bromochloroacetic-acid and Carcinoma--Papillary

Papillary tumor of the pineal region (PTPR) was introduced to the WHO classification in 2007. This rare tumor of little known natural history and unpredictable behavior was described in fewer than 100 cases. Its optimal treatment is not established yet. We report another two cases of PTPR in whom tumors were totally removed via supracerebellar infratentorial approach and both were treated with radiotherapy. In a 37-year-old man the operation was delayed 6 years after the first tumor diagnosis and subsequent shunt placement. He has no complaints 10 years after the onset of the disease. A 45-year-old woman has no complaints 24 months after surgery. Our experience and the data from literature indicate that a total tumor removal is the major prognostic factor.

Topics: Aged; Brain Neoplasms; Carcinoma, Papillary; Female; Humans; Keratins; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Phosphopyruvate Hydratase; Pineal Gland

Papillary squamous cell carcinoma (SCC) (PSCC) of the oral mucosa is a relatively rare but distinct variant of SCC of head and neck. The objectives of this study were to describe the clinicopathologic and immunohistochemical features of a series of patients with oral PSCC and to review the literature on this topic. Retrospective review of patients with clinical and pathologic diagnosis of PSCC (n = 12) between 2000 and 2008 in our institution was conducted. The outcome analysis in a mean follow-up of 56 months (range, 24-131 months) was performed. These patients were 7 women and 5 men, and the mean age at diagnosis was 72.9 years (range, 53-83 years). The cheek and the gingiva were the predominant sites of involvement. At the end of follow-up, 4 patients were found to have local recurrence, and 3 were dead of disease. The estimated 3- and 5-year survival was 91.7% and 76.4% for the whole series, respectively. Histopathologically, the papillary pattern consisted of multiple, thin, delicate filiform, finger-like papillary projections with fibrovascular cores. Besides, the exophytic pattern consisted of the broad-based bulbous to "cauliflower-like" exophytic growth with rounded projections. Immunohistochemically, positivity for CKpan, CKhmw (high molecular weight), and p53, yet negativity for CK8, vimentin, desmin, smooth muscle actin, and S-100 was observed in PSCC. In conclusion, 2 specific histopathologic growth patterns of oral PSCC were identified to separate from conventional SCC. Patients with PSCC have a favorable outcome in relation to exophytic nature and limited invasion of the tumor.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cheek; Female; Gingiva; Humans; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Retrospective Studies; Survival Rate; Tumor Suppressor Protein p53

Papillary tumour of the pineal region (PTRR) is one of the new tumour entities to be included in the latest World Health Organization classification of central nervous system tumours. We report two illustrative patients, a 25-year-old female who presented following a head injury sustained from a fall due to gait disturbances, and a 42-year-old man who presented with headaches. Histology of both cases showed distinct papillary growth patterns with lining of the papillae by multi-layered cuboidal to columnar cells, prominent perivascular rosette and focal true rosette formation. Immunohistochemistry exhibited strong cytokeratin immunoreactivity in addition to CD56, focal S100, glial fibrillary acidic protein and neuron specific enolase positivity which supported a diagnosis of PTPR in both patients. Postoperatively, both patients underwent courses of adjuvant radiation therapy. One patient reported local recurrence of the tumour 23 months after surgery. While PTPR may have been misdiagnosed in the past, clear and consistent characteristics are beginning to be elucidated in the published reports and literature, which have been reviewed. As a relatively new distinct clinicopathological entity, prognostic data are limited and guidelines for treatment protocols are still being investigated in view of its propensity for local recurrence.

Topics: Actins; Adult; Brain Neoplasms; Carcinoma, Papillary; Female; Humans; Keratins; Magnetic Resonance Imaging; Male; Nerve Tissue Proteins; Pineal Gland; Vision Disorders

Papillary tumor of the pineal region (PTPR) is a newly recognized distinct entity in the 2007 World Health Organization nomenclature. This tumor is characterized by epithelial-appearing areas with papillary features and more densely cellular areas that often display ependymal-like differentiation. Ultrastructurally, this rare neuroepithelial tumor possesses neuroendocrine, secretory, and ependymal organelles that likely originate from the subcommissural organ (SCO) near the aqueduct of Sylvius. To date, approximately fifty-seven described cases worldwide have been recognized, with ages ranging from 5 years to 66 years (mean age=32 years). Clinical presentation most often includes headache and obstructive hydrocephalus. The tumor, which is well circumscribed, may be cystic and radiographically is often considered to be consistent with the findings of a pineocytoma. Microscopic evaluation often demonstrates a lesion with papillary areas lined by epithelioid tumor cells with eosinophilic cytoplasm and more cellular areas with cells exhibiting clear or vacuolated cytoplasm. Perivascular and true rosettes may be identified. Distinctive immunohistochemical features including reactivity for keratins (AE1/AE3, CAM 5.2, CK18) and only focal GFAP staining help distinguish this neoplasm from an ependymoma. The relative paucity of data compiled for this tumor makes giving an accurate diagnosis and prognosis a daunting task. We discuss two additional cases of PTPR that presented to us within a three-month span in order to more fully elucidate the possible presentations of this rare entity. Furthermore, we examine now 59 reported cases of PTPR in order to review the current diagnostic and treatment modalities in addition to exploring emerging research encompassing this unusual neoplasm.

Topics: Adult; Biomarkers; Brain Neoplasms; Carcinoma, Papillary; Female; Humans; Keratins; Male; Middle Aged; Pineal Gland

Papillary lesions of the breast represent a heterogeneous group with differing biological behaviour. Correct diagnosis is crucial but may be difficult, as many benign and malignant papillary lesions have similar appearances. Immunohistochemistry plays a useful role in their differentiation. Myoepithelial markers can help in differentiating papilloma from papillary carcinoma, as the former usually shows a continuous layer of myoepithelial cells. In intracystic papillary carcinoma, there is controversy as to the presence of a complete myoepithelial cell layer around these lesions. p63 is the marker of choice as the staining is nuclear, cross-reactivity is minimal, and sensitivity is high. Papilloma may frequently be complicated by superimposed different types of epithelial hyperplasia, which range from usual to atypical or even ductal carcinoma in situ, and they many be morphologically similar. Basal cytokeratins (CKs) are useful to differentiate these entities; as usual hyperplasia is positive for basal CKs with a mosaic staining pattern. CK5/6 is probably the best marker. Neuroendocrine markers (chromogranin A and synaptophysin) may be positive in papillary carcinoma, particularly in the solid type, and there may be some overlap with the ductal carcinoma in situ with spindle cells or endocrine ductal carcinoma in situ. A panel of CK5/6, p63 and neuroendocrine markers can be useful in the diagnostic investigation of problematic papillary lesions of the breast. As the experience with these markers remains rather limited, it is too early to recommend basing treatment choices on these marker studies alone. Complete removal of lesion is probably still the treatment of choice.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Keratins; Neoplasm Proteins; Nerve Tissue Proteins; Papilloma

Thyroid carcinomas have been found incidentally in the cervical lymph nodes during surgery for head and neck squamous cell carcinoma (SCC). Such carcinomas have been considered a metastatic focus for malignant transformation of heterotopic thyroid tissue. We report on cases of so-called occult thyroid carcinoma in the cervical lymph nodes, and review the relevant literature.. We encountered 3 cases of incidental papillary carcinoma in the cervical lymph nodes of patients with oral SCC, and consequently reviewed 75 previously reported cases.. Among 148 patients with oral SCC who had undergone cervical lymph node dissection, 3 were diagnosed with occult thyroid carcinoma. Papillary carcinomas were found in 3, 10, and 3 lymph nodes in cases 1, 2, and 3, respectively. Computed tomography showed 2 tumor-like shadows and 1 calcified mass in the thyroid gland in cases 2 and 3, respectively. These shadows did not enlarge during the 3 to 5 years of observation, and all patients are alive, without any events related to the neck and thyroid gland. Among the reviewed cases, approximately two fifths were histopathologically or clinically free from thyroid carcinoma. Progressive thyroid carcinoma was not detected in any patient.. We propose the possibility that thyroid carcinoma in the cervical lymph nodes is not necessarily metastatic, but may occasionally arise from heterotopic thyroid tissue.

Topics: Aged; Carcinoma, Papillary; Carcinoma, Squamous Cell; Choristoma; Diagnosis, Differential; Histocytochemistry; Humans; Incidental Findings; Keratins; Lymph Nodes; Male; Middle Aged; Mouth Neoplasms; Neck; Neck Dissection; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms

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

We describe herein four cases of an unusual sporadic thyroid tumor that shares the morphologic features of a distinctive follicular cell neoplasm previously proposed as a feasible indicator of familial adenomatous polyposis. We also review five other similar cases reported in the literature. All of the nine patients were young women, aged 16 to 30 years. Grossly, the neoplasms measured 1.5 to 5.6 cm; they were solid and solitary, except one case, which showed two tumor nodules, one in each lobe. Histologically, the lesions were encapsulated, and they exhibited an intricate blending of cribriform, follicular, papillary, trabecular, and solid patterns of growth, with morular (squamoid) areas. Cribriform structures were prominent, being formed by anastomosing bars and arches of cells in the absence of intervening fibrovascular stroma. Follicular areas were usually devoid of colloid, and the papillae were lined by columnar cells. There were focal areas of trabecular arrangement reminiscent of hyalinizing trabecular adenoma. The tumor cells were cuboidal or tall, with frequent nuclear pseudostratification and abundant eosinophilic-to-oxyphilic cytoplasm. The nuclei were usually hyperchromatic, but nuclear grooves, pale or clear nuclei, and intranuclear cytoplasmic inclusions were variably present. Morules with peculiar nuclear clearing caused by biotin accumulation were scattered in the tumors. Vascular and/or capsular invasion were noted in all of the cases except one, and lymph node metastasis was found in two cases. Immunohistochemical stains showed reactivity for thyroglobulin, epithelial membrane antigen, cytokeratins (including 34betaE12), vimentin, estrogen and progesterone receptors, bcl-2, and Rb proteins. Follow-up in seven cases showed that all of the patients were alive with no evidence of disease at 1 to 13 years after diagnosis. Thus, the behavior of this variant seems to be similar to that of conventional papillary carcinoma Because of the distinctive histologic features, we propose naming this tumor the cribriform-morular variant of papillary carcinoma.

Topics: Adenomatous Polyposis Coli; Adolescent; Adult; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Phosphopyruvate Hydratase; Thyroglobulin; Thyroid Neoplasms; Vimentin

Twenty cases of papillary cystic tumor of the pancreas were studied (19 female patients, one male patient; median age, 19.5 years). Most tumors developed in the head or body of the pancreas as well-circumscribed, large masses. Gross examination showed that they were solid, cystic, and hemorrhagic. Preoperative fine-needle aspiration biopsy anticipated the diagnosis in four cases. Histologic examination showed that uniform cells formed solid sheets, and loss of cohesion produced pseudopapillae. Hemorrhage, foam cells, cholesterol granulomas, and entrapped nests of pancreatic parenchyma were often found. Fifteen cases studied immunohistochemically were reactive for vimentin and alpha-1-antitrypsin, 13 expressed neuron-specific enolase, 2 expressed cytokeratin, and 1 expressed S-100 protein. None were reactive for pancreatic hormones, opioid peptides, hormonal receptors, or neuroendocrine markers. Electron microscopic examination in five cases showed oval nuclei, moderate amounts of rough endoplasmic reticulum, and many mitochondria; it also showed that annulate lamellae were common. No diagnostic secretory granules were found. DNA study in nine cases revealed a diploid GO/1 peak in eight and hyperdiploid (diploid index = 1.1) DNA content in one case. Fourteen patients with follow-up were free of disease (mean, 2.6 years). Papillary cystic tumor of the pancreas possibly originates from primordial pancreatic cells and lacks definite evidence of endocrine or exocrine differentiation.

Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin; Biopsy, Needle; Carcinoma, Papillary; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

The diagnosis and classification of bladder cancer are based primarily on histologic and cytologic light microscopy. The significant cytologic alternations are abnormal (increased) DNA content and structural changes in chromatin. Measurements of DNA content carried out by flow cytometry on suspensions of tumor cells and bladder irrigation specimens correlate well with clinical and biopsy findings. Badalament et al (Badalament RA, Kimmel M, Gay H, et al. Cancer 1987;59:2078-2085) reported that a single bladder wash flow cytometry correctly detected 83% of bladder cancers. The technique is most sensitive in detecting early, in situ, and superficially invasive carcinoma. In 100 urologic patients with non-neoplastic disease of the bladder, Klein et al (Klein FA, Herr HW, Sogani PC, et al. J Urol. 1982;127:946-948) reported only two false-positive examinations. Flow cytometry appears to be at least as valuable as conventional urinary cytology, without the need of an experienced cytopathologist. However, as specimens must be collected by bladder irrigation via catheter or cytoscope, the technique is most suitable not for population screening, but in monitoring high-risk populations: industrial workers or others exposed to carcinogens, persons with a history of urothelial tumors, and adult patients referred for urologic examinations because of hematuria, unexplained, recurrent cystitis, or other urologic symptoms. DNA flow cytometry also has been valuable in monitoring the conservative treatment of bladder cancer and of predictive value in the intravesical bacille Calmette-Guérin treatment of superficial carcinomas of the bladder. Dual parameter measurements of DNA content and antigen expression are now under evaluation, as are measurements of chromatin structure alteration, metabolism, and proliferative rate. These promise to discriminate subsets of bladder cancer that may be predictive of clinical behavior.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Blood Group Antigens; Carcinoma, Papillary; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Urinary Bladder Neoplasms

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

Topics: Adenocarcinoma; Cadherins; Carcinoma, Papillary; Carcinoma, Transitional Cell; Humans; Keratins; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Uroplakin II; Urothelium

Papillary renal neoplasm with reverse polarity is a form of recently described tumor. These tumors are defined by GATA3 positivity, negative vimentin staining, and the presence of both papillary structures and a layer of eosinophilic cells with apical nuclei and a granular cytoplasm. In the present report, we review 7 cases of papillary renal neoplasm with reverse polarity that were GATA3+ and vimentin-, consistent with past reports. In all 7 of these cases, we found that these tumors were additionally positive for 34βE12. All 7 of these tumors were categorized as stage pT1. On histological examination, these tumors exhibited branching papillae with apical nuclei. All 7 of these patients were alive on most recent follow-up, with 6 being disease free and one having developed prostate cancer. Together, this overview of 7 additional cases of papillary renal neoplasm with reverse polarity offers further insight into this rare and poorly understood disease.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; GABA Plasma Membrane Transport Proteins; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis.. We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin.. E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.. E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

Topics: Adult; Aged; alpha 1-Antitrypsin; Antigens, CD; beta Catenin; Cadherins; Carcinoma, Papillary; Chromogranin A; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neprilysin; Neuroendocrine Tumors; Pancreatic Neoplasms; Receptors, Progesterone; Synaptophysin; Vimentin; Young Adult

To study epithelial mesenchymal transition (EMT) in breast cancer, molecules such as PRL-3, Snail, Cytokeratin and Vimentin involved in EMT were evaluated.. In this study, m-RNA expression of PRL3 and Snail by RT PCR, protein expression of PRL-3, Snail, Cytokeratin and Vimentin by immunohistochemistry were evaluated on paraffin-embedded tissue sections of 100 patients with breast cancer.. PRL3 m-RNA expression (above cut off level > 2487301.00) and PRL-3 protein expression was noted in 52% and 70% of breast carcinoma patients, respectively. The higher incidence of PRL3 protein than m-RNA expression could be due to post translation modification. Further, Snail m-RNA expression (above cut off level > 1285142.00) and Snail protein expression was noted in 53% and 54% of breast cancer patients respectively and Snail protein expression was found significantly higher in patients with pre-menopausal status. The loss of cytokeratin expression in 32% and gain of vimentin expression in 17% was noted in these patients. Vimentin expression was found significantly higher in patients with stage IV disease, BR score 4 and PR negativity. In multivariate survival analysis, Vimentin expression found as strong indicator of biologically aggressive breast cancer predicting reduced disease free survival (DFS) and overall survival (OS).. In our study reveals that Vimentin expression emerged as significant biomarker for predicting reduced DFS and OS in breast cancer. The study proposes routine evaluation of Vimentin with other predictive parameters can allow use of EMT inhibitors with conventional therapy to revert EMT in breast cancer.

