Tubulocystic carcinoma of the kidney: clinicopathologic analysis of 31 cases of a distinctive rare subtype of renal cell carcinoma.
ABSTRACT A distinctive tumor described under the terms Bellini duct carcinoma and low-grade collecting duct carcinoma has been referred to by us and others as tubulocystic carcinoma. This renal cell carcinoma subtype is not recognized in the World Health Organization 2004 classification. Herein, we present a detailed study of 31 cases to further characterize this rare subtype of renal cell carcinoma. The tumor occurred in adults (mean age, 54 years) with a strong male predominance (7:1). Grossly, the tumors ranged from 0.7 to 17 cm, and exhibited a spongy or "bubble wrap" appearance reflecting the microscopic presence of variably sized cystically dilated tubules lined by a single layer of epithelium. The lining varied with a cuboidal, flat, and hobnail cell appearance, and the neoplastic cells had abundant eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. The cysts were closely spaced with an intervening variably fibrotic stroma. Immunohistochemistry and ultrastructural examination showed features of proximal convoluted tubules (Pax 2 immunoreactivity and short microvilli with brush border organization) and distal nephron (kidney-specific cadherin immunoreactivity and cytoplasmic interdigitation). Gene expression profiling showed that tubulocystic carcinoma displayed a unique molecular signature. Twenty-four tumors were stage pT1, 4 stage pT2, and 3 stage pT3. Disease progression (median follow-up of 56 months) occurred in 3 patients; 1 with local recurrence, and 2 with distant metastasis to bone and liver. In light of the distinctive clinicopathologic features and a low but definite metastatic potential, this unique subtype of renal cell carcinoma deserves formal recognition in the contemporary classification of renal neoplasms.
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ABSTRACT: Alpha-methyl CoA racemase (AMACR), a new molecular marker for prostate cancer, has been recently reported to be one of the most highly expressed genes in papillary renal cell carcinomas (RCCs). We tested the diagnostic usefulness of AMACR antibody in a series of 110 renal tumors: 53 papillary RCCs (33 type 1, 20 type 2); 25 conventional RCCs; 6 chromophobe RCCs; 9 oncocytomas; 5 mucinous tubular and spindle tumors; 2 urothelial carcinomas; 7 angiomyolipomas; and 2 Bellini carcinomas. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections, with a primary prediluted rabbit monoclonal anti-AMACR antibody. Both type 1 and type 2 papillary RCCs exhibited cytoplasmic immunoreactivity for AMACR, with diffuse strong granular staining in 96.4% (53/55) of tumors, without correlation with type or nuclear grade. The 5 mucinous, tubular, and spindle cell carcinomas strongly expressed AMACR, and only 5 of 25 clear cell RCCs and 1 of 9 oncocytomas were focally reactive. The remaining 6 chromophobe RCCs, 5 urothelial carcinomas, and Bellini duct carcinomas showed no immunoreactivity for AMACR. Because high expression of AMACR is found in papillary RCCs (type 1 and 2) and in mucinous, tubular, and spindle cell carcinomas of the kidney, immunostaining for AMACR should be used in conjunction with other markers when histological typing of a renal tumor is difficult.Human Pathlogy 07/2006; 37(6):698-703. · 2.84 Impact Factor
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ABSTRACT: Renal tumor classification is important because histopathological subtypes are associated with distinct clinical behavior. However, diagnosis is difficult because tumor subtypes have overlapping microscopic characteristics. Therefore, ancillary methods are needed to optimize classification. We used oligonucleotide microarrays to analyze 31 adult renal tumors, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma. Expression profiles correlated with histopathology; unsupervised algorithms clustered 30 of 31 tumors according to appropriate diagnostic subtypes while supervised analyses identified significant, subtype-specific expression markers. Clear cell RCC overexpressed proximal nephron, angiogenic, and immune response genes, chromophobe RCC oncocytoma overexpressed distal nephron and oxidative phosphorylation genes, papillary RCC overexpressed serine protease inhibitors, and extracellular matrix products, and angiomyolipoma overexpressed muscle developmental, lipid biosynthetic, melanocytic, and distinct angiogenic factors. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry of formalin-fixed renal tumors confirmed overexpression of proximal nephron markers (megalin/low-density lipoprotein-related protein 2, alpha-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron markers (beta-defensin 1, claudin 7) in chromophobe RCC/oncocytoma. In summary, renal tumor subtypes were classified by distinct gene expression profiles, illustrating tumor pathobiology and translating into novel molecular bioassays using fixed tissue.Journal of Molecular Diagnostics 06/2005; 7(2):206-18. · 3.95 Impact Factor
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ABSTRACT: The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.American Journal Of Pathology 06/2001; 158(5):1639-51. · 4.52 Impact Factor