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1/21. Differential diagnosis between monomorphic clear cell adenocarcinoma of salivary glands and renal (clear) cell carcinoma.

    Clear cell adenocarcinoma of salivary glands (CCASG) is a relatively rare tumor, composed entirely of clear cells of putative ductal origin. It bears striking morphologic similarities to renal cell carcinoma (RCC) of clear cell type on hematoxylin and eosin stains. Differentiation between CCASG and metastatic RCC to the salivary glands has been considered problematic or even impossible on morphologic grounds. We examined three cases of CCASG and 12 cases of RCC (6 primary and 6 metastatic) by hematoxylin and eosin staining, immunohistochemistry, and electron microscopy. Two distinctive immunohistochemical and ultrastructural patterns emerged from this analysis. CCASG showed positivity for high molecular weight cytokeratin and carcinoembryonic antigen and ultrastructurally showed prominent squamoid differentiation, glycogen pools, and absence of lipid. In contrast, RCC was characterized by positivity for vimentin and complete absence of staining for high molecular weight cytokeratin and carcinoembryonic antigen. On ultrastructural studies, RCC lacked any squamoid differentiation, and the tumor cells contained abundant cytoplasmic lipid in addition to glycogen. Thus, based on the consistent differences on the immunohistochemical staining patterns and their characteristic subcellular morphology, CCASG and RCC can be distinguished on pathologic evaluation. The different direction of differentiation of the cells in CCASG and RCC (i.e., ductal in the former and renal tubular and mesodermal in the latter) results in their distinctive immunophenotypical and ultrastructural features.
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2/21. HMB-45/melan-A and smooth muscle actin-positive clear-cell epithelioid tumor arising in the ligamentum teres hepatis: additional example of clear cell 'sugar' tumors.

    HMB-45-positive clear-cell epithelioid tumor arising in the ligamentum teres hepatis of a 13-year-old Japanese girl is described. The well-defined tumor was completely removed and measured 9 x 7 x 6 cm. Cut sections showed a tan-white, homogeneous appearances with no hemorrhage or necrosis. The tumor was composed of nests or sheets of polygonal or oval-shaped cells rich in clear or finely granular cytoplasm. Capillary network was well developed, and sinusoid vessels were often seen with occasional perivascular hyalinization. There was moderate nuclear atypia but mitotic figures were absent. periodic acid-Schiff stain showed a large amount of glycogen digested by diastase. Immunohistochemical stains for smooth muscle actin, Melan-A, and HMB-45 were positive in most of the tumor cells. Stains for vimentin, muscle actin, and HAM56 were focally positive, whereas stains for desmin, cytokeratin, epithelial membrane antigen, S-100, CD34, CD68, CD99, neurofilament proteins, and estrogen/progesterone receptors were negative. Ultrastructurally, the cytoplasm contained a considerable number of mitochondria, monoparticipate or membrane-bound glycogen, and longitudinally oriented thin filaments with focal condensations and subplasmalemmal densities. The histopathology of the present case, originally interpreted as epithelioid leiomyoma, was consistent with clear cell "sugar" tumors. The present case may indicate ubiquitous distribution of clear cell "sugar tumors" of which histogenesis remains unknown but is presumed to be of perivascular epithelioid cell origin.
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3/21. Tubulocystic clear cell adenocarcinoma arising within the prostate.

    neoplasms resembling ovarian common epithelial-type tumors, including clear cell adenocarcinomas, rarely occur in the lower urinary tract of men. When they do, they develop in the urethra or urinary bladder. We report a case of such a tumor arising within the prostate of a 47-year-old man. The tumor was a cystic mass in the left posterolateral region of the prostate. Histologically, the tumor was chiefly composed of tubulocystic and papillary glands lined by glycogen-rich, cuboidal or hobnail cells with clear to eosinophilic cytoplasm. The tumor cells were strongly positive for pan-cytokeratin, low molecular weight cytokeratin, and epithelial membrane antigen, and focally positive for high molecular weight keratin. The tumor did not immunohistochemically express prostate-specific antigen (PSA) and prostatic acid phosphatase. Serologically, the patient had increased levels of CA125 instead of PSA. The clinical as well as the pathologic features are consistent with a clear cell adenocarcinoma as seen in the female genital tract rather than a typical prostatic adenocarcinoma.
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4/21. Clear-cell odontogenic carcinoma with pulmonary metastases resembling pulmonary meningothelial-like nodules.

