An atypical case of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)-associated renal cell carcinoma identified by next-generation sequencing

摘要

Germline mutations in the fumarate hydratase ( FH ) gene classically lead to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) syndrome. Patients with HLRCC typically exhibit multiple cutaneous and uterine leiomyomas at a young age. They also display a 20–30% lifetime risk for renal carcinomas, which commonly present before 40years of age, have a distinct papillary morphology, and an aggressive phenotype. However, the clinical presentation of HLRCC and the morphology of HLRCC-associated renal cell carcinomas (RCCs) can be variable and thereby evade diagnosis. Here, we present two cases of HLRCC-associated RCC to emphasize this point. The first case is typical of HLRCC, involving a 29-year-old man with multiple cutaneous leiomyomas and a renal tumor with characteristic papillary morphology. Next, we describe a 48-year-old man presenting with metastatic cancer of unknown primary origin and no skin findings. Interestingly, next-generation sequencing of his metastatic tumor identified two unique FH mutations. In both cases, FH mutations were confirmed as germline. These cases highlight the variable presentations of HLRCC-associated RCC and underscore the importance of screening tumors of unknown origin for FH mutations using next-generation sequencing.