L1CAM expression in eosinophilic solid and cystic renal cell carcinoma: clinicopathologic and immunophenotypic insights from a multicenter cohort.

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a recently recognized eosinophilic renal neoplasm characterized by distinctive morphologic, immunophenotypic, and molecular features, including frequent TSC/mTOR pathway alterations. Recently, L1 cell adhesion molecule (L1CAM) has gained increasing recognition as a diagnostically and biologically relevant marker in selected eosinophilic renal neoplasms; however, its expression profile in ESC-RCC has not been systematically investigated. We aimed to evaluate L1CAM expression in a multicenter cohort of ESC-RCCs and correlate the findings with clinicopathologic and immunophenotypic features. A retrospective multicenter cohort of 11 ESC-RCCs was collected. Clinicopathologic and immunophenotypic findings were recorded. Immunohistochemistry for L1CAM was performed on representative whole tissue sections and semi-quantitatively scored based on the percentage of positive tumor cells. The cohort included 9 female and 2 male patients with a median age of 50 years (range, 39-79). L1CAM expression was identified in 7 of 11 tumors (63.6%), including 5 cases with diffuse membranous (3+) staining and 2 cases with intermediate (2+) staining; no tumor showed only focal (1+) expression. All tumors showed the characteristic morphology of ESC-RCC and expressed KRT20, irrespective of L1CAM status. Among tumors evaluated with additional markers, SDHB expression was retained in all 6 tested tumors and GATA3 was negative in all 5 tested tumors. Molecular testing was not performed in this cohort. Follow-up was available for all 11 patients (median, 10 months), with all patients alive without disease at last follow-up. Our findings expand the known immunophenotypic spectrum of ESC-RCC by demonstrating L1CAM expression in a substantial subset of tumors. However, because L1CAM expression is neither sensitive nor specific for ESC-RCC, positive or negative staining does not support or exclude the diagnosis and does not currently justify routine use of L1CAM in the diagnostic evaluation of morphologically suspected ESC-RCC.