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

Chromophobe renal cell carcinoma: Novel molecular insights and clinicopathologic updates

Reza Alaghehbandan  1 , Christopher G Przybycin  2 , Virginie Verkarre  3 , Rohit Mehra  4   5   6
Affiliations
Review

Chromophobe renal cell carcinoma: Novel molecular insights and clinicopathologic updates

Reza Alaghehbandan et al. Asian J Urol. 2022 Jan.

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.

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Figures

Figure 1
Figure 1
Classic and sarcomatoid ChRCCs. (A) Classic ChRCC H & E stain; (B) Sarcomatoid ChRCC H & E stain; (C) Membranous staining for CD117; (D) High-level nuclear LINC01187 expression. All images are at 200×. ChRCC, chromophobe renal cell carcinoma; H & E, hematoxylin and eosin.
Figure 2
Figure 2
Eosinophilic variant of ChRCC. (A) Eosinophilic variant of ChRCC H&E stain; (B) Predominantly membranous staining for CD117; (C) The nuclear staining for FOXI1 in eosinophilic variant of ChRCC; (D) High-level nuclear LINC01187 expression; (E) Another example of eosinophilic variant of ChRCC H & E stain; (F) With negative CD117 expression and MTOR gene mutation (data not shown). All images are at 200×. ChRCC, chromophobe renal cell carcinoma; H & E, hematoxylin and eosin.
Figure 3
Figure 3
Distribution of chromosomal losses and gains in classic, eosinophilic and sarcomatoid ChRCC. ChRCC, chromophobe renal cell carcinoma.
See this image and copyright information in PMC

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