A rare variant of RCC with clear-cell cytology and fibromyomatous stroma, but without 3p loss or alterations affecting VHL, PBRM1, SETD2 or BAP1. ¹ Biallelic inactivation of elongin C, ELOC, formally ELOC at 8q21, according to a combination of somatic mutation and -8/8q deletion, in  classical tumor suppressor behavior. ²

Rare tumors with a median age of 60 years.

Well-circumscribed, typically with a thick fibrous capsule

Tumors composed of cells with abundant clear cytoplasm showing varied architectural patterns (predominatly tubular or tubulopapillary growth) with thick fibromuscular bands transecting the tumor.  The morphology of these tumors are non-specific and overlap with other subtypes of renal neoplasia.

CK7 (patchy to moderate) and CA-IX (diffuse, complete membranous staining), variable AMACR and CD10 expression, and are negative for high–molecular-weight cytokeratin expression. ³

Variable clinical course; its behavior can range from very indolent to rare cases of metastatic and aggressive behavior. ² Genetic testing for ELOC variants should be performed in individuals with suspected VHL disease with no detectable VHL variant. ⁴

Monosomy 8, mainly as the sole chromosome aberration, which can be detected by conventional karyotype (Fig.1A) FISH analysis (Fig.1B) and copy number variation (SNP microarray or NGS) (Fig.1C).  Gains of chromosome 7, but no other recurrent events were noted. ³

Fig.1: Monosomy 8 can be detected by conventional karyotype (A), FISH analysis (B) or copy number variation (SNP microarray or NGS) (C) and example of ELOC mutation affected Y79 residue (D)

ELOC mutations  (Fig. 1D) ⁵ mainly affected Y79 residue; all  mutated aminoacids  are involved in hydrophobic interactions with VHL.  High-grade/stage cases contained other potential oncogenic drivers as TERT promotor hot spot and other genes commonly affected in CCRCC as SETD2,PIK3CA, and TP53. ² They lack secondary alterations in tumors suppressors such as PBRM1, and mutations in genes such as SETD2, KDM5C and BAP1. ^3,6

ELOC-mutated tumors showed mRNA downregulation of multiple components involved in RNA Pol II elongation such as ELOC, ELOB, POLR2C, POLR2E, and CDK7. ³

Specific molecular events leading to high genomic instability as additional oncogenic mutations and whole-genome doubling events seem to be associated with aggressiveness. ²