Histologic Patterns and Germline Genetic Testing Outcomes in Presumed Sporadic Bilateral Renal Masses

Bilateral renal masses (BRMs) are classically linked to inherited familial syndromes, often associated with distinct histologies. Current guidelines recommend genetic counseling for all patients with BRMs; however, the utility of genetic testing in patients with BRMs with apparently sporadic etiology remains unclear. Our objective was to characterize histologic pairings between the index/contralateral renal masses and evaluate the value of genetic testing across histologic subgroups.

We reviewed 527 patients surgically treated for BRMs (2002-2024), and 414 had no evidence of familial etiology. Histologic concordance between the index (first operated) and contralateral renal masses were assessed. Adherence with genetic testing and outcomes were compared across histologic groupings.

Histologic concordance between the index/contralateral masses was observed in most patients: 78% for clear cell, 70% for papillary, and 74% for oncocytic neoplasms. Overall, only 88 patients (21%) were referred for genetic counseling and germline genetic testing was performed in 53 (13%). Pathogenic variants were only observed in 4 patients, including 1 hereditary papillary renal carcinoma, 2 Birt-Hogg-Dubé, and 1 tuberous sclerosis. No pathogenic variants were observed in the bilateral clear cell group.

Among patients with BRMs with apparently sporadic etiology, strong concordance between bilateral histologies was observed. Although guidelines recommend genetic counseling for all patients with BRMs, our findings suggest that testing was underutilized and diagnostic yield was low, particularly for high-risk mutations (eg, von Hippel-Lindau or fumarate hydratase-deficient renal cell carcinoma). These findings suggest that genetic testing for patients with BRMs could be considered selectively, prioritizing patients with extrarenal manifestations, family history, young age, or pathology suspicious for hereditary etiology.