Topics: Adenocarcinoma, Mucinous; Adult; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Carcinoma, Papillary; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Middle Aged; Neoplasm Grading; Neoplasm Proteins; Neoplasm Staging; Prognosis; Protein Tyrosine Phosphatases; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Snail Family Transcription Factors; Transcription Factors; Vimentin

To study the clinicopathologic features of papillary tumor of the pineal region (PTPR).. Three hundred and eighty six cases of pineal region and posterior third ventricle tumors, two newborn and two adult pineal glands were analyzed by HE, PAS and immunohistochemistry of 16 antibodies (EnVision method).. Five cases of PTPR were diagnosed with mixed papillary features and densely cellular areas, and included one recurrent case. In the papillary areas, the vessels were lined by one or several layers of cuboidal/columnar cells; the vessel wall was hyalinized. In the densely cellular areas, sheets or nests of tumor cells were seen. The tumor cells of these five cases were immunoreactive to CK, CK8/18, synaptophysin, MAP2, nestin, S-100, and vimentin. Four cases were immunoreactive to NSE and CgA; and 2 cases were immunoreactive to NF. All five cases were negative for EMA, CK5/6, CEA, and NeuN. Ki-67 labeling index ranged from 1% to 6%.Three patients were alive, and the recurrent one died.. PTPR occurs in patients with over a wide age range, from children to adults, and is more commonly found in male than female. PTPR is composed of both papillary and solid areas, characterized by epithelial cytology, and needs to be differentiated from ependymoma. PTPR may originate from the specialized ependymocytes of the subcommissural organ. The prognostic factors are early diagnosis, complete surgical resection and radiotherapy.

Topics: Adolescent; Adult; Brain Neoplasms; Carcinoma, Papillary; Child; Diagnosis, Differential; Ependymoma; Female; Humans; Immunohistochemistry; Keratin-18; Keratin-8; Keratins; Male; Microtubule-Associated Proteins; Nestin; Pineal Gland; Pinealoma; S100 Proteins; Synaptophysin; Tomography, X-Ray Computed; Vimentin; Young Adult

Papillary tumor of the pineal region (PTPR) is a recently recognized entity. We present the pathologic findings of two cases of PTPR as examples, and discuss the presence of cellular pleomorphism in these tumors. Patient 1 is a 48-year-old man with a pineal region mass. The tumor had unique biphasic patterns, papillary/pseudopapillary areas, and increased mitotic activity. Juxtaposed areas had marked pleomorphism, including nuclear enlargement, smudgy chromatin, nuclear pseudoinclusions, and cytoplasmic vacuolation. Mitoses were absent in these areas. Immunohistochemical staining revealed strong S100 expression. CAM 5.2 and CK18 were strongly positive in a patchy fashion. MIB1 labeling indices were high in classic PTPR regions but very low in pleomorphic areas. Patient 2 was a 35-year-old male with a pineal region tumor characterized by papillary architecture and overall cellular monotony, rare mitoses, and pleomorphism as a more isolated finding, with associated nuclear enlargement and crowding. S100 and CAM 5.2 labeling were present, and MIB1 labeling index was very low throughout the tumor. We discuss the pathologic and phenotypic features of PTPR. Variable pleomorphism may be present, reflected in size variation and nuclear hyperchromasia, but was not accompanied by increased proliferative activity in these cases, suggesting a degenerative phenomenon.

Topics: Adult; Biomarkers; Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pinealoma; S100 Proteins

We report the first case of primary solid pseudopapillary tumor of the ovary with aggressive behavior and fatal outcome in a 45-year-old woman. The patient presented with weight loss, decrease of appetite, and abdominal bloating for the last several weeks. Computed tomography scan revealed an ovarian mass, omental caking, complex ascites, and 2 hepatic lesions. The pancreas was unremarkable. Grossly, the ovarian mass showed severe capsular adhesion, and the cut surface was cystic and solid. On histologic examination, the tumor was composed of diffuse solid pseudopapillary and pseudocystic patterns. The neoplastic cells were uniform and round with very dispersed chromatin. The cytoplasm was faintly pink. There was mild atypia, but the mitotic rate was as high as 62 per 50 high-power field, and the Ki-67 was elevated at 20%. The tumor exhibited severe necrosis. Numerous foci of lymphovascular invasion were also seen. The tumor cells were positive for cytokeratin (focal) and for β-catenin (cytoplasmic and nuclear patterns). They were negative for chromogranin, synaptophysin, thyroglobulin, calcitonin, hepatocyte-paraffin 1, epithelial membrane antigen, calretinin, and α-inhibin. Electron microscopic study revealed nests of tumor cells with oval nuclei. The cytoplasm contained numerous pleomorphic mitochondria interspersed among short strands of rough endoplasmic reticulum. The tumor involved the fallopian tube, omentum, cul-de-sac, and abdominal wall. The pelvic washing was also positive for tumor cells. Despite chemotherapy, the patient's condition had worsened, and she died of her disease 8 months after the initial diagnosis. We discuss the differential diagnosis of this tumor and the hypothesis of its origin.

Topics: beta Catenin; Biomarkers, Tumor; Carcinoma, Papillary; Cell Nucleus; Diagnosis, Differential; Fatal Outcome; Female; Humans; Keratins; Middle Aged; Mitochondria; Ovarian Neoplasms; Ovary

The description of the histological features and the immunohistochemical and molecular analyses of a case of cribriform-morular variant of papillary thyroid carcinoma in an 8-year-old girl with a family history of adenomatous polyposis is presented. The neoplasm was multifocal and bilateral, with a mixed pattern of solid, trabecular, and morular areas. The neoplasm showed angioinvasive behavior, extracapsular infiltration with extension to the perythyroidal muscles, and lymph node metastases. Tumor cells were positive for CAM 5.2, cytokeratins 5/6, TTF-1, HBME-1, galectin-3, and β-catenin. In addition, the molecular tests did not reveal BRAF mutations, RET/PTC rearrangement, APC mutation, or KRAS mutation.

Topics: beta Catenin; Biomarkers; Biomarkers, Tumor; Carcinoma; Carcinoma, Papillary; Child; Disease-Free Survival; DNA Mutational Analysis; DNA-Binding Proteins; DNA, Neoplasm; Female; Galectin 3; Humans; Immunohistochemistry; Keratins; Neck Dissection; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Transcription Factors; Treatment Outcome

Papillary squamous cell carcinoma (PSCC) has rarely been reported in the oral cavity. Herein reported is a case of PSCC in the mandibular gum. A 70-year-old man consulted our hospital because of a papillary tumor in the left mandibular gum. Physical examination revealed an exophytic papillary tumor of the left mandibular gum, and an excision of the tumor was performed. Grossly, the tumor was exophytic and papillary, and measured 1 x 1 x 0.8 cm. Microscopically, the tumor showed exophytic papillary proliferation with fibrovascular cores and consisted of atypical squamous epithelial cells. The tumor cells showed hyperchromasia, nuclear atypia, mitotic figures, apoptotic bodies, cancer pearls, and individual keratinization. Mild stromal invasion was seen. Immunohistochemically, the tumor cells were positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, p63, p53, and Ki-67 (labeling index=40%), but negative for human papilloma virus (HPV). HPV in situ hybridization revealed no signals. Therefore, PSCC was diagnosed. The lateral and vertical margins are negative for tumor cell. The pathological diagnosis was PSCC. The patient was healthy and free from tumor three months after the operation.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Squamous Cell; Gingiva; Gingival Neoplasms; Humans; Keratins; Ki-67 Antigen; Male; Mandible; Transcription Factors; Treatment Outcome; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Luminal cytokeratin (CK) expression in breast papillary lesions, and its potential diagnostic utility among other markers in distinguishing between papillomas and papillary carcinomas, has not been previously evaluated. Such expression was determined in 42 papillary lesions (18 papillary carcinomas and 24 papillomas) by immunostaining with a CK5/p63/CK8/18 antibody cocktail. The mean CK8/18 intensity score and percentage of positive cells were significantly higher in papillary carcinomas (227 and 95%, respectively, vs 86 and 42% in papillomas; both P-values <0.0001), whereas the mean CK5 intensity score and percentage of positive cells were significantly lower (7 and 5%, respectively, vs 107 and 58% in papillomas; both P-values <0.0001). Half (9/18) of the papillary carcinomas expressed p63 vs all (24/24) of the papillomas (P = 0.0001). P63 expression in papillary carcinoma was always (9/9; 100%) focal/limited in nature (expression in <10% of cells), whereas focal expression was seen in only four (17%) papillomas (P<0.0001). Both differential CK (CK8/18 and CK5) expression and p63 were equally sensitive (100%) for the diagnosis of papillary carcinoma, but differential CK expression was more specific (96 vs 83%), resulting in a greater accuracy. However, the best discriminatory power in the distinction from papilloma was achieved when all three markers were used in combination, resulting in 100% sensitivity and specificity values. It is concluded that breast papillary lesions have differential CK expression profiles that, especially in combination with p63, can be useful for their stratification, potentially also in needle biopsy material, in which more accurate and reproducible characterization is needed.

Topics: Adult; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Papilloma; Sensitivity and Specificity

Intraductal papillary mucinous neoplasm of the pancreas is a rare but well-established entity in contrast to intraductal papillary mucinous neoplasm of the biliary tract. The aim of this study was to compare the clinicopathologic features of intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas. Twenty patients who underwent resection for intraductal papillary mucinous neoplasm of the biliary tract were compared with 29 cases resected for intraductal papillary mucinous neoplasm of the pancreas. Clinicopathologic characteristics and resection specimens of all patients were reassessed and immunohistochemically screened for expression of a distinct set of tumor markers. Median ages of patients with intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas were 66 and 62 years, respectively (P < .05). Twelve patients with intraductal papillary mucinous neoplasm of the biliary tract (60%) had neoplasms with infiltrating carcinoma, compared with 6 patients with intraductal papillary mucinous neoplasm of the pancreas (21%, P < .05). Cytokeratin 7 and 20 expressions were equal in biliary and pancreatic intraductal papillary mucinous neoplasms. Cytokeratin 20 expression was mainly found in intestinal-type tumors. Gastric, pancreaticobiliary, and oncocytic subtypes were all observed in the intraductal papillary mucinous neoplasm of the biliary tract group. The distribution was significantly different from the intraductal papillary mucinous neoplasm of the pancreas group. The 3-year overall survival rate of malignant biliary and pancreatic intraductal papillary mucinous neoplasm was 63% and 65%, respectively (P = .798). Positive lymph nodes and a high expression of membranous mucin were associated with a significantly shorter overall survival in patients with malignant intraductal papillary mucinous neoplasm. Finally, p53 and Ki67 proliferation index were both associated with the carcinogenesis of intraductal papillary mucinous neoplasm, whereas DPC4 and CDX2 were not. Clinicopathologic features of intraductal papillary mucinous neoplasm of the biliary tract largely resemble those of intraductal papillary mucinous neoplasm of the pancreas, although intraductal papillary mucinous neoplasm of the biliary tract was associated with a higher malignancy rate at the time of surgical treatment. The level of membranous mucin expression and positive lymph nodes are significant prognosticators in patients with malignant intra

Topics: Adult; Aged; Aged, 80 and over; Biliary Tract Neoplasms; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Female; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Netherlands; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Survival Rate

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

Primary peritoneal serous papillary carcinoma (PPSPC) is a rare primary tumor of the peritoneum that found predominantly in elderly and post-menopausal women. The aim of our study is to review the clinical and pathologic information of 22 patients, and then try to summarize clinical behavior and pathological characteristics of PPSPC, in order to be better recognized of this entity in future. We retrospectively reviewed the data from 22 patients with PPSPC treated at our hospital from 1992 to 2008. All paraffin blocks were recut for periodic acid-Schiff diastase and immunohistochemical staining for CD15, cytokeratin7(CK7), cytokeratin20(CK20), S-100 protein, carcinoembryonic antigen (CEA), CA125, estrogen receptor(ER) and progesterone receptor(PR). The median age of the patients at the time of surgical staging was 56 years (range, 32-77 years). The most common presenting symptoms were abdominal distension (59.1%) and ascites (63.6%). Pretreatment CA125 levels were significant elevated in 90.5% patients. Optimal debulking was performed in 18 patients. All patients were consequently treated with platinum-based chemotherapy. Response to treatment is promising, and the median overall survival of all patients was 21.0 months (95% CI 16.9, 25.1 months). The positive rate of immunohistochemical staining was CD15 95.5%, CK7 90.9%, S-100 protein 68.2%, CA125 59.1%, CK20 31.8%, ER 31.8%, CEA 27.3% and PR 9.1%, respectively. Gynecologist should be aware of PPSPC when abdominal distension, gross ascites and a raised level of CA125 in women without ovarian enlargement. Immunohistochemical staining might be helpful as accessory criteria for the differential diagnosis among the PPSPC, peritoneal malignant mesothelioma (PMM), primary epithelial ovarian carcinoma (PEOC) and peritoneal carcinomatosis from the gastrointestinal tumors (SPCGT). Cytoreductive surgery combined with pre/postoperative platinum-based chemotherapy may be effective for PPSPC patients.

Topics: Adult; Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Carcinoma, Papillary; Cystadenocarcinoma, Serous; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; S100 Proteins; Survival Rate

Topics: Aged; Biomarkers, Tumor; Carcinoma, Papillary; Humans; Keratins; Male; Poroma; Sweat Gland Neoplasms; Thigh

Primary fallopian tube carcinoma is a rare malignancy, representing about 1% of female genital tract malignancies. We present a case report and compare the medical performance with accessible data from the literature as well as present immunohistochemical analysis of estrogen, progesterone, and proliferative together with basic cytokeratin reactions. We found that immunohistochemical expression of ER-beta was dominant over ER-alpha which encourages further evaluations to be performed on a larger number of samples, especially taking into account the very scant progesterone receptor expression we noted. On the basis of the course of disease under study, etiological problems and the possibility of clinical misdiagnosis have been discussed. The low prevalence rate and lack of clear symptoms of this type of carcinoma makes the final clinical diagnosis almost impossible without an intraoperative histopathological study. Multicenter studies are needed to improve the understanding of possible risk factors.

Topics: Aged; Carcinoma, Papillary; Estrogen Receptor alpha; Estrogen Receptor beta; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Receptors, Progesterone

The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

Topics: Adult; Carcinoma; Carcinoma, Papillary; DNA-Binding Proteins; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Neoplasms; Transcription Factors

A 50-yr-old male presented a thyroid mass with dysphasia and hoarseness. He underwent total thyroidectomy and neck node dissection. Pathologically, the tumor had two distinct tumor components with intermingled areas: follicular variant of papillary carcinoma and mucoepidermoid carcinoma. Mucoepidermoid carcinoma composed of columnar cells, mucocytes, and squamoid cells showing solid and cystic lesion. Several small cysts lined by benign ciliated columnar epithelia suggesting that this tumor had originated from solid cell nest were seen around the tumor. By immunohistochemistry, columnar cells and squamoid cells in mucoepidermoid carcinoma were positive for cytokeratin but negative for thyroglobulin, TTF-1 and calcitonin. Positivity of p63 was seen in squamoid cells and basal cells of cysts. Some mucocytes are CEA positive. Tumor cells of papillary carcinoma are positive for TTF-1, thyroglobulin but negative for CEA, calcitonin and p63.

Topics: Calcitonin; Carcinoma, Mucoepidermoid; Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Cell Nucleus; Diagnosis, Differential; Female; Humans; Hyperplasia; Keratins; Membrane Proteins; Neoplasm Proteins; Neoplasms, Multiple Primary; Papilloma

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

Papillary breast lesions remain a source of diagnostic confusion because the full range of epithelial proliferations may arise within, or secondarily involve, papilloma. The expression of p63 and high-molecular-weight cytokeratins (HMWCK) was studied simultaneously in 33 papillary lesions including intraductal papilloma (IP, n = 10), atypical papilloma (AP, n = 8) and intraductal papillary carcinoma (IPC, n = 15) by double immunostaining. The myoepithelial cell nuclei were stained dark brown whereas the cytoplasms of usual ductal hyperplasia (UDH) and myoepithelium were stained purple. The myoepithelial layer was recognized as a dark brown dotted line at the epithelial stromal junction in all IP (10/10), most AP (7/8) and some IPC (7/15), suggesting that the retained myoepithelial layer in the papillary processes does not necessarily guarantee benignity. However, the malignant epithelial cells in AP and IPC were typically recognized as monotonous populations unstained with either chromogen. These monotonous cells contrasted with the proliferating cells of UDH in papilloma, which had intense purple cytoplasm in a mosaic-like fashion. The present data suggest that the double immunostaining with the two popular antibodies p63 and HMWCK is a useful tool for reproducible classification of papillary breast lesions.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; DNA-Binding Proteins; Female; Fluorescent Antibody Technique, Direct; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Mammary Glands, Human; Middle Aged; Molecular Weight; Papilloma, Intraductal; Retrospective Studies; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

We examined myoepithelial status in intraductal papillary carcinoma (IPC) along with the expression of high-molecular weight cytokeratin (HMWK) and neuroendocrine markers, with special reference to the differential diagnosis of solid intraductal papillary carcinoma(SIPC) and intraductal papilloma with usual ductal hyperplasia (IP-UDH). Twenty-six (93%) of the twenty-eight intraductal papillomas (IP) had myoepithelial cells in >70% of the epithelial-stromal interface of the intraluminal proliferating component. Six (29%) of twenty-one SIPC had almost complete myoepithelial layer like IP-UDH at the epithelial-stromal interface. HMWK (34 beta E-12) was diffusely positive in 14 (93%) of 15 IP-UDH, but 16 (76%) of 21 SIPC were completely negative for HMWK. Neuroendocrine markers were positive in 14 (67%) of SIPC, but all 28 IPs were completely negative. If only the presence of myoepithelial cells is emphasized as a benign hallmark, about 30% of SIPCs may be underdiagnosed as IP-UDH. However, by using a combination of myoepithelial markers, HMWK, and neuroendocrine markers, all of the 36 solid intraductal papillary lesions were properly classified as benign and malignant. Solid intraductal papillary lesions meeting at least two of the following criteria are highly likely to be malignant: (1) absence of myoepithelial cells(<10% of epithelial-stromal interface of intraluminal proliferating component), (2) negative HMWK(<10%), (3) positive neuroendocrine markers (>10%).

