Recurrent kras mutation is an early event in the development of papillary renal neoplasm with reverse polarity
Al-Obaidy K, Eble J, Cheng L, Nassiri M, Williamson S, Idrees M, and Grignon D. Recurrent kras mutation is an early event in the development of papillary renal neoplasm with reverse polarity. Modern Pathology 2020; 33(3):846.
Background: Papillary renal neoplasm with reverse polarity is a recently proposed distinct renal tumor. In addition to its unique morphologic and immunohistochemical features, a recent study showed that these tumors represent the only kidney tumor with recurrent KRAS mutation. Design: We reviewed a series of 177 previously retrieved cases of end stage kidneys at Indiana University for incidentally found non-mass forming papillary renal neoplasms with reverse polarity, using the same criteria suggested by Al-Obaidy et al. The tumors were composed of papillary or tubulopapillary architecture covered by a single layer of eosinophilic cells with finely granular eosinophilic cytoplasm and apically located round nuclei with inconspicuous nucleoli. No intracellular hemosiderin, psammoma bodies, mitotic figures, necrosis, or clusters of foamy macrophages should be present. Immunohistochemical staining (GATA-3, AMACR and vimentin) and polymerase chain reaction (PCR) for KRAS mutations was performed. Results: The cohort consisted of 8 cases from 7 patients, 4 were males and 4 were females, with an age range of 42-75 years (mean, 57 years, median 60 years) and a size range of 1-3 mm. All cases were positive for GATA-3 immunostain. AMACR and vimentin immunostains were performed on one and both were negative (Figure 1). Of the 8 cases identified, only 3 had successful PCR analysis (neoplasm sizes 3 mm). These were identified in 2 patients (one with bilateral neoplasms). KRAS mutations were present in all 3 neoplasms and were clustered in exon 2-codon 12: C.35 G>T (n = 2) or c.34 G>T (n = 1) resulting in p.Gly12Val and p.Gly12Cys alterations, respectively. An attempt to analyze the remaining 5 cases failed to detect any mutations, most likely due to the small size (1 mm), and a high likelihood of tissue loss with deeper sectioning despite microdissection attempts. One lesion with a KRAS mutation had an associated acquired cystic diseases associated renal cell carcinoma; that was negative for KRAS mutation. (Figure presented) Conclusions: The presence of KRAS mutations in small, clinically undetectable lesions provides a unique supportive finding to this proposed entity. In contrast to the size criteria used to define the clinical course of papillary adenoma vs carcinoma, the terminology "papillary renal neoplasms with reverse polarity" is recommended for all lesions identified regardless of the size as this study finds KRAS mutation to be an early event in their pathogenesis.