Clear Cell Papillary Renal Cell Tumor Revisited

Clear cell papillary renal cell tumor (CCPRCT), formerly known as clear cell papillary renal cell carcinoma, is a low-grade renal neoplasm characterized by cytokeratin 7 and cup-like carbonic anhydrase 9 immunopositivity and absence of von Hippel-Lindau (VHL) abnormalities. Given the prognostic differences, distinguishing CCPRCT from clear cell renal cell carcinoma (CCRCC) is clinically important. However, some tumors diagnosed morphologically and immunohistochemically as CCPRCT have been found to harbor VHL abnormalities, which complicates clinical management. This study aimed to clarify how clinical, histologic, and immunohistochemical characteristics varied based on VHL status. Among 17 CCPRCTs analyzed, VHL abnormalities were identified in 10 (58.8%) cases, including VHL mutations in 6 cases and 3p loss of heterozygosity in 7 cases. Tumors were stratified into 3 groups based on VHL allele status: 3 cases with biallelic VHL inactivation (CCPRCT-biVHL), 7 with monoallelic VHL inactivation (CCPRCT-monoVHL), and 7 with wild-type VHL (CCPRCT-wtVHL). We integrated the molecular with morphologic and immunohistochemical findings, and reclassified 17 cases into 5 CCRCCs mimicking CCPRCT, 5 CCPRCTs-monoVHL, and 7 CCPRCTs-wtVHL cases. All tumors exhibited favorable clinical courses, with no instances of metastasis or recurrence. No significant differences in clinical, pathologic, or immunohistochemical features were observed among the 3 groups or between CCRCCs mimicking CCPRCT and CCPRCTs. This study demonstrated that strict morphologic and immunohistochemical criteria can distinguish most CCRCCs mimicking CCPRCT from CCPRCT. The diagnosis of CCPRCT should be expanded to include tumors with monoallelic VHL alteration exhibiting typical morphologic and immunohistochemical features.