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mammary Glands, Human; Middle Aged; Molecular Weight; Nerve Tissue Proteins; Papilloma, Intraductal

Mammary tumour samples (11 surgical and five post-mortem) from 16 adult European hedgehogs submitted between 1980 and 2004 were examined. Histologically, the tumours were classified as simple tubulo-papillary carcinomas with local invasive growth. In six cases, tumour cell emboli were present in blood vessels or lymphatic vessels, or both. However, metastasis to regional lymph nodes was found only in one hedgehog. Malignant neoplastic epithelial cells were immunolabelled by antibodies specific for various cytokeratins (CKs), including CK1-8, 10, 13-16, 19 and 20. CK expression did not differ from that in normal mammary gland tissue. CK20 was expressed in the mammary tissue of hedgehogs, in contrast to that of dogs and cats; CK7 immunolabelling, however, which commonly occurs in mammary epithelial cells, was negative. CK20 expression, together with the lack of CK7 as determined by a protein-specific antibody, represented an important difference from the CK profile shown by mammary epithelial cells of other mammalian species, including the dog and cat.

Topics: Adenocarcinoma; Animals; Carcinoma, Papillary; Female; Gene Expression Regulation, Neoplastic; Hedgehogs; Immunohistochemistry; Keratins; Male; Mammary Neoplasms, Animal

Topics: Adenocarcinoma; Aged; Carcinoma, Papillary; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Lymphatic Metastasis; Male; Mucin-1

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 breast tumor resembling the tall cell variant of papillary thyroid carcinoma is a very unusual mammary carcinoma whose histologic and predominant nuclear features mimic a papillary thyroid carcinoma. We report the case of a 64-year-old woman who presented with a palpable nodule in the right breast. Fine needle aspiration disclosed abundant cellularity with isolated cells, sheets, and papillary formations of epithelial cells with nuclear grooves. Histologically, the neoplastic cells were arranged in a solid to papillary architecture, with follicular-like and cribriform areas. The cells were columnar to cuboidal with eosinophilic cytoplasm, clear chromatin, nuclear grooves, and occasional nuclear pseudoinclusions. Tumor cells were positive for cytokeratins, alpha and beta-estrogen receptors, progesterone receptor, androgen receptor, CEA, and bcl-2. We searched for BRAF mutations with negative results. Recognizing the cytologic and histologic characteristics of these peculiar mammary tumors that mimic thyroid carcinomas can avoid unnecessary clinical investigations.

Topics: Breast Neoplasms; Carcinoma, Papillary; Diagnosis, Differential; DNA, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mutation; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-bcl-2; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Thyroid Neoplasms

The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel.. One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies.. An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

Topics: Biomarkers, Tumor; Carcinoma, Papillary; Diagnosis, Differential; Galectin 3; Humans; Hyperplasia; Immunohistochemistry; Keratins; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Reproducibility of Results; Sensitivity and Specificity; Thyroid Gland; Thyroid Neoplasms

The solid papillary variant of ductal carcinoma in situ is an uncommon entity, which usually presents in the seventh or eighth decade and may be associated with invasive mucinous carcinoma. Solid papillary ductal carcinoma in situ (SP-DCIS) shares many morphological features with usual ductal hyperplasia (UDH) involving a papilloma: papillary architecture, solid growth, cellular streaming, and low-grade nuclear features. These similarities can make the distinction between these 2 entities challenging. Recent studies have demonstrated that immunohistochemical staining for cytokeratin 5/6 can distinguish UDH from conventional forms of ductal carcinoma in situ. Most of the epithelial cells of UDH express cytokeratin 5/6, but the tumor cells of ductal carcinoma in situ do not. We tested the hypothesis that the results of staining for cytokeratin 5/6 can distinguish UDH from the solid papillary variant of ductal carcinoma in situ. Immunohistochemical staining of 14 cases of SP-DCIS and 9 cases of UDH (4 involving papillomas) was performed using cytokeratin 5/6 antibody clone D5/16 B4. Strong cytoplasmic or membrane staining was considered positive. The hyperplastic cells in all cases of UDH showed strong staining for cytokeratin 5/6. The percentage of positive cells ranged from 50% to 80%. None of the SP-DCIS tumor cells stained for cytokeratin 5/6; however, many cases did show staining of occasional entrapped, benign epithelial, and myoepithelial cells. We conclude that the absence of strong cytokeratin 5/6 expression by SP-DCIS distinguishes it from its morphological mimic, UDH. Pathologists must guard against misinterpreting SP-DCIS as UDH in those cases in which the carcinoma cells engulf cytokeratin 5/6-expressing residual, native epithelial cells.

Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Precancerous Conditions

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

Diagnostic use of antibodies against aquaporin water channel proteins and PAX-2, a nuclear transcription factor in renal development, was tested in 202 renal neoplasms, using tissue microarray technique. Immunohistochemistry for aquaporin-1, aquaporin-2, PAX-2, CD10, and cytokeratin 7 was performed on 102 clear cell renal cell carcinomas, 44 papillary renal cell carcinomas (among them 34 type 1 and 10 type 2), 24 chromophobe renal cell carcinomas, three collecting duct carcinomas (carcinomas of the collecting ducts of Bellini), and 29 oncocytomas. Aquaporin-1 expression was found in clear cell renal cell carcinomas and papillary renal cell carcinomas of both types (78 and 73%, respectively), but not in chromophobe renal cell carcinomas, collecting duct carcinomas, and oncocytomas. Aquaporin-2 expression was not seen in any of the tested tumors. PAX-2 and CD10 was found in the majority of clear cell renal cell carcinomas (88 and 85%, respectively) but only in few papillary renal cell carcinomas, chromophobe renal cell carcinomas and oncocytomas. Decrease or loss of aquaporin-1 and PAX-2 was shown in higher grades compared to lower grades of clear cell renal cell carcinomas (P<0.0001 and <0.0245, respectively). Cytokeratin 7 was rarely seen in clear cell renal cell carcinomas, type 2 papillary renal cell carcinomas, and oncocytomas, but was found in the majority of type 1 papillary renal cell carcinomas (97.1%) and chromophobe renal cell carcinomas (88%). Aquaporin-1 and PAX-2 expression was found to correlate with nuclear grading for clear cell renal cell carcinomas but not for papillary renal cell carcinomas. No correlation of tumor stage and aquaporin-1 and PAX-2 expression was seen. Aquaporin-1 and PAX-2 are reliable markers for clear cell renal cell carcinomas of lower grades but not for higher grades. CD10 expression remains stable, independent of nuclear grading.

Topics: Adenocarcinoma, Clear Cell; Adenoma, Oxyphilic; Aquaporin 1; Aquaporin 2; Aquaporins; Biomarkers, Tumor; Blood Group Antigens; Carcinoma, Papillary; Carcinoma, Renal Cell; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney; Kidney Neoplasms; Neoplasm Staging; Neprilysin; PAX2 Transcription Factor; Tissue Array Analysis; Transcription Factors

Topics: Adult; Calcinosis; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Ossification, Heterotopic; Pancreatic Neoplasms; Phosphopyruvate Hydratase; Vimentin

We studied 50 papillary lesions (25 papillomas and 25 papillary ductal carcinomas in situ, DCIS) diagnosed at Singapore General Hospital, for immunohistochemical expression of cytokeratin (CK) 5/6, CK14, and 34betaE12. The immunoscore (proportion of stained cells multiplied by staining intensity) was compared between the two groups. Cytokeratin expression was corroborated by confocal microscopy. Results were applied to a separate series of 43 papillary tumors from Hong Kong (HK). CK5/CK6, CK14, and 34betaE12 showed higher immunoscores in papillomas (mean values, 107.6, 186.6, and 113.1, respectively) than papillary DCIS (mean values, 12, 29.6, and 34.5, respectively; P<0.0001, P<0.001, and P<0.02, respectively). A cutoff immunoscore threshold of 50 appeared discriminatory between papilloma and papillary DCIS, and this value was applied to the HK cases, with CK5/CK6, CK14, and 34betaE12 correctly predicting 25 (89.3%), 26 (92.9%), and 27 (96.4%), respectively, of 28 HK lesions labeled as papillomas; while they corroborated 13 (86.7%), 13 (86.7%), and 5 (33.3%), respectively, of 15 HK cases diagnosed as papillary DCIS. Review of discordant cases showed that lesions were small, derived from core biopsies, or disclosed accompanying invasive carcinoma. When both SGH and HK cases were combined as a group, the sensitivity of an immunoscore of 50 or less in the diagnosis of papillary DCIS was 95%, 85%, and 62.5% for CK5/CK6, CK14, and 34betaE12, respectively, while the specificity was 86.8%, 94.3%, and 86.8%, respectively. CK immunohistochemistry can aid in evaluating papillary breast lesions. 34betaE12 does not appear as useful in identifying papillary DCIS.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mammary Glands, Human; Middle Aged; Papilloma, Intraductal; Predictive Value of Tests

To investigate the morphologic features, differential diagnosis, prognosis and histogenesis of papillary renal cell carcinoma (PRCC).. Tumors composed of at least 50% papillae and > 1 cm in diameter were included in this study. Light microscopic observation, immunohistochemical assay of EMA, CK7, CD10, Vim, 34 beta E12 by tissue chip were performed.. Among 516 cases of renal epithelial tumors 33 cases of PRCC were detected. Grossly, hemorrhage, necrosis and multifocality were commonly seen. Besides typical papillae, inconspicuous papillary patterns, such as trabecular, tubular, micronodular and pseudostratified patterns could be seen. Foam cells and psammoma bodies in stroma, and hemosiderin in tumor cells were characteristic. Tumors were of two major types: basophilic type (n = 10), with small cuboid cell and pale cytoplasm (n = 10), 9 of them were low in Fuhrman grading; eosinophilic type (n = 22) with large columnar cells, rich in eosinophilic cytoplasm, 19 of them were high in Fuhrman grading. The remaining case was of clear cell type. The basophilic tumors were all positive for distal tubule marker EMA/CK7, none for proximal tubule marker CD10, 7 tumors positive for Vim. Eosinophilic tumors were positive for EMA/CK7 (9/22), CD10 (10/22) and Vim (6/22). All the tumors studied were negative for 34 beta E12. Follow-up data were available for 24 cases (mean 37 months) with 3-year survival rate of 64.3%, 5-year survival rate of 50%.. PRCC was a distinct malignant entity with unique pathological features. The prognosis of PRCC was worse than that of chromophobe renal cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratin-7; Keratins; Kidney Neoplasms; Kidney Tubules; Male; Middle Aged; Mucin-1; Neprilysin; Survival Rate; Vimentin

Graves' disease is an autoimmune disease predominantly seen in females. All types of thyroid cancers may co-exist with Graves' disease but papillary carcinoma is the most frequent. Vesicular nuclei, nuclear grooves, and papillary formations that may be seen in Graves' disease may lead the pathologist to an overdiagnosis of papillary carcinoma. The differential diagnosis between a true papillary carcinoma and foci mimicking papillary carcinoma in Graves' disease may be challenging by light microscopic features only. This study is designed to determine whether CK19 is effective in the discrimination between the true papillary carcinoma of thyroid and foci resembling papillary carcinoma in Graves' disease. Twenty-five cases with papillary carcinoma and 25 cases with Graves' disease containing foci resembling papillary carcinoma were included in the study. All 25 cases with papillary carcinoma stained positive with CK19, whereas only six of 25 cases with Graves' disease showed weak staining, and the remaining 19 cases were completely negative. It is known that CK19 may show faint staining in benign thyroid lesions such as adenomas. Staining pattern with CK19 together with histopathological findings may be helpful in the differential diagnosis between foci mimicking papillary carcinoma and true papillary carcinoma in Graves' disease.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Papillary; Cell Nucleus; Diagnosis, Differential; Female; Graves Disease; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Gland; Thyroid Neoplasms

To investigate agreement on core biopsy diagnosis of papillary breast lesions, which is acknowledged as a difficult area, and to determine the effect of the use of immunohistochemistry (IHC) to assist diagnosis.. Haematoxylin and eosin (H&E) sections of 129 core biopsies of papillary breast lesions were circulated to four observers who categorized each case as: B2 (benign), B3a (epithelial proliferation, probably benign but requiring biopsy), B3b (epithelial proliferation with cytological or architectural atypia), B4 (probably malignant but insufficient material or artefact to allow diagnosis), B5 (malignant papillary lesion). In all cases (n = 127) IHC was performed for cytokeratin (CK) 5/6, calponin, p63 (myoepithelial markers), and slides recirculated.. There was unanimous agreement in 44% of cases on H&E only which rose to 91% after the use of IHC. Overall, unweighted kappa (Ku; five categories) rose from 0.54 to 0.91. The main effect of IHC was to reduce the use of intermediate categories (B3a, B3b and B4) and allow definitive diagnosis (B2 or B5).. Agreement on H&E sections alone in papillary core biopsies of breast is only 44% (Ku = 0.54) but is significantly increased to 91% (Ku = 0.91) by the use of IHC for CK5/6, calponin and p63.

Topics: Biomarkers, Tumor; Biopsy, Needle; Breast; Breast Neoplasms; Calcium-Binding Proteins; Calponins; Carcinoma, Papillary; Diagnosis, Differential; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratin-5; Keratins; Microfilament Proteins; Observer Variation; Phosphoproteins; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Supposedly, thyrocyte-specific transcripts such as thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) were proposed to be useful for the diagnosis of circulating tumour cells in patients suffering from differentiated thyroid carcinoma (DTC). However, several research groups reported blood-borne Tg transcripts in healthy individuals. This study determines in particular the origin of Tg mRNA in nucleated blood cells and analyses whether other tumour-associated sequences are absent in leukocytes, but widely expressed in DTC. Therefore, expression analyses for Tg, TSH-R, cytokeratin 19 (CK 19), human telomerase reverse transcriptase (hTERT) and oncofoetal fibronectin (onfFN) were carried out using cDNAs derived from (1) leukocyte fractions, (2) 18 follicular thyroid carcinomas (FTCs) and 48 papillary thyroid carcinomas (PTCs), and (3) leukocytes of two thyrocyte-depleted individuals treated for C-cell carcinoma of the thyroid. Expression of onfFN was additionally analysed by semiquantitative RT-PCR and by quantitative fluorescence-based real-time PCR. Tg and TSH-R expression was demonstrated not only in both athyroid individuals, but in all leukocyte subgroups tested, while hTERT was absent in resting CD4+ cells and only weakly expressed in the CD8+ group. CK 19 was notable in each leukocyte population except for resting CD14(+), as well as for activated and resting CD19+ cells. All blood cell fractions proved negative for onfFN mRNA, whereas its presence in thyroid carcinoma was 78/98% (FTC/PTC). Threshold cycle values were calculated at: porphobilinogen deaminase (PBGD) = 25.95+/-0.73 (FTC)/24.55+/-5.43 (PTC) (P = 0.2878); onfFN = 25.48+/-3.15 (FTC)/21.44+/-3.44 (PTC) (*P = 0.0001). Finally, onfFN transcripts were detected in blood samples of six out of nine patients with known DTC metastases, demonstrating a reliable assay functionality. We propose that real-time RT-PCR of onfFN mRNA is superior to other markers in monitoring minimal residual disease in DTC with regard to both assay sensitivity and specificity.

