Small papillary renal neoplasm with reverse polarity (≤ 15 mm) may challenge the current diagnostic criteria of papillary adenoma.

Papillary renal neoplasm with reverse polarity (PRNRP), currently categorized as a papillary renal cell carcinoma (RCC) variant in the 5th edition of the WHO Classification, has shown increasing evidence of clinicopathological and molecular distinctions from conventional papillary RCC. Therefore, PRNRP should be separated from papillary RCC. Our analysis of 35 PRNRP cases with a mean tumor size of 15.0 mm demonstrated clinicopathological features consistent with prior reports. Uniform histological findings showed tumors with abundant eosinophilic cytoplasm and apically oriented low-grade nuclei, complemented by a consistent immunohistochemical profile of keratin 7 positivity and GATA3 expression. AMACR and vimentin expression were frequently negative. Fluorescence in situ hybridization detected abnormalities in chromosomes 7/17/Y in 4 cases. KRAS mutations were identified in 23 cases. Novel observations included that cystic architecture was more frequently observed in tumors exceeding 15 mm compared to their smaller counterparts (≤ 15 mm). Fifteen ≤ 15 mm PRNRP cases demonstrated an absence of fibrous capsule, meeting diagnostic criteria for papillary adenoma. However, comparative analysis of 45 papillary adenoma cases revealed distinct clinicopathological differences from PRNRP. These findings reinforce current proposals for distinguishing PRNRP from conventional papillary RCC. Furthermore, our data highlight a diagnostic conundrum regarding small (≤ 15 mm) PRNRP cases lacking fibrous capsules, which challenge current diagnostic boundaries between PRNRP and papillary adenoma. Future classification should address both the separation from papillary RCC and the need to refine the diagnostic criteria of papillary adenoma.