ELOC-mutant renal cell carcinoma: practical diagnostic features and differential considerations

ELOC (TCEB1)-mutant renal cell carcinoma (RCC) is a recently recognised entity in the 2022 WHO classification. Due to overlapping features, it is frequently misdiagnosed as clear cell RCC (CCRCC). This study characterises the clinicopathological, immunohistochemical and molecular features of six ELOC-mutant RCCs to aid in their diagnostic distinction.

Twenty-eight RCCs initially diagnosed as CCRCC with cytokeratin 7 (CK7) positivity and/or fibromuscular stroma were re-evaluated. Sanger sequencing was performed to detect ELOC mutations. The histopathological and immunophenotypic features of the six mutation-positive tumours were compared with those of the remaining 22 cases.

The six ELOC-mutant tumours occurred in five men and one woman. All specimens showed a multinodular architecture, separated by a thick fibromuscular stroma. Tumour cells exhibited tubular, papillary, nested and tubulocystic patterns, with small branching papillae often present within cysts. The cytoplasm was predominantly clear, and nuclei were low-grade and basally oriented. CK7 expression was moderate to strong, with diffuse membranous staining in papillary areas. Sanger sequencing confirmed ELOC point mutations in all cases. In contrast, CCRCCs with fibromuscular stroma were rare, more often exhibited eosinophilic cytoplasm, lacked papillary structures and showed negative or only focal expression of CK7. Sanger sequencing showed the wild-type ELOC genotype.

ELOC-mutant RCC exhibits distinctive morphologic and immunohistochemical features; however, a definitive diagnosis requires molecular confirmation. Recognition of its characteristic features, including clustered branching papillae, CK7 positivity in papillary regions and the lack of correlation between cytoplasmic and nuclear grade, can guide appropriate ancillary testing and improve diagnostic accuracy.