Topics: Adenocarcinoma, Follicular; Antigens, CD; Biomarkers, Tumor; Carcinoma, Papillary; Cell Differentiation; DNA-Binding Proteins; Fibronectins; Humans; Keratins; Neoplasm, Residual; Receptors, Thyrotropin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Telomerase; Thyroglobulin; Thyroid Neoplasms

A very rare case of intraductal oncocytic papillary carcinoma of the liver is reported. A 63-year-old Japanese man was admitted to our clinic because of abdominal pain and jaundice. Imaging techniques revealed a unilocular cystic neoplasm of 14 cm diameter in the medial segment of the left hepatic lobe. Combined percutaneous and endoscopic retrograde cholangiographies revealed the unilocular cystic neoplasm contained a lot of mucus and communicated with the left segmental intrahepatic bile duct, and that mucus filled the left segmental and hepatic ducts. Left lobectomy was performed. The postoperative course was good, and the patient is free of disease 30 months after operation. Pathological examination revealed that the cavity of the neoplasm was continuous with the left segmental intrahepatic bile duct, and that a lot of mucus was present in the neoplasm, as well as in the left segmental and hepatic ducts. The neoplasm consisted of papillary growth of atypical epithelial cells with oncocytic changes. Atypical goblet cells were also recognized. No invasion into the surrounding liver was noted. Non-tumorous intrahepatic bile ducts near the lesion occasionally showed epithelial dysplasia and contained a lot of mucus. Immunohistochemically, the tumor cells were rich in mitochondria and were immunoreactive for cytokeratins 7, 18 and 19, carbohydrate antigen 19-9, and hepatocyte-specific antigen. Some tumor cells were immunoreactive for pancreatic alpha-amylase and lipase. Ultrastructurally, the tumor cells showed numerous mitochondria and mucus droplets. Intraductal neoplasm communicating with the intrahepatic bile ducts has rarely been reported. The present case suggests that intraductal oncocytic papillary neoplasm, as described in the pancreas, may also occur in the intrahepatic bile ducts, and that such hepatic intraductal neoplasm may express hepatocellular and pancreatic acinar phenotypes.

Topics: Adenoma, Oxyphilic; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Ductal; Carcinoma, Papillary; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Mitochondria; Radiography

Squamous cell carcinoma of the oral cavity is one of the most common human neoplasms, and prevention of these carcinomas requires a better understanding of the carcinogenesis process and a model system in which cancer chemoprevention agents can be tested. We have developed a mouse model using the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in the drinking water to induce tumorigenesis in the mouse oral cavity.. 4-NQO was delivered by tongue painting or drinking water to two mouse strains, CBA and C57Bl/6. The incidences of oral cavity carcinogenesis were then compared. In addition, we examined the expression of some of the molecular markers associated with the process of human oral cavity and esophageal carcinogenesis, such as keratin (K) 1, K14, p16, and epidermal growth factor receptor, by immunohistochemistry.. After treatment with 4-NQO in the drinking water, massive tumors were observed on the tongues of both CBA and C57Bl/6 female mice. Pathological analyses indicated that flat squamous dysplasias, exophytic papillary squamous tumors (papillomas), and invasive squamous cell carcinomas were present. Immunohistochemistry analyses showed that 4-NQO changed the expression patterns of the intermediate filament proteins K14 and K1. K14 was expressed in the epithelial suprabasal layers, in addition to the basal layer, in tongues from carcinogen-treated animals. In contrast, control animals expressed K14 only in the basal layer. Moreover, we observed more bromodeoxyuridine staining in the tongue epithelia of 4-NQO-treated mice. Reduced expression of the cell cycle inhibitor, p16, was observed, whereas 4-NQO treatment caused an increase in epidermal growth factor receptor expression in the mouse tongues. Interestingly, similar features of carcinogenesis, including multiple, large (up to 0.5 cm) exophytic papillary squamous tumors and invasive squamous cell carcinomas, increased bromodeoxyuridine staining, and increased K14 expression, were also observed in the esophagi of 4-NQO-treated mice. However, no tumors were observed in the remainder of digestive tract (including the forestomach, intestine, and colon) or in the lungs or livers of 4-NQO-treated mice. These results indicate that this murine 4-NQO-induced oral and esophageal carcinogenesis model simulates many aspects of human oral cavity and esophageal carcinogenesis.. The availability of this mouse model should permit analysis of oral cavity and esophageal cancer development in various mutant and transgenic mouse strains. This model will also allow testing of cancer chemopreventive drugs in various transgenic mouse strains.

Topics: 4-Nitroquinoline-1-oxide; Animals; Bromodeoxyuridine; Carcinogens; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Disease Models, Animal; ErbB Receptors; Esophageal Neoplasms; Female; Immunoenzyme Techniques; Keratin-14; Keratins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mouth Neoplasms; Neoplasm Invasiveness; Tongue Neoplasms

The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-alpha-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63-staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program.

Topics: Actins; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma, Papillary; DNA-Binding Proteins; Epithelium; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Muscle, Smooth; Neoplasm Metastasis; Phosphoproteins; Protein Isoforms; S100 Proteins; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

To study the diagnosis and differential diagnosis of renal epithelial neoplasms.. Ninety-one cases of renal epithelial neoplasms with detailed pathologic records were enrolled. In addition to microscopic examination, Mowy's colloidal iron staining and immunohistochemical studies (CD10, vimentin and CK7) were also performed.. Among the 91 cases, there were 78 (86%) clear cell renal carcinoma cases, 8 (9%) papillary renal carcinoma cases, 4 (4%) chromophobe renal carcinoma cases and 1 (1%) renal oncocytoma case. Sixty-three of the 78 clear cell renal carcinoma cases were positive for CD10 and 69 were positive for vimentin (81% and 88% respectively), with prominent cell membrane staining. The majority (74/78) of clear cell renal carcinoma were negative for CK7. All 17 clear cell renal carcinoma cases showed negative or focal coarse droplet-like staining pattern for Mowy's colloidal iron stain. All 4 chromophobe renal cell carcinoma cases showed prominent cell membrane staining for CK7 and blue reticular staining pattern for Mowy's colloidal iron stain. All of which were negative for CD10 and vimentin. The case of renal oncocytoma failed to react with antibodies to CD10, vimentin and CK7, or Mowy's colloidal iron stain.. CD10, vimentin, CK7 and Mowy's colloidal iron stains have proved to be useful in differential diagnosis of common renal tumors which may not be easily distinguished on the basis of histologic examination alone.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Carcinoma, Papillary; Colloids; Diagnosis, Differential; Humans; Immunohistochemistry; Iron; Keratin-7; Keratins; Kidney Neoplasms; Neprilysin; Staining and Labeling; Vimentin

To investigate whether prognosis in micropapillary urothelial carcinoma is related to the proportion of the micropapillary component (MPC), and to identify the immunohistochemical features of MPC.. This study presents a clinicopathological analysis of 20 patients with micropapillary urothelial carcinoma of the bladder with cystectomy specimens for evaluation. Tumours were stratified on the extent of MPC: focal, <10%; moderate, 10-50%; extensive, >50%; and this was correlated with tumour stage and prognosis. Sixteen males and four females were aged 56-81 years (mean 69 years). All cases had high-grade morphology in the micropapillary carcinoma and typical urothelial carcinoma. All cases with extensive MPC (n = 4) were of a high pathological stage (pT3 or pT4) and died of disease (DOD) or other causes. Eighty percent with moderate MPC (eight of 10 cases) were pT3 or pT4 and 50% DOD or are alive with disease. Eighty-four percent with focal MPC (five of six cases) were pT1 or pTa. In high-stage cases, the most invasive component was MPC. High-stage cases had an 85% risk of being advanced at presentation with micropapillary carcinoma. All pT2 or lower stage cases had micropapillary carcinoma on prior transurethral resections of bladder tumour (TURB). High-stage carcinomas had 30% and 54%, respectively, of surface MPC and urothelial carcinoma in situ, in comparison with 85% and 28% in lower stage carcinomas. Immunohistochemical staining was similarly positive in MPC and typical urothelial carcinoma with cytokeratin (CK)7, CK20, epithelial membrane antigen, carcinoembryonic antigen and cytokeratin 34betaE12. CA125 staining was seen only in MPC in 43% of cases.. Micropapillary urothelial carcinoma is a high-grade carcinoma in which the prognosis is related to the proportion and location of the MPC. Cases with moderate or extensive MPC are at high risk of being advanced at presentation. Cases with <10% MPC and surface MPC have a high chance of detection at an early stage. The morphology and immunohistochemical profile of the MPC suggest that it is a form of glandular differentiation in urothelial carcinoma.

Topics: Aged; Aged, 80 and over; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Carcinoma, Transitional Cell; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mucin-1; Survival Rate; Urinary Bladder Neoplasms

Focal papillary thyroid carcinoma (PTC)-like nuclear alterations have been documented in Hashimoto's thyroiditis; however, the molecular association between PTC and Hashimoto's thyroiditis is poorly understood. The aim of this study was to determine whether molecular expression patterns of PTC are present in association with PTC-like nuclear alterations in Hashimoto's thyroiditis.. The expression of four genes known to be up-regulated in PTC [LGALS3 (galectin3), CITED1, KRT19 (cytokeratin 19) and FN1 (fibronectin-1)] and the human mesothelial cell protein identified by monoclonal antibody HBME1 was evaluated. Immunohistochemistry was performed on 23 cases of Hashimoto's thyroiditis with focal or diffuse Hürthle cell change and PTC-like nuclear alterations, 37 PTC and 18 normal thyroids. Focal expression of galectin3 (GAL3), CITED1, cytokeratin 19 (CK19), HBME1 and fibronectin-1 (FN1) was seen in 87%, 65%, 43%, 26% and 17% of Hashimoto's thyroiditis, respectively, only in thyrocytes showing PTC-like nuclear alterations. In contrast, diffuse expression of GAL3, CITED1, CK19, HBME1 and FN1 was seen in 100%, 95%, 70%, 87% and 89% of PTC, respectively. Normal thyroid tissues did not express any of these proteins. Following immunohistochemistry, four Hashimoto's thyroiditis cases were found to contain foci of PTC. These foci were highlighted by the diffuse and strong expression of PTC-associated proteins, which prompted additional retrospective scrutiny of the haematoxylin and eosin-stained sections leading to appreciation of complete PTC-type nuclear atypia.. Focal PTC-like immunophenotypic changes in Hashimoto's thyroiditis suggest the possibility of early, focal premalignant transformation in some cases of Hashimoto's thyroiditis.

Topics: Adolescent; Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoma, Papillary; Cell Nucleus; Female; Fibronectins; Galectin 3; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Gland; Thyroid Neoplasms; Thyroiditis, Autoimmune

Fine-needle aspiration (FNA) specimens from thyroid nodules arising in Graves' disease (GD) can pose diagnostic difficulties because the cytomorphologic changes in GD may mimic nuclear features of papillary thyroid carcinoma (PTC). In addition, treatment of GD patients with radioactive iodine (RAI) may cause significant cytologic atypia, further increasing the diagnostic difficulty. From March 1999 to April 2002, a total of 14 hypofunctioning nodules in 9 patients with GD underwent FNA; 3 patients had received RAI treatment. Three cases were diagnosed as suspicious for PTC and 11 as benign. Three patients with the diagnosis of suspicious for PTC on FNA underwent surgery and were found to have papillary carcinoma. We assessed all cases to find key cytologic features that can differentiate between nodules with reactive/reparative nuclear atypia from PTC arising in GD. The cytologic features assessed included cellularity, amount of colloid, monotony of the cell population, oncocytic features, cell crowding, lymphocytic infiltration, nuclear elongation, nuclear grooves, pale powdery chromatin, presence of small eccentric nucleoli, and random nuclear atypia. Each feature was semiquantitatively graded on a sliding scale of 0 to 4, with 0 representing absence and 4 representing a predominance of the feature. The mean value of each feature was calculated and the benign and malignant lesions were compared using the unpaired t-test. Four features were found to be statistically significant in the diagnosis of PTC as compared to the benign nodules in GD. The nuclei of PTC in GD show prominent nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli. All other features studied were not found to be statistically significant. There does exist an overlap between the cytologic features of benign nodules and PTC arising in GD. However, adherence to strict diagnostic criteria (nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli) can enable the diagnosis of PTC arising in GD.

Topics: Adult; Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoma, Papillary; Diagnosis, Differential; Female; Graves Disease; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Retrospective Studies; Thyroid Neoplasms; Thyroid Nodule

We report a 75-year-old male with anaplastic carcinoma in an extrathyroid area. Thyroid remained unchanged. The patient is alive without incident of tumor recurrence at 3.5 years after total resection and at 5 years after initial symptom. The tumor developed between the sternocleidomastoid muscle and common carotid artery, and was completely separated from the thyroid. The tumor location was consistent with a branchial cyst. The tumor consisted of two parts; an upper solid tumor and a deep cystic tumor. The former showed anaplastic carcinoma with osteoclast-like giant cells. The latter was consistent with thyroid papillary carcinoma. The center was intermingled with these two carcinomas. Anaplastic carcinoma cells were positive for vimentin and papillary carcinoma cells were positive for keratin, thyroglobulin, and thyroid transcription factor-1. These results remain insufficient to find any conclusions concerning the tumor nature; either ectopic thyroid carcinoma arising from a branchial cyst or occult thyroid carcinoma metastasis. This is rare case in which thyroid anaplastic carcinoma transformed from papillary carcinoma in an extrathyroid area.

Topics: Aged; Branchioma; Carcinoma; Carcinoma, Papillary; Cell Transformation, Neoplastic; Diagnosis, Differential; Humans; Keratins; Male; Nuclear Proteins; Osteoclasts; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Tomography, X-Ray Computed; Transcription Factors; Vimentin

To determine whether a micropapillary component is a prognostic predictor, with particular reference to nodal micrometastasis, in patients with stage I lung adenocarcinomas.. Thirty-five cases with stage I lung adenocarcinomas, obtained from lobectomies or pneumonectomies, and 434 dissected hilar and mediastinal lymph nodes, were retrospectively reviewed. A micropapillary component and nodal micrometastasis were found in 16 (45.7%) and 14 (40%) of the 35 cases, respectively, with nodal micrometastasis in 24 (5.5%) of the 434 lymph nodes, in an immunohistochemical study using an anti-cytokeratin antibody. Ten (62.5%) of the 16 cases with a micropapillary component, and four (21.1%) of the remaining 19 cases, showed nodal micrometastases (P = 0.014). Kaplan-Meier survival curves demonstrated that there was no significant difference between the cases with and without a micropapillary component (P = 0.28). However, the 5 years' survival of the cases with and without nodal micrometastases were 71.4% and 35.7%, respectively (P = 0.03).. A micropapillary component may be a manifestation of aggressive behaviour, as shown by frequent micrometastasis, for stage I lung adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Retrospective Studies; Survival Analysis

Diagnosis of renal epithelial tumours of adult is often easily made. Nevertheless, it can be difficult to distinguish clear cell carcinoma (CCC) and chromophobe carcinoma (CCHRO), or the eosinophilic variants of CCC and CCHRO with papillary carcinoma (CTP) and oncocytoma (ONCO). The objective is to study and validate immunohistochemical phenotypes of these tumours and to evaluate if they are helpful and to define a diagnostic strategy.. 310 tumours (75 CCC, 89 CTP, 50 CCHRO and 96 ONCO) were collected and put on 4 tissue-arrays blocks. Immunohistochemical stainings were performed with some usual antibodies: pancytokeratin AE1-AE3, EMA, vimentin, CD10, CK7, CK20 and RCC (Renal Cell Carcinoma).. Pancytokeratin AE1-AE3 is expressed mainly in CTP (82.5%). The cytoplasmic staining of EMA is seen in almost all CCHRO (98%) and more than half of CTP (57%). Vimentin is rather specific of CCC (54.5%) and CTP (85%) whereas it is negative in ONCO and CCHRO. CD10 is expressed in the majority of CCC (86.5%) and in some of CTP and CCHRO 65 and 39% respectively. CK7 is rather specific of CTP and CCHRO with 79 and 81.5% of positivity rate. Based on statistical analysis, we have built a diagnostical tree allowing to distinguish 79% of tumours using only three antibodies: CK7, vimentin and CD10.. CCC are CK7-/Vim-/CD10+ or CK7-/Vim+; CTP are CK7+/Vim+; CCHRO are CK7+/Vim-; and ONCO CK7-/Vim-/CD10-. In the oncocytoma/chromophobe group, ONCO are more often CK7-/EMA- and CCHRO CK7+/EMA+.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasms, Glandular and Epithelial; Neprilysin; Phenotype; Reproducibility of Results; 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

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.

