Chromophobe renal cell carcinoma: Novel molecular insights and clinicopathologic updates

Reza Alaghehbandan; Christopher G Przybycin; Virginie Verkarre; Rohit Mehra

doi:10.1016/j.ajur.2021.11.010

Chromophobe renal cell carcinoma: Novel molecular insights and clinicopathologic updates

Asian J Urol. 2022 Jan;9(1):1-11. doi: 10.1016/j.ajur.2021.11.010. Epub 2021 Dec 1.

Authors

Reza Alaghehbandan¹, Christopher G Przybycin², Virginie Verkarre³, Rohit Mehra^{4

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Affiliations

¹ Department of Pathology, Faculty of Medicine, University of British Columbia, Royal Columbian Hospital, Vancouver, BC, Canada.
² Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
³ Department of Pathology, Georges Pompidou European Hospital, AP-HP, Paris University, INSERM UMR 970, PARCC, Paris, France.
⁴ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵ Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
⁶ Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA.

Abstract

Chromophobe renal cell carcinoma (ChRCC) is the third most common renal cell carcinoma (RCC) subtype, which predominantly occurs in sporadic setting. ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants, classic and eosinophilic. Most ChRCCs carry a favorable clinical outcome. Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features. Along with positive CD117 expression, classic ChRCCs generally express diffuse and uniform CK7, while eosinophilic variant demonstrates more heterogeneous CK7 expression (rare or patchy). Multiple losses of chromosomes 1, 2, 6, 10, 13, 17, and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs, while chromosomal gains are known to be associated with sarcomatoid ChRCCs. TP53 and PTEN are the two most frequently mutated genes in ChRCCs. The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant (of ChRCCs), where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors. Most eosinophilic ChRCCs share expression of the recently described biomarkers, LINC01187 and FOXI1, with classic ChRCCs, however, a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations. Overall, the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct, yet heterogeneous group of renal neoplasms.

Keywords: Chromophobe; Immunohisto-chemistry; Molecular; Next-generation sequencing; Oncocytic tumors; RNA in situ hybridization; Renal cell carcinoma.

Publication types

Review