Pathology-Driven Diagnosis of Hereditary Leiomyomatosis and Renal Cell Carcinoma: A Clinicopathological and Genetic Analysis of Three Cases.

Abstract

INTRODUCTION: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant disorder characterized by three principal clinical features: cutaneous leiomyomas (cLMs), uterine leiomyomas, and fumarate hydratase (FH)-deficient renal cell carcinoma (RCC). Although 200-300 families have been identified worldwide, its true prevalence remains unknown. CASE PRESENTATIONS: We present three HLRCC cases in which detailed pathological examination raised initial clinical suspicion. Cases 1 and 2 presented with advanced RCC exhibiting diverse morphologies. Case 3 presented with multiple painful cLMs and no renal tumors. All three cases were confirmed via germline genetic testing, which revealed distinct FH mutations. CONCLUSIONS: These cases underscore the importance of careful histopathological and immunohistochemical evaluation for the diagnosis of HLRCC. Multidisciplinary discussion integrating clinical, radiological, pathological, and genetic findings is essential for identifying affected families and initiating timely surveillance.