Topics: Adenocarcinoma, Clear Cell; Antigens, CD; Carcinoma, Papillary; Carcinoma, Renal Cell; Cytoplasmic Granules; DNA Fingerprinting; DNA, Complementary; Gene Expression Regulation, Neoplastic; Humans; Keratins; Kidney Neoplasms; Multigene Family; Nephrectomy; Nephrons; Neprilysin; Oligonucleotide Array Sequence Analysis; Vimentin

The differential expression patterns of cytokeratin 20 (CK20) and 34betaE12 antigen in low-grade papillary urothelial tumors of the bladder are discussed.. A retrospective study of 120 patients with low-grade papillary bladder tumors (45 neoplasms of low malignant potential and 75 low-grade WHO G1 carcinomas) was performed. All tumors were graded in accordance with the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications. The mean follow-up was 76.6 months (range, 36-168 mos), considering for prognostic purposes the time to first recurrence, or relapse-free interval (RFI), and the total number of recurrent patients. Immunohistochemically, normal or abnormal CK20 and 34betaE12 antigen expression patterns were determined for each patient. CK20 (clone IT-Ks) and a high-molecular weight cytokeratin (clone 34betaE12) were the monoclonal antibodies used in the immunohistochemical study.. Seventy-seven of 120 patients (64.2%) experienced a recurrence during follow-up. In recurrence prediction, the differential expression pattern of both cytokeratins showed a high sensitivity (76.6% for CK20 and 80.5% for 34betaE12 antigen) and a high positive predictive value (85.5% for CK20 and 75.6% for 34betaE12 antigen), although specificity was higher for CK20 (76.7%) than it was for 34betaE12 antigen (53.4%). Independent of adjuvant intravesical chemotherapy, these 2 markers showed a strong statistical correlation (p < 0.001) in univariate studies with both the prediction of disease recurrences and RFI.. CK20 and 34betaE12 antigen have proved to be strong predictive markers of disease recurrences when considering different topographic expression profiles, and, in the authors' opinion, these profiles could be incorporated into follow-up clinicopathologic strategies.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Papillary; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Urinary Bladder Neoplasms

Immunohistochemical staining for cytokeratin 19 (CK-19) is a useful ancillary technique for diagnosing papillary thyroid carcinoma (papillary carcinoma) in histologic specimens. Although similar results have been obtained on aspirate smears, to our knowledge the utility of CK-19 immunolocalization in cell block preparations as an adjunct to fine-needle aspiration diagnosis of papillary carcinoma has not been examined.. The purpose of this study was to determine whether CK-19 immunostaining of cell block preparations of thyroid aspirates is a useful ancillary technique for diagnosing papillary carcinoma.. Using a monoclonal antibody to CK-19 and a standard avidin-biotin complex technique, immunostaining was performed on paraffin-embedded cell blocks of 57 cases with the following cytologic diagnoses: (a) papillary carcinoma (20 cases); (b) atypical cytology, cannot exclude papillary carcinoma (19 cases); and (c) nonneoplastic thyroid (18 cases). The staining reaction in each case was graded on the basis of percentage of epithelial cells stained (1+, <10%; 2+, <10%-50%; 3+, >50). Tissue follow-up was available in all cases.. Nineteen (95%) of 20 cases with an unequivocal diagnosis of papillary carcinoma were positive for CK-19 (3+). Tissue follow-up confirmed papillary carcinoma in all 20 cases. Of the 19 cases with a diagnosis of atypical cytology, cannot exclude papillary carcinoma, 7 (37%) cases displayed 3+ immunostaining and subsequent excision confirmed papillary carcinoma in all 7 cases. The remaining 12 cases with 1+ immunostaining included surgically confirmed goiter (6 cases), adenoma (2 cases), lymphocytic thyroiditis (3 cases), and papillary carcinoma (1 case). The follicular cells in 18 cases with a cytologic diagnosis of nonneoplastic thyroid showed 1+ immunostaining. Histologic follow-up of these cases confirmed the nonneoplastic cytologic diagnoses.. Cytokeratin 19 immunostaining of cell block preparations of thyroid aspirates serves as a useful tool for the diagnosis of papillary carcinoma. Strong immunostaining (3+) for CK-19 aids in accurate diagnosis of malignancy in cytomorphologically equivocal cases of papillary carcinoma.

Topics: Biopsy, Needle; Carcinoma, Papillary; Cytodiagnosis; Epithelial Cells; Humans; Immunohistochemistry; Keratins; Paraffin Embedding; Retrospective Studies; Staining and Labeling; Thyroid Neoplasms; Thyroid Nodule; Tissue Fixation

Carcinomas with micropapillary features have been described in the breast, urinary bladder, lung, and ovary. They are characterized by the presence of micropapillary tufts in clear spaces. Unequivocal vascular invasion is usually present at the periphery of the tumor. Consequently, these tumors have a high propensity for lymph node metastases and high-stage disease. The metastatic carcinoma can consist exclusively of the micropapillary component, which may elicit an erroneous diagnosis if located in the bladder or lung, as in the patient presented herein. We present a case of a 59-year-old woman with a history of bilateral breast carcinoma status post-bilateral mastectomy, chemotherapy, and tamoxifen therapy. She presented with urinary frequency, and a pelvic mass was noted. A biopsy of the endometrium revealed a poorly differentiated carcinoma. Urinary bladder biopsies showed a carcinoma with micropapillary features diagnosed as micropapillary transitional cell carcinoma. She presented to M.D. Anderson Cancer Center (Houston, TX) for further treatment recommendations. The urinary bladder and endometrial biopsies both contained carcinomas with micropapillary features. The mastectomy specimen showed an invasive ductal carcinoma with a significant micropapillary component. The tumor cells from the breast, endometrium, and urinary bladder were positive for cytokeratin (CK) 7 and estrogen receptor and negative for CK20. In view of the morphologic and immunohistochemical profile, the carcinoma in the endometrium and urinary bladder were interpreted as metastatic lesions from the breast primary. Carcinomas with a micropapillary component are morphologically identical in the breast, urinary bladder, and lung. However, micropapillary serous carcinoma has a different appearance more akin to borderline tumors of the ovary. Immunohistochemical stains are useful in distinguishing these lesions in that thyroid transcription factor-1 positivity suggests a lung primary, CK7 and estrogen receptor suggest a breast primary, and both CK7 and CK20 positivity suggest a urinary bladder primary. It is important to exclude metastatic carcinomas with micropapillary features before making a definite diagnosis of a primary tumor. Carcinomas with micropapillary features have a propensity for lymph node metastases and advanced stage disease. This article discusses the differential diagnosis of carcinomas with micropapillary features in different organs.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Papillary; Carcinoma, Transitional Cell; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Middle Aged; Receptors, Estrogen; Urinary Bladder Neoplasms

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

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Papillary; Diagnosis, Differential; Female; Galectin 3; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Middle Aged; Thyroid Diseases; Thyroid Neoplasms

To investigate the expression of cytokeratins and ret in thyroid papillary carcinoma (TPC) and their diagnostic value.. During the period of October 1999 to March 2002, 69 cases of TPC (42 cases with adjacent normal thyroid tissue) and 14 cases of nodular goiter with papillary hyperplasia were enrolled into the study. Immunohistochemistry for CK19, CK17, CK8, CK20 and ret was performed in all cases using EnVision and LSAB methods respectively.. The positive rates for CK19 and ret in TPCs were 85.5% and 68.1% respectively, which were significantly (P < 0.01) higher than those in nodular goiter and normal thyroid tissue (25.0% and 5.4% respectively). The expression of CK17 was also observed in a few cases of TPCs (11/69, 15.9%), which was mainly localized in areas of squamous metaplasia, poorly differentiated carcinoma and/or in the small infiltrative foci. The positive rates for CK8 were 75.4% and 26.8% in TPCs and benign thyroid tissue respectively. All cases were negative for CK20.. CK19, CK17 and ret expressions are significantly higher in TPCs than benign thyroid tissue; and this characteristic can have important diagnostic value.

Topics: Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Thyroid Neoplasms

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

Cystic thyroid lesions can harbour an occult papillary carcinoma, which fine needle aspiration (FNA) biopsy may fail to detect. Recently, new markers such as galectin-3 lectin have been proposed to distinguish benign from malignant thyroid lesions of follicular origin. The aim of this study was to assess the role of galectin-3 immunodetection in a series of FNA cytological samples of benign and malignant thyroid cystic nodules.. We retrospectively analysed galectin-3 expression by immunoperoxidase staining on 32 cytological paraffin-embedded samples of cystic papillary carcinoma and on 12 samples of benign cysts, both obtained by FNA biopsy. Specificity, sensitivity, positive/negative predictive values, and accuracy of standard cytological examination and galectin-3 immunodetection were assessed.. Among cystic papillary carcinomas, 29 of 32 samples were galectin-3 positive, whereas standard FNA cytology made a correct diagnosis in only 25 of 32 samples. All the benign cysts were negative for galectin-3. In comparing the sensitivity and specificity of the two methods, it appeared that both had a 100% specificity, whereas the sensitivity of cytological examination alone was 75% versus 89.3% obtained by galectin-3 immunohistochemistry.. Galectin-3 immunostaining represents a valid pre-operative adjunct to pick up malignant cells in those cases where a very poor number of epithelial cells may lead to a cytological misdiagnosis. Therefore, we suggest that in poorly cellular FNA biopsies of simple or complex thyroid cysts, galectin-3 expression by epithelial cells is consistent with a cystic carcinoma and supports surgical treatment indication.

Topics: Adult; Aged; Carcinoma, Papillary; Epithelial Cells; Female; Galectin 3; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Thyroid Neoplasms

Carcinomas of the extrahepatic bile ducts are uncommon neoplasms that are morphologically heterogeneous and associated with a poor prognosis. We have previously shown that the noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts behave as in situ carcinomas and are associated with a better prognosis. We reviewed the clinical records of 13 patients with invasive papillary carcinomas of the extrahepatic bile ducts and analyzed the microscopic features and selected immunohistochemical reactivity (p53, Mib-1, and Dpc4) that might correlate with patient survival. In addition, we present the updated SEER (Surveillance, Epidemiology, and End Results) data of the National Cancer Institute for the invasive extrahepatic bile duct carcinomas compiled from 1975 to 1998. The 13 patients with papillary carcinoma had a male to female ratio of 1:1, and their ages ranged from 33 to 89 years. Painless jaundice and abdominal pain were the most common complaints. Five tumors were located in the distal portion, one in the mid portion, and six in the proximal portion of the common bile duct. One papillary carcinoma arose in the right hepatic duct. The Whipple procedure was performed in six patients, common bile duct resection in six, and right hepatic lobectomy in one. The cell phenotype of the papillary carcinomas was biliary in nine and intestinal in three. One tumor had both biliary and intestinal phenotypes. Four tumors dedifferentiated (two to undifferentiated small cell carcinomas, one to small [oat] cell carcinoma, and one to giant cell carcinoma). Two papillary carcinomas extended into the pancreas and three into the liver. Only one patient had lymph node metastases at presentation. Follow-up was available in 10 patients. Six patients died of disease from 2 weeks to 2 years and 1 month after surgery. Four patients are alive with no evidence of disease from 4 months to 8 years and 8 months after surgery. Of 174 invasive papillary carcinomas compiled by the SEER program, 71 were confined to the ductal wall, and 61 had regional lymph node metastases. Papillary carcinomas confined to the ductal wall have better 10-year relative survival rates than adenocarcinomas limited to the wall (21% versus 12%). Likewise papillary carcinomas with lymph node metastasis have better prognosis than adenocarcinoma with nodal metastases (10-y survival rate of 12% versus 5%). Currently, the histologic type and the stage of the disease are the most important

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoembryonic Antigen; Carcinoma, Papillary; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Invasiveness; Smad4 Protein; Survival Analysis; Trans-Activators; Tumor Suppressor Protein p53

To distinguish common epithelial tumors arising in the kidney may have significant implications, in terms of molecular ontogeny and prognosis. It is important to investigate the distribution of immunoexpression of commonly used markers among renal neoplasms and to develop a useful panel as an adjunct to histologic examination, which could lead to the accurate diagnosis of both primary and metastatic tumors. Immunohistochemical stains for CD10, vimentin (VIM), E-cadherin (E-CD), cytokeratins (CK) 7, 8, 19, and 20, high molecular weight keratin (HCK), and peanut lectin agglutinin (PL) (Arachis hypogaea) were performed on 45 (96 for CK7, CK20) conventional (CC), 20 papillary (PC), and 6 (24 for CK7, CK20) chromophobe renal carcinomas (CPC); 12 oncocytomas (OC); 5 collecting duct carcinomas (CDC), and 25 urothelial carcinomas of the renal pelvis (UC). Reactivity for CD10 was evaluated on the basis of the presence of cell surface staining; that for all CKs, cytoplasmic/membranous staining; and that for PL, luminal staining. Both CD10 and VIM were predominantly expressed in CC and PC; E-CD in CPC, OC, and UC; CK7 in PC, CPC, and UC; CK8 and CK19 in CDC and UC; CK20 in UC; HCK in CDC and UC; and PL in CDC. CC and OC were predominantly CK7-/CK20-; PC, CK7+/20-; CPC, CK7+/CK20- or CK7-/CK20-; and UC, CK7+/CK20- or CK7+/CK20+. CDC showed slight predominance of CK7-/20- over CK7+/CK20-. CC was most frequently CD10+/CK7-/HCK-/PL-; PC, CD10+/CK7+/HCK-/PL-; CPC, CD10-/CK7+/HCK-/PL-; OC, CD10-/CK7-/HCK-/ PL-; CDC, CD10-/CK7+/HCK-/PL+ or CD10-/CK7-/ HCK+/PL+; and UC, CD10-/CK7+/HCK+/PL-. Discriminant analysis suggested that CD10/CK7/HCK/PL may be a useful primary immunopanel for distinguishing among CC, PC, CDC, and UC.

Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Cadherins; Carcinoma, Papillary; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Neprilysin; Peanut Agglutinin; Prognosis; Vimentin

Micropapillary carcinoma or a micropapillary carcinoma component has been reported in the ovary, breast, and urinary bladder and is generally thought to have prognostic significance. However, little has been written on micropapillary differentiation in lung carcinoma. We studied 35 cases of primary lung adenocarcinoma with a micropapillary component seen at the M.D. Anderson Cancer Center. The micropapillary component in these tumors ranged from focal to prominent and was seen at both primary and metastatic sites. This component was not associated with any particular histologic subtype of lung adenocarcinoma. Of the 15 cases with available material, 14 (93%) stained positive for cytokeratin 7, whereas only two of the 15 cases (13%) stained positive for cytokeratin 20. Thyroid transcription factor-1 immunostaining of tumor nuclei was seen in 12 of the 15 cases (80%). Immunostaining was seen in areas both with and without micropapillary differentiation. Thirty-three of 35 patients (94%) developed metastases, which occurred most commonly in the lymph nodes (n = 26), and also in the lung (n = 17), brain (n = 9 cases), bone (n = 9 cases), and other sites. Most metastases had a prominent micropapillary component, irrespective of the extent of the micropapillary carcinoma component in the primary lung tumor. Adequate clinical follow-up information was available for 29 patients. The mean follow-up was 25 months. At their last follow-up, 16 of 29 patients (55%) were still alive with disease, 5 (17%) were dead of disease, and 8 (28%) were alive with no evidence of disease. We believe that a micropapillary component occurring in lung adenocarcinoma should be reported, as this component may be more likely to metastasize. The presence of this component should alert the clinician to search more carefully for metastases and have a closer follow-up on these patients. It is also important to recognize this component in evaluating a metastasis from an unknown primary site, as it should alert the pathologist to a possible primary in the lung in addition to breast, urinary bladder, and ovary.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Bone and Bones; Carcinoma, Papillary; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Neoplasm Metastasis; Nuclear Proteins; Prognosis; Thyroid Nuclear Factor 1; Transcription Factors

We have recently observed that Hürthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features.. Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hürthle cell tumours, tumours with or without some features of Hürthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hürthle cell changes. All Hürthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hürthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hürthle cell neoplasms and rarely seen in non-Hürthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hürthle cell or apocrine-like changes.. All papillary thyroid carcinomas without Hürthle cell or apocrine-like differentiation are reactive for HBME. Hürthle cell tumours and tumours with Hürthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.

