A Case Series of Hereditary Leiomyomatosis and Renal Cell Carcinoma - Treatment Related Toxicity and Unusual Presentations

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition caused by germline mutations in the fumarate hydratase (FH) gene, which encodes the enzyme that converts fumarate to malate in the Krebs cycle. Inactivation of the FH gene predisposes patients to a triad of cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cell carcinoma termed FH deficient/hereditary leiomyomatosis and associated renal cell carcinoma (FH deficient/HLRCC associated RCC). HLRCC associated RCC has been reported to occur in 10-20% of patients with a HLRCC germline mutation. We are reporting a case series of three patients with HLRCC who developed early, aggressive renal carcinoma with metastasis, unusual presentations or unexpected treatment toxicity. We envisage that this will highlight the complexity of presentations of this rare syndrome, importance of early recognition and diagnosis and demonstrate considerations that need to be accounted for during management.