Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis.

BACKGROUND

Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC).

METHODS

We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade.

RESULTS

All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting resultsAmong the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored  mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected  mutations; two (33%) harbored pathogenic mutations in the  or the  genes; and one (16%) was wild type.

CONCLUSION

We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least  mutations.