    Clear-cell odontogenic carcinoma (CCOC) is a rare neoplasm with malignant potential and unknown cytogenetic alterations. We describe the case of a 43-year-old woman who presented with an unusual odontogenic epithelial tumor. Histologically, the tumor was composed of clear-cell areas and exhibited a squamous pattern with little nuclear pleomorphism similar to benign squamous odontogenic tumor. Multiple small pulmonary nodules occurring 3 years after primary surgical treatment histologically closely resembled benign minute pulmonary meningothelial-like nodules (MPMN) with clear-cell features. comparative genomic hybridization (CGH) and immunohistochemistry, performed as diagnostic adjuncts, revealed in the odontogenic tumor and the pulmonary lesions a very similar pattern of chromosomal aberrations (loss of 9, gains of 14q, 19 and 20 in both, and additional loss of 6 in the odontogenic tumor) and the same pattern of expression (positive for cytokeratin 5, 6, 8, 19 and negative for cytokeratin 18, epithelial membrane antigen, and vimentin), differing from that of MPMN. These findings confirmed the final diagnosis of metastasizing CCOC with partial squamous differentiation, substantiated the unfavorable prognosis of the clear-cell component, and highlighted the diagnostic impact of CGH and immunohistochemistry for classification of these morphologically peculiar pulmonary CCOC metastases.
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5/21. Clear cell carcinoma of the breast with solid papillary pattern: a case report with immunohistochemical profile.

    glycogen rich clear cell carcinoma of the breast is a rare neoplasm with different morphological characteristics to ordinary breast carcinomas. However, it has some common features with clear cell carcinomas of other organs. This report describes a case of clear cell carcinoma of the breast with a solid papillary pattern centrally localised in the left breast of a 45 year old woman. antibodies directed against cytokeratin 7 (CK7), CK10, CK14, CK17, CK18, CK19, CK20, CK5/6/18, CK8/18, high molecular weight cytokeratin AE3, high molecular weight cytokeratin 34betaE12, the oestrogen receptor, the progesterone receptor, chromogranin, S-100 protein, smooth muscle actin, vimentin, and carcinoembryogenic antigen were applied to analyse the immunophenotypical profile of this rare neoplasm.
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6/21. Clear cell (glycogen-rich) gastric adenocarcinoma.

    Clear cells have been described in many tumors of varying differentiation. Although clear cell carcinoma is well-recognized in the lower urinary and female genital tracts, its occurrence in the gastrointestinal tract and related structures is uncommon. There have been only a few case reports and small series reporting this morphologic phenomenon in the stomach, colon, and biliary tract. Clear cell carcinoma of the endometrium has been associated with poor prognosis, but the prognostic significance of clear cells in gastric adenocarcinoma is unknown. Herein we describe three cases of clear cell, glycogen-rich, gastric adenocarcinoma and evaluate the frequently used classification systems for gastric cancer. Two tumors showed a tubulopapillary pattern and one showed a predominantly diffuse sheet-like growth. The proliferation (MIB) index in all cases was approximately 20%. Only case 1 showed focal staining for alpha-fetoprotein and both cases 1 and 2 showed focal carcinoembryonic antigen reactivity. In conclusion, we describe three cases of clear cell gastric carcinoma that presented as high-stage disease.
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7/21. Clear cell carcinoma of the pancreas: an adenocarcinoma with unusual phenotype of duct cell origin.

