Clear cell papillary renal cell carcinoma: a clinicopathological study emphasizing ultrastructural features and cytogenetic heterogeneity

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal neoplasm, which was initially described in end-stage renal disease (ESRD), but some cases have been reported in otherwise normal kidneys. We report a series of 11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was available for 8 patients. No patients developed local recurrence, distant or lymph-node metastasis, or cancer death. Histologically, all tumors exhibit morphologic features typical of CCPRCC including a mixture of cystic and papillary components, covered by small to medium-sized cuboidal cells with abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity for CK7, CA9, Vim, and HIF-1α, coupled with negative reactions for CD10, P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. Ultrastructurally, the tumor cells composed of numerous glycogens with scanty cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome 3) was detected in 3 cases suggesting that at least some of these lesions have demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed of numerous glycogens with scanty cell organelles, reminiscent of CCRCC suggesting the close pathogenesis relationship of CCPRCC with CCRCC.