Recurrent KRAS mutations are early events in the development of papillary renal neoplasm with reverse polarity

Autor: Khaleel I. Al-Obaidy, Rola M. Saleeb, Kiril Trpkov, Sean R. Williamson, Ankur R. Sangoi, Mehdi Nassiri, Ondrej Hes, Rodolfo Montironi, Alessia Cimadamore, Andres M. Acosta, Zainab I. Alruwaii, Ahmad Alkashash, Oudai Hassan, Nilesh Gupta, Adeboye O. Osunkoya, Joyashree D. Sen, Lee Ann Baldrige, Wael A. Sakr, Muhammad T. Idrees, John N. Eble, David J. Grignon, Liang Cheng
Rok vydání: 2022
Předmět:
Zdroj: Modern Pathology. 35:1279-1286
ISSN: 0893-3952
DOI: 10.1038/s41379-022-01018-6
Popis: We evaluated the clinicopathologic and molecular characteristics of mostly incidentally detected, small, papillary renal neoplasms with reverse polarity (PRNRP). The cohort comprised 50 PRNRP from 46 patients, divided into 2 groups. The clinically undetected (5 mm) neoplasms (n = 34; 68%) had a median size of 1.1 mm (range 0.2-4.3 mm; mean 1.4 mm), and the clinically detected (≥5 mm) neoplasms (n = 16; 32%) which had a median size of 13 mm (range 9-30 mm; mean 16 mm). Neoplasms were positive for GATA3 (n = 47; 100%) and L1CAM (n = 34/38; 89%) and were negative for vimentin (n = 0/44; 0%) and, to a lesser extent, AMACR [(n = 12/46; 26%; weak = 9, weak/moderate = 3)]. KRAS mutations were found in 44% (n = 15/34) of the clinically undetected PRNRP and 88% of the clinically detected PRNRP (n = 14/16). The two clinically detected PRNRP with wild-type KRAS gene were markedly cystic and contained microscopic intracystic tumors. In the clinically undetected PRNRP, the detected KRAS mutations rate was higher in those measuring ≥1 mm vs1 mm [n = 14/19 (74%) vs n = 1/15 (7%)]. Overall, the KRAS mutations were present in exon 2-codon 12: c.35 G T (n = 21), c.34 G T (n = 3), c.35 G A (n = 2), c.34 G C (n = 2) resulting in p.Gly12Val, p. Gly12Asp, p.Gly12Cys and p.Gly12Arg, respectively. One PRNRP had a G12A/V/D complex mutation. Twenty-six PRNRP were concurrently present with other tumors of different histologic subtypes in the ipsilateral kidney; molecular testing of 8 of the latter showed wild-type KRAS gene despite the presence of KRAS mutations in 5 concurrent PRNRP. On follow up, no adverse pathologic events were seen (range 1-160 months; mean 44 months). In conclusion, the presence of KRAS mutations in small, clinically undetected PRNRP provides a unique finding to this entity and supports its being an early event in the development of these neoplasms.
Databáze: OpenAIRE
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