Comprehensive Analysis of 15 Cases of ELOC-RCC and Identification of Novel Mutation Site.

Abstract

ELOC-mutated renal cell carcinoma (ELOC-RCC), a newly recognized tumor entity in the fifth edition of the WHO Classification of Tumors of Urinary and Male Genital Organ Tumors (5th WHO Classification), presents morphologic and immunohistochemical (IHC) features overlapping those of clear cell RCC (ccRCC), RCC with fibromyomatous stroma (RCC-FMS), and clear cell papillary renal cell tumor (ccPRCT). Confirmation of an ELOC mutation is required for a definitive diagnosis. This study aims to enhance the understanding of ELOC-RCC's morphologic and molecular characteristics and to develop an affordable and practical panel for its preliminary differentiation based on morphologic and IHC features. Representing one of the largest cohorts of ELOC-RCC, this research involved a retrospective analysis of 56 suspected cases at Shanghai Ruijin Hospital from January 2022 to March 2024, identifying 15 cases through next-generation sequencing (NGS). We report an ELOC mutation site (c.274G>A, p.Glu92Lys), which has not been previously reported in the literature. NGS analysis also showed recurrent mutations in MAP2K4 and HRAS in ELOC-RCC, though their implications are not yet clear. In addition, we describe a case of ELOC-RCC with a PARP4 mutation. Our findings indicate that the "basally polarized" nuclear arrangement and the "apical/apicolateral polarized" staining patterns of CD10 and EMA offer valuable diagnostic clues for differentiating ELOC-RCC from low-grade ccRCC. Furthermore, the immunophenotypic profile of CD10+/AMACR+/GPNMB- appears helpful for differentiating ELOC-RCC from both ccPRCT and mTOR pathway-mutated RCC-FMS (mTOR-RCC-FMS). However, genetic testing remains indispensable, as evidenced by one CK7-negative ELOC-RCC case.