Papillary Renal Neoplasm With Reverse Polarity Is Often Cystic

Abstract

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly proposed entity with distinct histology and frequent KRAS mutations. To date, 93 cases of PRNRPs have been reported. In this study, we present 7 new cases of PRNRP and review the literature. Most of the pathologic features in our 7 cases are similar to those previously reported cases. However, all 7 of our cases showed at least partial cystic changes, which was not stressed in prior studies. Single-nucleotide polymorphism-microarray based chromosomal analysis demonstrated no trisomy or other alteration of chromosomes 7 or 17; and no loss or other alteration of chromosome Y was detected in all 7 cases. Next-generation sequencing detected KRAS missense mutations in 4 of 7 cases. No fusion genes were detected. In summary, PRNRP is a small, well-circumscribed often encapsulated and cystic neoplasm with loose papillary formations. Cuboidal tumor cells always have eosinophilic cytoplasm and nuclei located at the pole opposite the basement membrane with a low World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) nuclear grade. The fibrovascular cores can be hyalinized or edematous. Macrophage aggregates and intracellular hemosiderin are uncommon, and no psammoma bodies or necrosis should be seen. Immunophenotypically, this tumor is always positive for CK7 and GATA3, and negative for CD117 and vimentin. CD10 and AMACR can be positive, but often weakly and focally. PRNRP often has KRAS mutations, however, only 32% of cases have chromosomal abnormalities in chromosomes 7, 17, and Y. No recurrences, metastases, or tumor-related deaths have been reported following complete resection.

Rare papillary renal neoplasm with reverse polarity: A case report and review of the literature

“…Recent studies have shown that PRNRP has high-frequency KRAS gene mutations; the KRAS mutation rate was found in 85% of the tested cases, and KRAS gene mutations in PRNRP were concentrated in the exon 2 codon 12 (3,10). Among them, the G12 V missense mutation was the hotspot mutation (mutation rate was 33.3%-75.0%), followed by G12D (0-30.7%), G12R (3.8%-25.0%) and G12C (0-11.1%), the BRAF V600R mutation was detected in one KRAS wild-type case (3,5,17).…”

“…Among them, the G12 V missense mutation was the hotspot mutation (mutation rate was 33.3%-75.0%), followed by G12D (0-30.7%), G12R (3.8%-25.0%) and G12C (0-11.1%), the BRAF V600R mutation was detected in one KRAS wild-type case (3,5,17). Fluorescence in situ hybridization (FISH) analysis showed that 32% (14/44) of papillary renal tumours with reverse polarity had abnormalities in chromosomes 7 and 17, and only 2 cases (2/44) had chromosome Y deletion (10), which further proved that it was similar but not identical to classic PRCC. In this study, because the patient refused to undergo molecular genetic testing, we could not further understand whether the patient had gene mutations and chromosomal variations.…”

Papillary renal cell carcinoma: current and controversial issues

“…Another recently described emerging entity is papillary renal neoplasm with reversed polarity [56]. Tumours are usually small and can be partly cystic [57]. They have a quite characteristic morphology, recapitulated in several recent publications [56,[58][59][60][61][62][63], composed of thin papillae with hyalinised cores filled with a single row of eosinophilic cells with small uniform nuclei (sometimes with optical clearing) aligned and pushed against the apical pole (reversed polarity), frequently with peritumoral lymphoid aggregation.…”

Papillary Renal Cell Carcinoma: Evolving Classification by Combined Morphologic and Molecular Means

“…Several other investigators have further confirmed the small mean size, low stage, and indolent behavior of PRNRP. 54,55,[58][59][60][61] Later, Al-Obaidy and colleagues demonstrated by targeted next-generation sequencing that KRAS mutations occur as a consistent finding in PRNRP, in contrast to a comparison group of 30 PRCCs in which no KRAS mutations were detected. 62 This unique genetic finding was subsequently confirmed by several other studies.…”