    Although clear cell carcinoma has been found in various organs, only six cases have been reported in the pancreas. Moreover, the histogenesis of clear cell carcinoma of the pancreas remains controversial. We report a case of clear cell carcinoma of the pancreas in a 61-year-old woman, with an unusual pheno- or genotype detected by histochemical, immunohistochemical, and K- ras oncogene analyses. Histologically, the pancreatic tumor was predominantly composed of clear cell nests with scanty fibrous stroma and scattered duct-like structures. Neither clear cell nor duct-like components of the tumor showed mucin production. Immunohistochemical analysis of neoplastic cells showed a positive reaction to antibodies against cytokeratins 8 and 19, carbohydrate antigen 19-9, and alpha-1-antitrypsin, and showed no reaction to antibodies against carcinoembryonic antigen, neuroendocrine markers, trypsin, amylase, and HMB45. K- ras analysis revealed no mutation at codon 12 in either clear cell or duct-like components. The patient has had no recurrence as yet. The pancreatic carcinoma in our patient may be of duct cell origin, but the results of histochemical, immunohistochemical, and gene analyses and patient's outcome were unusual compared with those of previous cases.
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8/21. Clear cell ductal adenocarcinoma of pancreas: a case report and review of the literature.

    We present a unique carcinoma of the pancreas with predominantly clear cell morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin. Immunohistochemically, the cells were positive for the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen. Stains for the neuroendocrine markers synaptophysin and chromogranin were negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional outstanding feature was the presence of dense intraluminal and intracytoplasmic hyaline globules, which were immunohistochemically positive for alpha1-antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon 12, providing molecular evidence of ductal origin. In the proper morphologic context supported by immunohistochemistry, clear cell carcinoma can be regarded as a rare variant of ductal adenocarcinoma.
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9/21. Clear cell adenocarcinoma of the tongue.

    A firm, ulcerated tumor formed on the left side of the tongue of an elderly woman. Histopathological analysis showed that this unusual neoplasm was composed of monomorphic polygonal cells that exhibited a clear cytoplasm containing large amounts of periodic acid Schiff (PAS)-positive, diastase-digestive material. Most of the tumor cells stained immunohistochemically for Cytokeratin, high-molecular, CAM5.2, and epithelial membrane antigen (EMA), but were negative for alpha-smooth muscle actin, vimentin, glial fibrillary acid protein (GFAP), and S-100 protein. These findings supported a diagnosis of clear cell adenocarcinoma. Although patients with this type of tumor generally have a favorable prognosis, the tumor in our patient was fast-growing and contained a large number of Ki-67 positive cells, which are known to be highly proliferative. Thus, this case highlights the fact that even clear cell adenocarcinomas that are usually slow-growing should be investigated by conventional morphological techniques and their proliferative activity quantified in order to select the most appropriate treatment strategy.
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10/21. Clear cell renal cell carcinoma with syncytial giant cells: a case report and review of the literature.

    Renal cell carcinoma with syncytial giant cells (SGCs) is rare; to our knowledge, there are only 3 cases reported in the English literature. We report on a case that, unlike previous reports, was associated with higher grade renal cell carcinoma and an aggressive behavior. A 63-year-old man with gross hematuria was found to have a large left renal mass and no evidence of metastasis. The nephrectomy specimen contained a 14.8-cm mass that was confined within the renal capsule. Microscopically, a 1.8-cm area of SGCs was noted in a background of clear cell renal cell carcinoma of Fuhrman nuclear grades 2 to 4. The SGCs had voluminous cytoplasm, multiple large nuclei with prominent nucleoli, and focal emperipolesis. Identical to the background mononuclear tumor cells, the SGCs were positive for AE1/AE3, vimentin, and epithelial membrane antigen and negative for CD68, beta-human chorionic gonadotropin, and mucin. Three months after surgery, the patient developed metastases in the liver, right kidney, and lungs.
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