Topics: Adenoma, Oxyphilic; Apocrine Glands; Biomarkers, Tumor; Carcinoma, Papillary; Humans; Immunoenzyme Techniques; Keratins; Oxyphil Cells; Thyroid Neoplasms

Hybrid follicular carcinoma (FC) and papillary thyroid carcinoma (PTC) have not been previously well described. Consecutive cases of 29 FC, 12 Hurthle cell carcinomas (HC), 247 PTC and 13 Hurthle cell PTC (HPTC) were reviewed with special attention to the coarse (CC) and fine chromatin patterns (FIC), as well as to the presence of nuclear grooves, pseudoinclusions or optically clear appearance. Limited nuclear features of PTC (LNF-PTC) are defined as areas of tumor with FIC in addition to some other nuclear features, but insufficient for the diagnosis of PTC. Tumors with nuclei showing an admixture of CC and PTC or LNFPTC were submitted for immunostaining for cytokeratin 19, HBME and Ret/PTC. FC and HC contained areas of LNFPTC in 25 tumors and focal PTC in 3 tumors. None of these cases was associated with lymph node metastasis. Areas with CC were found in 54 PTC and 3 HPTC. The rates of vascular invasion and distant metastasis tended to be higher for PTC with areas of coarse chromatin pattern than for PTC without such areas; however, the difference was not statistically significant. Immunoreactivity for cytokeratin 19 and HBME was moderate to strong for PTC and focal areas of PTC or LNFPTC in FC without Hurthle cell changes. Ret/PTC immunostaining was positive in areas of LNFPTC or focal PTC in three FC. Focal PTC or areas of LNFPTC are frequently seen in FC. Likewise, areas of CC are often present in PTC. The presence of these focal areas does not appear to change the clinical behavior of the tumor and therefore does not warrant a change of nomenclature.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Adult; Biomarkers, Tumor; Carcinoma, Papillary; Chromatin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Oncogene Proteins, Fusion; Protein-Tyrosine Kinases; Retrospective Studies; Thyroid Neoplasms

Cell growth and proliferation depend on protein synthesis that is regulated, in part, by two eukaryotic translation initiation factors, eIF-4E and eIF-2alpha. These factors are transiently increased as normal cells respond to growth factors and are constitutively elevated in transformed cells. In cultured cells, eIF-4E facilitates cell cycle progression by increasing the expression of cell cycle promoting proteins including cyclin D1. Our previous study revealed elevated cyclin D1 expression in histologically more aggressive thyroid carcinomas as compared to conventional papillary carcinoma. We hypothesized that the increased cyclin D1 expression might correlate with increased eIF-4E expression. We, therefore studied the expression of eIF-4E by immunohistochemistry in 25 cases of conventional papillary carcinoma (CPC) and 28 cases of aggressive thyroid carcinomas (ATC), the latter included 11 tall cell/columnar cell variant of papillary carcinoma, 5 insular carcinomas, and 12 anaplastic carcinomas. We also analyzed the expression of eIF-2a in the same samples as this factor is usually regulated similarly to eIF-4E in cell culture models. Of the 25 CPC, 13 were eIF-4E positive (11 weakly and 2 strongly), and 19 were eIF-2a positive (14 weakly and 5 strongly). Conversely, of the 28 ATC, 25 were eIF-4E positive (4 weakly and 21 strongly), and 23 were eIF-2alpha positive (4 weakly and 19 strongly). There was a significantly increased expression of both eIF-4E (p < 0.001) and eIF-2alpha (p < 0.001) in ATC compared to CPC, suggesting that these translation initiation factors may play a role in the progression of thyroid cancer.

Topics: Antibody Specificity; Blotting, Western; Carcinoma; Carcinoma, Papillary; Cell Division; Cyclin D1; Eukaryotic Initiation Factor-2; Eukaryotic Initiation Factor-4E; Humans; Immunohistochemistry; Keratins; Peptide Initiation Factors; Thyroid Neoplasms

Some investigators have found an increased incidence of papillary carcinoma (PC) of the thyroid in patients with Hashimoto's (autoimmune) thyroiditis (HT), which raises the possibility that there may be more than an incidental association between these 2 diseases. In this study, we analyzed the pathology of Hashimoto's-associated thyroid carcinomas to see if these tumors showed any distinctive features. The possible significance of solid cellular nodules as preneoplastic lesions in patients with HT was investigated. A review of all the cases of HT during a 16-year period yielded 30 PC and 3 follicular carcinomas (FC). Within the PC there were 7 (23%) follicular variants. Twenty (67%) of the PC showed various degree of intratumoral fibrosis, ranging from thick fibrous septa separating tumor nodules to almost complete obliteration of the tumor by the fibrosis, with only microscopic residual tumor nests. In most of the cases, the desmoplastic response within the tumors was of the fibromatosis-like type with dense hyalinized collagen and bland-appearing spindle cells. All the tumors, independently of the degree of fibrosis, showed the nuclear features of PC. No correlation was found between the degree of fibrosis in the tumors and the thyroid gland outside the tumors. There were tumors with marked fibrosis without fibrosis outside the tumors. Four cases of PC (13%) showed a growth pattern characterized by cystic spaces with thick hyalinized walls and focal papillary hyperplasia lined by flat and cuboidal epithelium, reminiscent of a vascular neoplasm. There were 4 atypical solid microscopic nodules with confluent cellularity; 2 of them associated with a PC and the other 2 with diffuse HT without PC. These nodules were composed of cells with clear nuclei and occasional grooves without nuclear pseudoinclusions. By immunohistochemistry, 2 of 3 nodules showed cytoplasmic reactivity for cytokeratin 19, and 2 of 3 nodules were positive for the RET/PTC (rearranged during transfection, papillary thyroid carcinoma) antibody. In summary, HT-associated PC may frequently display prominent stromal desmoplasia and a pseudovascular pattern, both of which can present diagnostic difficulties if the cytologic features of PC are not recognized because of the marked obliteration of the tumor by the fibrosis. Atypical nodules may represent a precursor lesion of PC in patients with HT.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nuclear Receptor Coactivators; Oncogene Proteins; Thyroid Neoplasms; Thyroiditis, Autoimmune; Transcription Factors

Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Renal Cell; Cell Division; Cell Nucleus; Cytoplasm; Female; Humans; Keratin-7; Keratins; Ki-67 Antigen; Kidney Neoplasms; Kinetics; Macrophages; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Nucleolus Organizer Region; Silver Staining; Survival Rate

We report the clinicopathological and immunohistochemical characteristics of 12 cases of a recently recognized entity, oncocytic papillary thyroid carcinoma (PC) with lymphoid stroma (Warthin-like tumour).. The cases were retrieved from the surgical pathology files of our departments. There were 11 female patients and one male patient; they ranged in age from 45 to 85 years (mean 64.2 years). The immunohistochemical profile demonstrated positivity of tumour cells for cytokeratins, thyroglobulin, Leu-M1 and anti-mitochondrial antigen. S100 protein-positive stromal dendritic/Langerhans cells were uniformly present. Polymerase chain reaction, in situ hybridization, and immunohistochemistry for Epstein-Barr virus (EBV) detection revealed no significant positive signal. MIB-1 labelling index was low, compatible with that of 'classical' PC.. Warthin-like tumour is a rare variant of PC, occurring predominantly in elderly women. Its histological features are distinct and well recognizable, differentiating this tumour from a more aggressive tall-cell variant of PC. The apparent indolent behaviour seems to be consistent with the presence of dendritic/Langerhans cells and with low proliferative activity. A possible role of EBV in pathogenesis of this lesion was not proven. Further studies are necessary to determine the prognosis and metastatic potential of this neoplasm.

Topics: Adenolymphoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Middle Aged; Mitochondria; Prognosis; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

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

We report the case of a 78-year-old man who developed a breast mass 12 months after hormonal therapy for palliation of prostatic adenocarcinoma. On histologic and immunohistochemical examination, the breast tumor revealed a unique collision tumor composed of metastatic prostatic adenocarcinoma and solid papillary breast carcinoma.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Breast Neoplasms, Male; Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Male; Mastectomy, Radical; Neoplasms, Multiple Primary; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone

This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 <7> and 45, XY, -8, add(12)(q-ter)<10> for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished.

Topics: Aged; Biomarkers; Carcinoma, Papillary; Carcinoma, Renal Cell; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 12; Diagnosis, Differential; Humans; Immunohistochemistry; Karyotyping; Keratin-7; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Lectins; Male; Mucin-1; Neoplasms, Multiple Primary; Plant Lectins

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

Malignant rhabdoid tumor (MRT) in the neck region is very rare. We report a case of MRT in a 60-year-old woman who had a history of papillary carcinoma of the thyroid gland 7 years previously. One year before admission, in 1995, thyroid carcinoma recurred, and the tumor contained a small undifferentiated region with rhabdoid features. The tumor in 1996 consisted of round to oval rhabdoid cells with abundant cytoplasm, and the growth pattern was diffuse and infiltrative, with no papillary structures. We therefore concluded that the lesion was MRT, transformed from papillary thyroid carcinoma.

Topics: Aged; Carcinoma, Papillary; Cytoplasm; Female; Humans; Keratins; Microscopy, Electron; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Phosphopyruvate Hydratase; Rhabdoid Tumor; Submandibular Gland Neoplasms; Thyroid Neoplasms; Vimentin

Topics: Aged; Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Differentiation; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Vaginal 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

Solitary papillary hyperplastic thyroid nodules (SPHTNs) are frequently encountered in children and teenagers. Although the histologic features are well described, to the best of our knowledge, cytologic findings have not been reported.. To review the cytologic features of histologically proven SPHTNs and to identify the potential diagnostic pitfalls in cytologic diagnosis.. Fine-needle aspiration cytology of 3 histologically proven SPHTNs was reviewed.. Two girls and 1 boy (ages 11, 12, and 15 years) were affected. The cytologic diagnosis in all 3 cases was suspicious for papillary thyroid carcinoma (PTC). The spectrum of cytologic findings included broad flat sheets and 3-dimensional clusters with fire flares. There was mild to moderate nuclear pleomorphism and nuclear atypia. Short nonbranching papillae with transgressing vessels shown to represent hyperplastic papillae on histologic sections were identified in all cases. The background contained giant cells, histiocytes, and watery and inspissated colloid. Although nuclear grooves were identified in occasional cells, intranuclear inclusions were absent. A cell block section (1 case) and histologic sections of SPHTNs (2 cases) were immunohistochemically negative for cytokeratin 19.. Fine-needle aspiration of SPHTNs may be difficult to interpret accurately and can result in false-positive diagnosis of PTC. Although it shares several cytologic features with PTC, the presence of fire flares and short nonbranching papillae, as well as lack of intranuclear inclusions and watery and inspissated colloid in SPHTN appear to be useful features that are helpful in distinguishing SPHTN from PTC. Negative immunohistochemical staining for cytokeratin 19 is useful in excluding a diagnosis of PTC.

Topics: Adolescent; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Papillary; Child; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Thyroid Nodule

Topics: Antigens, Nuclear; Biomarkers, Tumor; Carcinoma, Papillary; Diagnosis, Differential; Drosophila Proteins; Humans; Immunohistochemistry; Keratins; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Thyroid Neoplasms

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

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

In 1999, the World Health Organization (WHO) published a new classification of papillary urothelial tumors of the urinary bladder. Intended to represent a reproducible, easy-to-use classification system that better separates patients with true malignancies (bladder cancer) from those patients who are at an increased risk for developing bladder cancer, problems in the differential diagnosis of various lesions remained. Probably the most critical distinction is between papillomas, papillary urothelial neoplasms of low malignant potential (lmp), and grade I papillary carcinomas. Conversely, problems in the distinction between reactive atypia, atypia of unknown significance, and dysplasia, as well as the distinction of dysplasia from carcinoma in situ (CIS), are unresolved. Whether urothelial basal cell status assessment on hematoxylin and eosin-stained slides completed by cytokeratin immunohistochemistry with anticytokeratin clone 34betaE12 may help to improve some of the previously mentioned diagnostic dilemmas was investigated. Basal cell status assessment was helpful in the differentiation between dysplasia and CIS. In dysplasia, CK IHC showed a predominantly basal labeling pattern, whereas in CIS, labeling of all urothelial layers was seen. Basal cell status assessment could separate 2 groups of pTa GIb papillary carcinoma. Group 1 with a continuous basal CK labeling and a low MIB-1 labeling index (LI) was compared with group 2, with a diffuse labeling pattern and a significantly higher MIB-1 LI. Whether group 1 carcinomas should better be assigned to the group of papillary urothelial neoplasms of lmp is discussed.

Topics: Antigens, Nuclear; Biopsy; Carcinoma, Papillary; Diagnosis, Differential; Humans; Hyperplasia; Immunohistochemistry; Keratins; Ki-67 Antigen; Nuclear Proteins; Papilloma; Urinary Bladder Neoplasms; Urothelium; World Health Organization

The morphologic distinction between papillary and follicular neoplasms of the thyroid gland can be difficult, especially on small biopsy specimens or in fine-needle aspirations. To determine whether immunohistochemistry could help in achieving the correct diagnosis, we characterized the staining pattern for a series of papillary and follicular neoplasms of the thyroid gland. A pilot study was performed using a panel of antibodies, including high-molecular-weight keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20, AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK showed strong differential staining between follicular and papillary neoplasms. HMWK stained 91% of papillary carcinomas, including follicular variants, with a median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms with a median of 45% positive cells. HMWK stained only 20% of follicular neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed strong, although patchy, staining with HMWK and involucrin, whereas those follicular neoplasms that did have staining showed a weak, diffuse pattern of staining. We believe that HMWK, and involucrin to a lesser degree, could be useful in differentiating papillary from follicular neoplasms, especially for cytologic cell block material or for cases in which the architectural pattern is follicular.

Topics: Adenocarcinoma, Follicular; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Protein Precursors; Thyroid Neoplasms

Thyroid anaplastic (undifferentiated) carcinomas (TACs) comprise a morphologically heterogeneous group of tumors, which can arise in the background of differentiated papillary or follicular carcinoma. The thyroid epithelial differentiation varies in these tumors and has not been completely characterized. In this study, we immunohistochemically analyzed different variants TACs from 35 patients by using antibodies specific to 9 different keratin polypeptides, epithelial membrane antigen, thyroid transcription factor I (TTF-1), and thyroglobulin. These tumors were histologically divided into 3 categories: squamoid-cohesive (SC, 13 tumors), spindle cell sarcomatous (SS, 8 cases) and intermediate group, including tumors with giant cells and solid epithelioid components (GC, 18 tumors); 4 tumors had 2 components. The patients ages ranged from 40 to 89 years, with a mean age in all groups of 70 years. TTF-1 was present in only 2 of 9 of the SC tumors, and absent in all other TACs, but was present in entrapped differentiated components. Thyroglobulin was absent in all but 1 case. A complex keratin (K) pattern of stratified epithelia was typically seen in the SC tumors with extensive K7, K8, K17, K18, and K19, and variable K13 and K14 expression; EMA was also present. K16 was limited to squamous pearls in 1 tumor, and K10 was absent. The GC carcinomas typically had K8 and K18, whereas the expression of K7 was variable and that of K14, K17, and K19 sporadic; EMA was variably present in half of the cases. The keratins in spindle cell sarcomatous tumors were usually limited to K7, K8, and K18, often in limited numbers of cells. EMA was present in 1 case only. These results indicate a complex pattern of keratins in squamoid and giant cell TACs, similar to papillary carcinoma and suggesting the possibility of relationship. There was a progressive loss of epithelial differentiation and keratins in sarcomatoid TACs. Loss of TTF-1 is a nearly uniform feature of TAC and disallows the use of this marker to pinpoint a thyroid origin of these tumors.

Topics: Adenocarcinoma, Follicular; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Female; Fluorescent Antibody Technique, Direct; Humans; Keratins; Male; Middle Aged; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid gland, and fine-needle aspiration biopsy (FNAB) often is the initial diagnostic method used in its detection. Prior studies have shown that immunohistochemical staining for various cytokeratins in general, and cytokeratin 19 (CK19) in particular, can be applied as an ancillary technique for diagnosing papillary thyroid carcinoma in histologic specimens. In the current study the authors assessed the diagnostic utility of CK19 to detect papillary carcinoma effectively in cytologic preparations of thyroid FNABs.. Immunocytochemical staining with CK19 was performed on cytologic aspirates from 37 papillary thyroid carcinomas and 36 other lesions of the thyroid (14 follicular adenomas, 10 multinodular goiters, 5 cases of Hashimoto thyroiditis, 6 oncocytic [Hürthle cell] neoplasms, and 1 follicular carcinoma). All cases included in the study had a corresponding histopathology specimen.. Positive immunocytochemical reactivity for CK19 was identified in 34 of 37 papillary carcinomas and in 1 of 36 other thyroid lesions (sensitivity of 92% and specificity of 97%). Although the strongest reactivity was obtained in methanol fixed thin layer preparations, the antibody also was effective in detecting papillary carcinoma in alcohol fixed and air-dried smears. The single false-positive case was a follicular adenoma with focal areas of papillary hyperplasia. All other aspirates including those from cases of Hashimoto thyroiditis, multinodular goiter, follicular adenoma, oncocytic neoplasms, and follicular carcinoma were negative.. CK19 is an effective, highly sensitive, and specific ancillary tool for the diagnosis of papillary carcinoma in thyroid FNABs.

