Papillary renal neoplasm with reverse polarity shows benign behavior: Results from a 77-case clinicopathological and molecular study.

Abstract

Papillary renal neoplasm with reverse polarity (PRNRP) is a low-grade renal tumor characterized by oncocytic cells with apical nuclei, GATA3 expression, and frequent KRAS mutations. This study aimed to comprehensively characterize and determine prognostic significance of PRNRP by conducting clinical, histological, immunohistochemical, and genetic analyses while reviewing prior reports. A total of 506 patients with papillary renal cell carcinoma (PRCC) who underwent curative nephrectomy from 1989 to 2023 were analyzed, leading to the reclassification of 77 cases (17 %) as PRNRP. All cases were pT1 tumors with a median size of 1.5 cm. Initially, 40 %, 31 %, and 18 % were diagnosed as PRCC type 1, PRNRP, and PRCC type 2, respectively. PRNRP cases consistently displayed characteristic features; however, two tumors exhibited high-grade nuclear atypia resembling WHO/ISUP grade 3, highlighting the existence of atypical subgroups. Immunohistochemical analysis showed GATA3 expression in 97 % of cases. Transcription factor EB (TFEB) expression was observed in 86 % of cases. KRAS exon 2 mutations were identified in all cases, including the two atypical PRNRPs. Neither recurrence nor disease-specific death occurred throughout a median follow-up period of 46 months. This study highlights the necessity of thorough diagnostic evaluation, incorporating unique histological features, GATA3 positivity, and KRAS mutation analysis, especially in the presence of atypical morphology, while reaffirming the benign nature of PRNRP.