73% at the squamous epithelial, 60% in the adamantinous, and 55% at the combined histological types.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Biopsy; Child; Craniopharyngioma; Female; Humans; Hypophysectomy; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Pituitary Gland; Pituitary Neoplasms; Survival Rate; Vimentin

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

A variety of epithelial cysts in the central nervous system were examined immunohistochemically for expression of cytokeratins. Colloid cysts, Rathke's cleft cysts and epithelial cysts in the spinal canal expressed complex type cytokeratins, while enterogenous cysts and neuroectodermal cysts showed only simple type cytokeratins. Colloid cysts showed a pattern of cytokeratins similar to that of upper respiratory tract which is endodermal in origin. In contrast, Rathke's cleft cysts showed a pattern of cytokeratins similar to that of the adenohypophysis and salivary gland which are ectodermal in origin. The CK immunohistochemical studies are discussed with regards to diagnostic significance and origins of their cysts.

Topics: Adult; Central Nervous System Diseases; Cerebral Ventricles; Child, Preschool; Cranial Fossa, Posterior; Craniopharyngioma; Cysts; Fetal Diseases; Humans; Immunohistochemistry; Keratins; Pituitary Neoplasms; Reference Values; Sella Turcica; Spinal Canal

The purpose of this study is to present the histological characteristics of tumor origin and proliferative characteristics of craniopharyngioma. In 25 craniopharyngiomas, the immunoperoxidase technique revealed strong positive reactions for keratin and cytokeratin in cytoplasm of tumor cells. But, immunostaining of keratin and cytokeratin differ from each of layer of craniopharyngioma. The ciliated epithelium in the craniopharyngioma was not stained by keratin, but ciliated epithelium of Rathke's cleft cyst was stained by cytokeratin.

Topics: Antigens, Neoplasm; Craniopharyngioma; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Nuclear Proteins; Pituitary Neoplasms; Proliferating Cell Nuclear Antigen

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

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

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

Twenty one cases of epithelial cysts in the central nervous system including six colloid cysts of the third ventricle, eight Rathke's cleft cysts in the sella, two enterogenous cysts in the posterior fossa, two epithelial cysts in the spinal canal and three neuroectodermal cysts in the cerebrum were examined immunohistochemically for expression of intermediate filamentous proteins-simple type, stratified type and skin type cytokeratins and GFAP. Colloid cysts of the third ventricle. Rathke's cleft cysts in the sella and epithelial cysts in the spinal canal expressed complexed type cytokeratins while enterogenous cysts and neuroectodermal cysts showed only simple type cytokeratins. In addition, several Rathke's cleft cysts demonstrated skin type differentiation and expressed GFAP in occasional lining cells. The characteristic composition and distribution of cytokeratins in various kinds of epithelial cysts in the central nervous system are demonstrated and discussed with regards to their origins.

Topics: Adult; Aged; Aged, 80 and over; Central Nervous System Diseases; Child, Preschool; Craniopharyngioma; Cysts; Epithelium; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pituitary Neoplasms

Nineteen epithelial cysts in the central nervous system including six colloid cysts of the third ventricle, seven Rathke's cleft cysts in the sella, two enterogenous cysts in the posterior fossa, two epithelial cysts in the spinal canal and two neuroectodermal cysts in the cerebrum were examined immunohistochemically for expression of intermediate filament proteins-simple type, stratified type and skin type cytokeratins and GFAP. Colloid cysts of the third ventricle, Rathke's cleft cysts in the sella and epithelial cysts in the spinal canal expressed complex type cytokeratins while enterogenous cysts and neuro-ectodermal cysts showed only simple type cytokeratins. In addition, Rathke's cleft cysts expressed GFAP in occasional lining cells. The characteristic composition and distribution of cytokeratins in various kinds of epithelial cysts in the central nervous system are demonstrated and discussed with regard to their origins.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Choroid Plexus; Craniopharyngioma; Cysts; Ependyma; Epithelium; Female; Humans; Keratins; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Spinal Diseases; Spinal Neoplasms; Spine

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

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

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

Crooke's hyaline change was studied by immunocytochemistry using an anti-adrenocorticotropic hormone (ACTH) antiserum and five different antisera against cytokeratins. Crooke's hyaline appears in basophil cells of the adenohypophysis in patients with hypercortisolism, presumably as a part of the negative feedback on corticotropin secretion. Previous studies have identified the hyaline material as a simple protein, apparently unrelated to ACTH, and electron microscopy has revealed a loss of secretory granules and an accumulation of 6-9-nm filaments in the cytoplasm of affected cells. In this study, the secretory granules in adenohypophysial cells exhibiting Crooke's hyaline change were labeled by anti-ACTH antibodies, while the hyaline material was positive for cytokeratin with each of the five antisera used. The results suggest that high levels of glucocorticoids may stimulate elaboration of cytokeratins in basophils while they suppress the production and release of ACTH.

Topics: Adenoma, Basophil; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Aged; Cytoplasmic Granules; Cytoskeleton; Female; Humans; Hyalin; Immune Sera; Keratins; Male; Microscopy, Electron; Middle Aged; Pituitary Gland, Anterior; Pituitary Neoplasms

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

The histologic similarities between the craniopharyngioma and the ameloblastoma are well recognized and supported by their common embryologic origin from oral ectoderm. Differences in these lesions include a greater tendency for craniopharyngiomas to be cystic and form ghost cells and calcifications. The keratinizing and calcifying odontogenic cyst (KCOC), a lesion that features proliferating ameloblastic epithelium, ghost keratin, calcification, and cyst formation, may more precisely mimic the craniopharyngioma. The histologic features of twenty-seven craniopharyngiomas were studied. Twenty cases resembled KCOC microscopically. Two examples duplicated the histologic features of infiltrative ameloblastoma, while five showed characteristics of both lesions. This study shows that the range of histologic features in craniopharyngioma includes and spans both odontogenic lesions but more often simulates KCOC. The results suggest that the KCOC and the ameloblastoma may be closely related developmentally.

Topics: Ameloblastoma; Craniopharyngioma; Diagnosis, Differential; Epithelium; Humans; Keratins; Metaplasia; Odontogenic Tumors; Pituitary Neoplasms

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

Topics: Adolescent; Adult; Basement Membrane; Calcinosis; Cell Differentiation; Cell Nucleus; Cerebral Ventricle Neoplasms; Child; Child, Preschool; Collagen; Connective Tissue Cells; Craniopharyngioma; Desmosomes; Epithelial Cells; Golgi Apparatus; Humans; Hydroxyapatites; Keratins; Microscopy, Electron; Neuroglia; Pituitary Neoplasms

Topics: Craniopharyngioma; Humans; Keratins; Neoplasms; Pituitary Neoplasms

Topics: Craniopharyngioma; Humans; Keratins; Neoplasms; Pituitary Neoplasms