Topics: Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Papillary; Cytodiagnosis; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Thyroid Neoplasms

A 70-year-old woman presented with metastatic psammoma body-rich papillary carcinoma in a supraclavicular lymph node. No primary site was evident. The tumour showed strong staining for CA125 and weak staining for thyroglobulin. Prompted by this case we aimed to assess the reliability of immunostaining for CA125 and thyroglobulin in making the distinction between thyroid and ovarian papillary carcinoma.. Nine papillary carcinomas of the thyroid and 17 serous papillary carcinomas of the ovary were stained for CA125 and thyroglobulin, as well as CAM 5.2, LP 34, carcinoembryonic antigen (CEA), S100 and diastase/periodic acid-Schiff. Nine of nine thyroid carcinomas stained for thyroglobulin; in addition CA125 was positive in four of nine. Normal surrounding thyroid also showed some reaction. Seventeen of 17 ovarian serous carcinomas were positive for CA125; in addition one case showed moderately strong staining for thyroglobulin. Mucin stains were positive in 14/17 ovarian serous carcinomas, but negative in all thyroid carcinomas. The other antibodies assessed showed no useful differences in staining frequency.. Many cases of papillary carcinoma of the thyroid show CA125 staining, and this feature therefore has little positive predictive value for an ovarian origin. Occasional cases of ovarian papillary carcinoma may show staining for thyroglobulin, and this result should therefore be interpreted cautiously.

Topics: Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Mucins; Ovarian Neoplasms; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

A peculiar case of papillary carcinoma arising in the parotid gland is reported. A 68-year-old woman presented with a right, painless, parotid mass, measuring approximately 3 cm in greatest diameter. A conservative parotidectomy was performed. Histologically, the neoplasm showed exophytic papillary projections into a cavity. The cells were focally suggestive of epidermoidal differentiation, whereas a transitional differentiation was noted in other portions, as in bladder papilloma. Immunohistochemical studies showed strong positivity of the neoplastic cells for cytokeratin and weak positivity for PCNA and Mib-1. We classified this neoplasm among the papillary tumors with a low-grade of malignancy.

Topics: Aged; Antigens, Nuclear; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Nuclear Proteins; Parotid Neoplasms; Proliferating Cell Nuclear Antigen

The follicular variant of papillary carcinoma (FVPTC) is characterized by follicular growth pattern and tumor cells with appropriate nuclear features of papillary carcinoma. However, occasionally these lesions may show focal or multifocal instead of diffuse distribution of nuclear features of papillary carcinoma. Such lesions can be underdiagnosed as benign follicular nodule. Previous studies have shown that cytokeratins, especially 19, are helpful in differentiating papillary carcinoma from other benign and malignant follicular patterned lesions. In this study, we applied monoclonal antibodies to CK5/6/18, CK18, CK10/13, CK20, CK17, and CK19 to paraffin sections of formaldehyde-fixed tissue from 26 cases of FVPTC with multifocal distribution of papillary cancer nuclei, 10 cases of usual variant of papillary carcinoma, 1 case of Warthin's tumor-like papillary carcinoma, and 2 cases of the columnar cell carcinoma. CK19 stained strongly and diffusely all cases of papillary carcinoma. FVPTC cases showed strong staining of the areas with papillary cancer nuclei in all cases and moderate to strong staining in areas of tumor without obvious nuclear features of papillary cancer. Normal thyroid parenchyma adjacent to the tumor nodule showed focal staining in most cases; however, tissue away from the tumor nodule failed to show any staining. All cases of usual type of papillary carcinoma, 2 of columnar cell carcinoma, and 1 Warthin's tumor-like papillary carcinoma showed strong and diffuse staining with CK19 and failed to show any staining of adjacent normal thyroid parenchyma. Similar but less intense staining patterns were seen with CK17 and CK20. The control group, consisting of cases of follicular adenoma, follicular carcinoma, and hyperplastic nodule, showed no staining with CK19. We suggest that if one is using immunohistochemistry to aid in the diagnosis of cases of FVPTC with multifocal distribution of nuclear features of papillary cancer, an antibody panel comprising CKs 17, 19, and 20 may prove helpful. In addition, we hypothesize that the staining of adjacent nontumorous thyroid parenchyma with CK19, seen only in cases of FVPTC, suggests that some factors secreted/produced by this particular tumor may lead to modification in keratin expression of surrounding follicular epithelium.

Topics: Biomarkers, Tumor; Carcinoma, Papillary; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Predictive Value of Tests; Thyroid Neoplasms

Cholangiocarcinomas may be extrahepatic or intrahepatic; the latter are further divided into hilar and peripheral types. Peripheral cholangiocarcinomas often resemble adenocarcinomas arising in other organs. Although clear cell changes may occur in hepatocellular carcinoma and extrahepatic cholangiocarcinoma, peripheral cholangiocarcinomas with clear cell change are rare. In such cases, an extrahepatic primary carcinoma must be excluded. We present a patient with a large, clear cell papillary carcinoma in the liver. Extensive workup of the patient for other possible primary sites including kidneys, adrenals, thyroid, prostate, or urinary bladder failed to indicate any other neoplasm. The patient is alive without evidence of disease 30 months after complete resection. The histological, immunohistochemical, and electron microscopic results were most consistent with a neoplasm in the cholangiocarcinoma family. To the best of our knowledge, a clear cell papillary peripheral cholangio carcinoma has not been described previously. This neoplasm may be related to the recently described clear cell carcinomas of the gallbladder and extrahepatic bile ducts.

Topics: Adenocarcinoma, Clear Cell; Aged; Antibodies; Biomarkers, Tumor; Carcinoma, Papillary; Cholangiocarcinoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Periodic Acid-Schiff Reaction

Adenocarcinomas may arise primarily from the urinary bladder, but secondary involvement from adenocarcinomas arising in adjacent organs is more common. In the present study we tried to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas arising from the surrounding organs, based on their antigen profiles in routinely processed, paraffin-embedded tissue specimens. We analysed the staining results using stepwise linear discriminant analysis.. We investigated the usefulness of a panel of antibodies against cytokeratin 7, E48, cytokeratin 20, PSA, PSAP, CEA, vimentin, OC125 and HER-2/neu, to discriminate primary bladder adenocarcinoma from adenocarcinomas arising from the prostate, urachus, colon, cervix, ovary and endometrium. In the differential diagnosis with urinary bladder adenocarcinoma, an overall correct classification was reached for 77% and 81% of urachal and colonic carcinomas, respectively, using CEA, for 93% of prostatic adenocarcinomas using PSA, for 82% and 70% of cervical and ovarian adenocarcinomas, respectively, using OC125, and for 91% of endometrial adenocarcinomas using vimentin. Adding other antibodies did not improve the classification results for any of these differential diagnoses.. For the surgical pathologist, a panel of antibodies consisting of CEA, PSA, OC125 and vimentin is helpful to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas originating from prostate and endometrium, less helpful in differentiation with urachal carcinoma, and not helpful in differentiation with colonic, cervical and ovarian carcinoma.

Topics: Abdominal Neoplasms; Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Cell Adhesion Molecules; Diagnosis, Differential; Endometrial Neoplasms; Female; Glycoproteins; GPI-Linked Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms, Unknown Primary; Ovarian Neoplasms; Prostate; Prostate-Specific Antigen; Receptor, ErbB-2; Urachus; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Vimentin

A case of papillary squamotransitional carcinoma of the vagina is reported. The immunohistochemical profiles (cytokeratin-7 and -20) and the detection of human papillomavirus 16 support its close relationship to conventional squamous cell carcinoma. The lesion is compared to previously reported cases of papillary transitional cell carcinoma of the vagina and papillary squamotransitional cell carcinoma of the cervix.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Papillomaviridae; Urethra; Vaginal Neoplasms

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

The expression of simple and stratified epithelial-type cytokeratin (CK) intermediate filaments was evaluated by immunohistochemistry in a series of 41 papillary carcinomas, 10 follicular carcinomas, 2 poorly differentiated carcinomas and 34 specimens of normal thyroid parenchyma and lymphocytic thyroiditis. The aim of the study was to establish the CK profile of normal thyroid and thyroid carcinomas in order to clarify the putative application of CK immunostaining in diagnostic surgical pathology, and to evaluate whether the process of neoplastic transformation and tumour progression in the thyroid may be associated with any particular change in CK expression. Normal thyroid strongly expressed simple epithelial-type CKs 7 and 18 and, to a lesser degree, CKs 8 and 19, but did not express stratified epithelial-type CKs. The same pattern was found in lymphocytic thyroiditis, though the CK 19 immunoreactivity was stronger in these lesions than in the normal thyroid. Papillary and follicular thyroid carcinomas shared the expression of simple epithelial-type CKs 7, 8, 18 and 19. Immunoreactivity for CK 19 was frequently stronger and more widely distributed within each particular tumour in papillary than in follicular carcinomas, but it could also be detected, at least focally, in every follicular carcinoma. Strong expression of CK 19 highlighted small foci of papillary carcinoma not easily identifiable by conventional histological examination. Stratified epithelial-type CKs 5/6 and 13 were detected in a high percentage of papillary carcinomas, in contrast to their absence in follicular carcinomas and normal thyroid. The CK pattern was similar in primary and metastatic papillary carcinomas. We conclude that papillary carcinoma of the thyroid presents a distinct CK profile that may be used for diagnostic purposes.

Topics: Adenocarcinoma, Follicular; Carcinoma, Papillary; Epithelium; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Reference Values; Thyroid Gland; Thyroid Neoplasms; Thyroiditis

Concurrent medullary and papillary carcinomas of the thyroid gland are rare and occurrence of the medullary and medullary-papillary carcinoma, as far as we know, has not been previously described. The medullary carcinoma was found in the upper part of the right lobe and the mixed medullary-papillary carcinoma in the left lobe of thyroid gland. Immunohistochemistry revealed calcitonin positivity in the medullary parts of the carcinoma and thyroglobulin positivity in papillary structures. Both light microscopy and immunohistochemistry observation distinguished these two cell lineages. The patient was treated with radiotherapy but died 18 months after first symptoms. Metastases were identified in the liver, mediastinal lymph nodes and soft tissues and micro-metastases in the lungs. The authors discuss histogenesis of mixed thyroid carcinomas.

Topics: Biomarkers, Tumor; Calcitonin; Carcinoma, Medullary; Carcinoma, Papillary; Chromogranins; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Multiple Primary; Thyroglobulin; Thyroid Neoplasms

Papillary thyroid carcinoma (PTC) is a somewhat puzzling disease, combining a propensity to metastasize with an indolent clinical course. The often pronounced T cell-dominated inflammatory infiltrate seen in PTC tumors has prompted us to search for signs of a tumor-induced immune response. In previous studies, we have demonstrated large tumor-specific deposits of IgG and complement in PTC tissue and isolated a putative target antigen. This investigation examines the presence of autoantibodies to cytokeratin 1, a high m.w. cytokeratin normally expressed only in suprabasal keratinocytes, in the serum and tumor tissue of PTC patients. Using immunoprecipitation and Western blot, cytokeratin 1-reactive autoantibodies were demonstrated in 80% of the PTC sera tested, and tumor-derived antibodies were shown to precipitate cytokeratin 1. Using immunohistochemistry, cytokeratins 1 and 10 were found in a large proportion of PTC tumors (39/44) but were absent from normal thyrocytes of most PTC-bearing glands. Our results indicate that this protein is expressed aberrantly in neoplastic cells and is immunogenic in this context.

Topics: Autoantibodies; Autoantigens; Biomarkers, Tumor; Blotting, Western; Carcinoma, Papillary; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Humans; Immunity, Cellular; Immunohistochemistry; Keratins; Thyroid Neoplasms

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

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

Bellini duct carcinoma (BDC) is a rare and highly aggressive renal tumor whose histogenesis is still a matter of debate although a putative origin from collecting ducts has been proposed.. A primary tumor cell culture was obtained from a BDC of a 57-year-old man who presented with a mass of the right kidney. The patient died from disease progression 18 months after diagnosis. The light and ultrastructural features were consistent with previous reports on BDC. The expression of low (Ker 18) and high (Ker 5, Ker 8, Ker 10) molecular weight keratins was studied.. The BDC tumor cells displayed strong positivity for keratins, 5, 8 and 18 but did not react with the anti-keratin 10 antibody. Northern blot analysis of total mRNA revealed expression of the c-erbB-1 oncogene unlike two conventional clear cell carcinomas of the kidney used as control. Cytogenetic analysis revealed an aneuploid karyotype: 53,XY,del(1)(p34),+iso(1q),+iso(5p),+4,+7,+8,-14,del(16)(q22). No submicroscopic deletion on p14-21 and p26 regions of the short arm of chromosome 3 was detected on Southern blot analysis.. The absence of structural changes in the short arm of chromosome 3 (usually present in hereditary and sporadic renal cell carcinomas) in the presence of chromosomal abnormalities observed in malignant lesions of urothelial origin confers to BDC a unique genetic profile among papillary tumors of the kidney.

Topics: Carcinoma, Papillary; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 7; ErbB Receptors; Humans; Karyotyping; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Male; Middle Aged; Monosomy; Trisomy

Multinucleate giant cells (MGCs) occur in a variety of inflammatory, hyperplastic, and neoplastic thyroid disorders. They also have been recognized as a feature of papillary thyroid carcinoma (PTC), particularly in fine-needle aspiration biopsies (FNAB). However, the origin of the MGCs and their comparative frequencies in histologic and cytologic preparations have not been established. Therefore, histologic sections from 76 cases of PTC were examined and immunohistochemical analyses for epithelial and histiocytic markers were performed. Giant cells were identified in histologic sections of 35 cases (46%) of PTC. In cytologic preparations, MGCs were identified in 12 of 22 cases (55%). MGCs were present within follicles or adjacent to papillae, and were often associated with resorption of colloid. Immunohistochemical results indicated that MGCs were of histiocytic rather than epithelial origin. Multinucleate giant cells in PTC most likely represent a response to leakage of colloid into the interstitium. Although MGCs have been described most commonly in inflammatory conditions of the thyroid, the results of this study suggest that their presence should prompt a careful appraisal of associated PTC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antichymotrypsin; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy, Needle; Carcinoma, Papillary; Female; Giant Cells; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Muramidase; Thyroglobulin; Thyroid Neoplasms

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

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

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

Monoclonal antibodies to human stratifying keratin (StK), simple keratin (SK), broad spectrum keratin (BSK) and vimentin were applied to 47 canine mammary tumours (three benign hyperplasia, 26 benign mammary tumours, one malignant mixed tumour, two malignant complex tumours, seven lobular carcinomas, three papillary carcinomas and five squamous cell carcinomas). In benign hyperplasia the SK antibody reacted with acinar and duct epithelial cells; the StK and BSK antibodies reacted strongly with duct epithelial cells in the canine mammary tumours expressed mainly keratins of stratified epithelia rather than those of simple epithelia. Myoepithelial cells in complex and mixed tumours can express StK and vimentin. The finding might be helpful in the assessment of complex tumours where stromal reactions may be confused with myoepithelial neoplastic proliferation. Stromal mesenchymal tissues, including precartilage in complex tumours, and clearly differentiated myoepithelial cells always stained positively for vimentin. Occasional carcinoma cells stained positively for vimentin.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Carcinoma, Lobular; Carcinoma, Papillary; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Hyperplasia; Immunohistochemistry; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Vimentin

The morphological, histochemical, and immunohistochemical findings of seven cases of solid cell nests (SCNs) of the thyroid are described. Light microscopy showed two cell types forming the SCNs, which we refer to as "main cells" and "C cells." In all cases "mixed thyroid follicles" (a unique structure lined by follicular epithelium and epidermoidlike cells) were observed in which the histochemical study confirmed the presence of intraluminal acid mucins. Adult adipose tissue and cartilage were found in one case and foci of cartilage were observed in another case in association with the SCN. Immunohistochemical studies showed positivity of "main cells" for carcinoembryonic antigen (CEA), high- and low-molecular weight keratins, neurotensin, and somatostatin. "C cells" were positive for calcitonin, calcitonin gene-related peptide (CGRP), and chromogranin. The two cell types in SCNs were consistently negative for thyroglobulin. Neuron-specific enolase (NSE)-positive cells were found in the vicinity of the SCN. The unusual association of adipose tissue and cartilage as well as the results of the extended immunohistochemical study in this series provides further support to the belief that SCNs and "mixed thyroid follicles" represent remnants of the ultimobranchial body and should be considered normal components of the thyroid gland.

Topics: Adenocarcinoma, Follicular; Adult; Animals; Carcinoma, Papillary; Female; Goiter, Nodular; Humans; Keratins; Male; Middle Aged; Neuropeptides; Thyroid Neoplasms; Ultimobranchial Body

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

Psammoma bodies and small calcifications are frequently seen in a wide variety of tissues. These deposits of calcium salts render tissues difficult to section. Conventional decalcification alters the tissues; consequently it is not advisable to decalcify tissues containing only small calcium deposits. A simple and rapid method to remove small amounts of calcium salts using citric acid alone is described. This method does not alter the antigenic properties of the substances studied.

