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Clear cell papillary renal cell carcinoma: a distinct histopathologic and molecular genetic entity.

A group of renal tumors composed mainly of cells with clear cytoplasm arranged in papillary patterns and arising in end-stage kidneys has recently been identified. The aim of our study is to investigate the cytogenetic and immunohistochemical phenotypes of these unusual renal tumors, and of morphologically similar tumors arising in kidneys unaffected by end-stage renal disease. Seven tumors from 5 patients (age range: 53 to 64 y, mean: 60 y; 3 men and 2 women) were identified. Sections were obtained from paraffin blocks, including the tumors and adjacent non-neoplastic renal parenchyma. Interphase fluorescence in situ hybridization was performed with centromeric probes for chromosomes 3, 7, 17, Y, and with a subtelomeric probe for 3p25. Immunohistochemistry was performed with antibodies against cytokeratin 7, carbonic anhydrase IX, alpha-methylacyl-CoA racemase, CD10, and transcription factor E3. Four of the tumors were from patients who did not have end-stage renal disease. One patient had end-stage renal disease and presented with 3 morphologically identical tumors, composed of clear cells arranged in a mixture of cystic and papillary structures. Follow-up data were available from all patients and none showed recurrence or metastasis (mean follow-up: 24 mo). All 7 tumors (ranging from 4 to 50 mm in diameter) were stage pT1. All tumors lacked the gains of chromosome 7 and losses of chromosome Y that are typical of papillary renal cell carcinoma. Only 1 tumor showed gain of chromosome 17. Deletion of 3p, usually seen in clear cell renal cell carcinoma, was not detected. All tumors showed strongly positive immunohistochemical staining for cytokeratin 7 and carbonic anhydrase IX and negative immunostaining with antibodies against alpha-methylacyl-CoA racemase, CD10, and transcription factor E3. In conclusion, clear cell papillary renal cell carcinoma can arise in otherwise normal kidneys and in kidneys with end-stage renal disease. This tumor has immunophenotypic and genetic profiles distinct from those of either classic papillary or clear cell renal cell carcinoma, and should be considered a distinct entity in the spectrum of renal cell neoplasia.

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