Morphological, immunohistochemical, and genomic analyses of papillary renal neoplasm with reverse polarity.

Abstract Papillary renal neoplasm with reverse polarity (PRNRP) is a recently proposed entity of renal tumor. It shows a far better prognosis than papillary renal cell carcinoma (PRCC) and frequently has KRAS missense mutation. In this study, we compared 14 cases of PRNRP and 10 cases of PRCC type 1 (PRCC1) and type 2 (PRCC2) from clinical, morphological, immunohistochemical, and molecular biological perspectives. We subjected all PRNRP and PRCC cases to immunohistochemical analysis. Whole-exome sequencing using next-generation sequencing (NGS) was performed for six cases of PRNRP, three cases of PRCC1, and four cases of PRCC2. A search for KRAS gene mutation in the remaining eight cases of PRNRP was performed by polymerase chain reaction (PCR) sequencing. The results showed that all cases of PRNRP were pT1N0M0, none of which followed a course of recurrence or tumor-related death. Immunohistochemical analysis revealed diffuse staining of CK7, EMA, PAX8, and GATA3, but weak or negative staining of CD10, CD15, and AMACR in PRNRP. By NGS and PCR, KRAS missense mutation was detected in 11 of 14 PRNRP cases, although pathogenic KRAS mutation was not observed in PRCC1 and PRCC2. NGS analysis revealed less tumor mutation burden in PRNRP than in PRCC. PRNRP also showed no specific chromosomal copy number abnormalities including gains of 7 and 17. In conclusion, we propose that PRNRP is a distinct condition from papillary renal cell carcinoma.