Topics: Antigens; Calcium; Carcinoma, Papillary; Citrates; Citric Acid; Decalcification Technique; Humans; Keratins; Meningioma; Staining and Labeling; Thyroglobulin; Thyroid Neoplasms

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

Topics: Antigens, Neoplasm; Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Prognosis; Thyroid Neoplasms; Vimentin

Immunoreactivity for epithelial membrane antigen (EMA), cytokeratin, and vimentin was investigated in 15 papillary thyroid carcinomas (PTC) with distant metastases, 25 PTC without distant metastases, and 34 occult PTC without distant metastases that were found incidentally at autopsy.. More than 50% of the tumor cells were positive for EMA in 7 (47%) of 15 PTC with distant metastases, 0 (0%) of 25 PTC without distant metastases, and 1 (3%) of 34 occult PTC. The incidence of EMA positivity in PTC with distant metastases was significantly different from that of both PTC without distant metastases and occult PTC (P < 0.001). Cytokeratin reactivity was similar in the three groups, and almost all PTC stained strongly for cytokeratin. Concerning vimentin positivity, there were no significant differences in three groups; however, PTC with distant metastases tended to stain more weakly or focally than PTC without distant metastases or occult PTC.. These results suggest that EMA reactivity may be a useful factor for anticipating the individual risk of distant metastasis or death from PTC at the time of initial surgical treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Papillary; Cell Membrane; Cytoplasm; Endothelium, Vascular; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Muscle, Smooth, Vascular; Neoplasms, Unknown Primary; Prognosis; Sex Factors; Survival Rate; Thyroid Neoplasms; Vimentin

Bellini duct carcinomas have recently been identified as a new entity in the spectrum of renal cell carcinomas and 10 cases have now been reported. The present paper adds detailed clinical and morphological data on six new cases. In addition, immunohistological and electronmicroscopical results support the origin of these tumours from the renal collecting ducts, especially the papillary ducts (Bellini ducts). A set of immunohistological reactions, including reactions to cytokeratins 13 and 19, vimentin and UEA-1 was found to facilitate the differential diagnosis of Bellini duct carcinomas from other renal cell carcinomas and infiltrating urothelial carcinomas of renal pelvis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Lectins; Male; Middle Aged; Plant Lectins; Vimentin

Five cases of spindle cell squamous carcinoma of the thyroid associated with tall cell papillary carcinoma were examined. The unusual spindle cell squamous carcinoma in these cases resembles those previously described in other sites, including the breast and oropharynx. Three patients demonstrated concurrent spindle cell squamous anaplastic carcinoma and tall cell papillary carcinoma at initial diagnosis, whereas two patients developed concurrent tumor morphologies subsequent to initial diagnoses of only papillary carcinoma. The mean age of the patients was 77 yr, with a female:male ratio of 4:1. Thyroglobulin immunoreactivity was demonstrated in the tall cell papillary component of each case but was absent in both the squamous and spindle cell components. Low molecular weight cytokeratin immunoreactivity was strongly and diffusely present in the tall cell papillary and squamous components, whereas the spindle cell areas demonstrated only focal weak to negative reactivity. Only the squamous cell component demonstrated consistent immunoreactivity with high-molecular-weight keratin antibodies. These unusual tumors have not been previously described in the thyroid, and the association of spindle cell squamous anaplastic carcinoma with tall cell papillary carcinoma in five independent cases may indicate a particular relationship.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Thyroglobulin; Thyroid Neoplasms

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained in the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion; the patient in the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis.

Topics: Adult; Calcitonin; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; von Willebrand Factor

The clinicopathologic features of five cases of verrucous carcinoma of the vulva and their staining pattern with antikeratin monoclonal antibodies AE1 and AE3 were compared with those of conventional squamous cell carcinoma. Two patients had local recurrences but none died of the tumor. AE1 and AE3 antibodies stained the entire epithelial thickness in both verrucous and squamous cell carcinoma, but in the former the positivity was uniform and homogeneous everywhere, while in squamous cell carcinoma the positivity was extremely disorganized and patchy. The pattern of expression of monoclonal antibodies AE1 and AE3 confirms that verrucous carcinoma is an extremely well-differentiated squamous neoplasm in contrast to squamous cell carcinoma, which is heterogeneous from a viewpoint of differentiation.

Topics: Aged; Antibodies, Monoclonal; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Retrospective Studies; Vulvar Neoplasms

Primary papillary serous carcinoma arising from the peritoneal surface (serous surface papillary carcinoma; SSPC) is a distinctive neoplasm with a histomorphologic resemblance to serous ovarian papillary carcinoma (SOPC). To determine if these tumors are similar antigenically, we studied 13 examples of SSPC and 31 of SOPC immunohistochemically. Antibodies to several determinants known to occur in the Müllerian epithelium were employed. Both neoplasms were uniformly positive for cytokeratin and epithelial membrane antigen (EMA); in addition, SSPC and SOPC were similar in quantitative and qualitative reactivity for B72.3 antigen, carcinoembryonic antigen, Leu M1, CA-125 antigen, LN1, LN2, MB2, S100 protein, placental alkaline phosphatase, and amylase. Residual nonneoplastic mesothelium failed to express any of these antigens except for cytokeratin, EMA, and CA-125. The clinical behavior of SSPC was similar to that of high-stage SOPC; all patients with adequate follow-up died of their tumors. These results suggest that SSPC and SOPC are analogous lesions, with respect to their cellular differentiation. Moreover, it would appear that both neoplasms display only a limited immunophenotypic homology to the mesothelium.

Topics: Adult; Aged; Aged, 80 and over; Amylases; Antigens, Neoplasm; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms; Peritoneal Neoplasms; Proteins

Topics: Aged; Carcinoma, Papillary; Hand; Humans; Keratinocytes; Keratins; Male; Neoplasm Recurrence, Local

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

The presence or absence of myoepithelial cells (ME) has been considered as an important feature in the differential diagnosis of benign and malignant papillary lesions of the breast. We evaluated the distribution of myoepithelial cells in formalin-fixed paraffin-embedded tissue sections of 25 papillomas and 18 papillary carcinomas by ABC immunoperoxidase technique with antibodies to muscle actin (HHF-35) and high molecular weight (HMW) keratin (clone 34BE12, cytokeratins 1, 5, 10, and 14; reacting preferentially with ME cells) and an antiserum to S-100 protein. Also included in the study were eight cases of micropapillary ductal carcinoma in situ (DCIS) having a few fibrovascular cores and five peripheral papillomas with accompanying ductal carcinoma in situ or atypical hyperplasia. The antibodies to muscle actin were sensitive and relatively specific for ME cells of the breast and uniformly labeled ME cells in all 25 papillomas. ME cells were absent or extremely sparse in papillary carcinomas. They were present focally in some of the fibrovascular cores of the micropapillary DCIS, and a mixed pattern was observed in peripheral papillomas with areas of carcinoma. HMW keratin was variably expressed in ME cells in most cases with positive internal controls and was present in several normal ductal and papilloma epithelial cells but not in epithelial cells of papillary carcinomas. HMW keratin, although less specific for ME cells, was a useful adjunct because of its reactivity with ME cells as well as hyperplastic epithelial cells in papillomas, which resulted in a combined positive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actins; Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Myoepithelioma; Papilloma; S100 Proteins

The immunohistochemical reactivity on frozen sections of diverse benign and malignant epithelial proliferations of human breast tissue from 156 patients was examined using antibodies to different cytokeratins. Antibodies recognizing cytokeratins 18 and 19 reacted with luminal epithelial cells but not with myoepithelial cells of normal mammary gland, cystic disease, adenosis, papilloma, and fibroadenoma or with a subpopulation of proliferating cells in sclerosing adenosis and epitheliosis. These antibodies reacted with the tumor cells of all in situ and invasive carcinomas. KA1 antibody, which by one- and two-dimensional gel electrophoresis and immunoblotting was shown to bind preferentially to cytokeratin 14 in a complex with cytokeratin 5, reacted with the nonproliferating myoepithelium of normal gland, cystic disease, adenosis, papilloma, fibroadenoma, and in situ carcinoma; it also reacted with a subpopulation of proliferating cells in sclerosing adenosis and epitheliosis (papillomatosis) but was negative with the tumor cells of all preinvasive and most invasive carcinomas. In adenotic and epitheliotic proliferations, groups of cells were identified that reacted strongly with KA1 antibody in addition to antibodies to cytokeratins 18 and 19. The data are discussed with respect to epithelial cell heterogeneity in the breast. We show that by using such antibodies, benign epithelial proliferations are clearly distinguished from carcinomas.

Topics: Adenofibroma; Adult; Aged; Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Middle Aged; Papilloma

Ten cases of extrauterine malignant mixed mesodermal tumors (MMMTs), nine ovarian, and one pelvic, are presented. One patient had a purely epithelial primary ovarian tumor and MMMT in her recurrent tumors. All the other patients had MMMT in their primary and recurrent tumors. Eight patients had heterologous MMMT including cartilage, striated muscle, and adipose tissue in one case. Two patients had homologous MMMT. All cases presented with metastases involving abdominal organs that were either MMMT or epithelial neoplasms and MMMT. Five patients had recurrent tumors, one extensively involving the spleen. In all recurrent tumors, the mesenchymal components were considerably more abundant than in the primary tumors. Immunohistologic studies of intermediate filaments were performed in seven cases, revealing cytokeratin-positive epithelial structures, vimentin-positive mesenchymal (including cartilaginous) structures, as well as coexpression of cytokeratin and vimentin in anaplastic and giant tumor cells in some cases. Some anaplastic spindle cells, which on routine stains were suggestive of stromal cells, stained positive for cytokeratin, thus identifying their epithelial nature. Desmin staining performed in five cases showed positive staining of rhabdomyoblasts in only one case. Myoglobin staining performed in seven cases was positive in four. The histogenesis from primitive müllerian structures and the natural history of these uncommon neoplasms are discussed in light of the pathological and immunohistochemical data presented.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Desmin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Myoglobin; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pelvic Neoplasms; Vimentin

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma of the thyroid occurring in young adults are reported. The tumour is characterized by diffuse involvement of one or both lobes of the thyroid, marked squamous metaplasia, numerous psammoma bodies, extensive interstitial fibrosis and heavy lymphocytic infiltration with formation of germinal centres. Lymphatic and vascular permeation was found in all three cases. An interesting finding was the presence of irregularly disposed thin bundles of smooth muscle within the fibrous stroma, presumably a result of splaying of the smooth muscle of vessel walls by the sclerotic process. The papillary areas of the tumour stained for thyroglobulin and cytokeratin, while the squamous areas stained strongly for cytokeratin but not for thyroglobulin. The tumours were negative for calcitonin and carcinoembryonic antigen, but showed weak staining for S-100 protein. Numerous S-100 positive Langerhans/interdigitating reticulum cells were scattered within the tumour islands and the lymphoid infiltrate, suggesting an immunological reaction mediated by these antigen-presenting cells.

Topics: Adult; Age Factors; Carcinoma, Papillary; Female; Humans; Keratins; Male; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

Follicular, papillary, anaplastic and medullary cancers of the thyroid were investigated using immunohistochemical methods. The following antibodies were used: anti-S-100, antineuron-specific enolase (NSE), antikeratin, antithyroglobulin, anticalcitonin, anticarcinoembryonic antigen (CEA), antiepithelial membrane antigen (EMA); the following hormones were also tested in the medullary carcinoma: gastrin, ACTH and serotonin. Papillary and follicular carcinoma in particular reacted with anti-S-100 and anti-NSE; the anaplastic neoplasia reacted with anti-S-100 (25%), anti-NSE (12%), antikeratin (12%), antithyroglobulin (12%), anti-CEA (37%) and anti-EMA (37%). Medullary carcinoma reacted with anticalcitonin (100%), anti-CEA (96%), anti-NSE (79%), anti-EMA (4%) and anti-S-100 (17%). We were not able to correlate the virulence of the medullary carcinoma with the anticalcitonin and anti-CEA reactivity, while the hyperplastic C cells were immunoreactive both with calcitonin or with CEA.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; S100 Proteins; Thyroid Neoplasms

The thyroids from 101 consecutive autopsies from Finland were subserially sectioned at 2- to 3-mm intervals. From 36 thyroids, 52 foci of occult papillary carcinoma (OPC) were found, giving a prevalence rate of 35.6%, the highest reported rate in the world. The rate was higher, although not significantly, in males (43.3%) than in females (27.1%), but it did not correlate to the age of the patients. Twenty-six glands contained one tumor focus and ten glands contained two to five tumor foci. Only a minority of the smallest tumors can be detected with the method used. The probable number of OPCs over 0.15 mm in diameter was calculated to be about 300 in this material. The tumor diameter varied from 0.15 mm to 14.0 mm, with 67% of tumors under 1.0 mm. The smallest tumors were usually circumscribed and were composed almost solely of follicles. Larger tumors had more papillary structures and were often invasive. Fibrosis and, in the largest OPCs, lymphocytic reaction were seen around the invasive islands. All tumors were positively stained for thyroglobulin and all but one of the tumors stained positively for epidermal keratin. OPC appears to arise from follicular cells of normal follicles. Apparently the great majority of the tumors remain small and circumscribed and even from those few tumors that grow larger and become invasive OPCs only a minimal proportion will ever become a clinical carcinoma. According to the study, OPC can be regarded as a normal finding which should not be treated when incidentally found. In order to avoid unnecessary operations it is suggested that incidentally found small OPCs (less than 5 mm in diameter) were called occult papillary tumor instead of carcinoma.

Topics: Adolescent; Adult; Aged; Carcinoma, Papillary; Child; Child, Preschool; Cross-Sectional Studies; Female; Finland; Humans; Infant; Keratins; Male; Middle Aged; Neoplasms, Multiple Primary; Thyroid Gland; Thyroid Neoplasms

Seventy cases of anaplastic thyroid carcinomas studied at the Universities of Florence (Italy) and Minnesota are presented. Three morphologic patterns were seen: spindle, giant cell, and squamoid, sometimes in combination. Ultrastructurally, evidence of epithelial differentiation was seen in most but not all cases studied. Immunohistochemically, a stain for cytokeratin using a monoclonal antibody was found the most useful adjunct to diagnosis. Unexpected positivity for carcinoembryonic antigen (CEA) was found in several squamoid tumors. The alleged frequent positivity of this tumor type for thyroglobulin and calcitonin was not confirmed. A third of the tumors were associated with a better differentiated component, of which, presumably, they represented a dedifferentiation. The extremely aggressive behavior of anaplastic thyroid carcinomas was confirmed amply in this series: all of the patients in whom follow-up information was available died of their tumor. Small cell tumors should not be included into the anaplastic category, since they invariably belong to other groups, i.e., malignant lymphoma, medullary carcinoma, and poorly differentiated ("insular") carcinoma.

Topics: Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Papillary; Combined Modality Therapy; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Palliative Care; Sarcoma; Staining and Labeling; Thyroglobulin; Thyroid Neoplasms

Seventeen cases of verrucous carcinoma of the oral cavity were reviewed. It was found that cytologic features generally associated with viral modification were observed in 15 of these cases. This finding suggests that viruses may play some role in the pathogenesis of verrucous carcinoma. The hypothesis that an opportunistic, persistent virus may act in concert with frank carcinogens to promote the development of verrucous carcinoma is discussed.

Topics: Adult; Aged; Animals; Carcinoma, Papillary; Cell Nucleus; Cell Transformation, Neoplastic; Cell Transformation, Viral; Epithelium; Female; Humans; Hyperplasia; Keratins; Male; Middle Aged; Mouth Neoplasms; Tumor Virus Infections

Topics: Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Papillary; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Middle Aged; Ovarian Neoplasms; Ovary

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Chronic Disease; Epithelium; Fluorescent Antibody Technique; Goiter, Nodular; Humans; Intermediate Filament Proteins; Keratins; Lymphoma; Protein Precursors; Sarcoma; Thyroid Gland; Thyroid Neoplasms; Thyroiditis; Vimentin

56 thyroid gland tumours and non neoplastic alterations were studied for keratin and thyroglobulin staining, using the indirect immunoperoxidase method on serial formalin fixed paraffin embedded sections. Papillary carcinomas showed a strong reaction with anti-keratin serum but a weak reaction with anti-thyroglobulin serum. Follicular adenomas and carcinomas showed virtually no reaction for keratin but a strong reaction for thyroglobulin. Undifferentiated and medullary carcinomas did not react with either antiserum, except for single cells in two undifferentiated carcinomas which reacted with anti-keratin serum. In nodular goiters, hyperplastic follicles showed little or no reaction with anti-keratin serum and strong reaction with anti-thyroglobulin serum. It is suggested that this virtually type-specific staining for keratin or thyroglobulin may be related to different degrees of cellular differentiation and organelle content in the tumour cells.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Diagnosis, Differential; Goiter, Nodular; Graves Disease; Histocytochemistry; Humans; Immune Sera; Immunochemistry; Keratins; Thyroglobulin; Thyroid Diseases; Thyroid Neoplasms; Thyroiditis

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Urinary Bladder Neoplasms