Timely recognition of a probably life-threatening genodermatosis: familial case report of hereditary leiomyomatosis and renal cell cancer.

Background: Autosomal dominant genodermatoses with a predisposition for cancer make up a well-described disease group with unique cutaneous alterations in each. This should urge dermatologists to think of other consequences beyond the skin. Histological examination serves as the gold standard, and it is an effective tool for the first investigation, even nowadays in the "next-generation genetic" era. Multiple appearances of benign tumours histologically proved to be cutaneous leiomyomatosis suggest a rare disorder with germline heterozygous pathogen variant in the FH gene. The encoded fumarate hydratase is a Krebs cycle enzyme, and has a role in catalysing the transition from fumarate to malate.

Case presentation: Years before the easy accessibility of the complete genetic workup in Hungary, a yearly abdominal MRI check-up was suggested preventively for a middle-aged man with multiplex cutaneous leiomyomata. During the follow-up period papillary type 2 renal cell carcinoma was diagnosed in the left kidney at an early stage, and a successful operation saved his life without the need for aggressive chemotherapy or immunotherapy. Immunohistochemistry of tumour tissue proved FH-deficient renal cell cancer. We discuss in short the current knowledge of pathophysiology and accessible therapies regarding this aggressive malignant tumour type in the kidney, which is usually detected in the advanced stage with early metastasis. We also highlight an early sign, i.e., solitary cystic alteration in the kidney, which can be preliminarily observed before malignant transformation, which was also described in mouse models. Sanger sequencing and Multiplex-Ligation-Dependent Probe Amplification (MLPA) analysis of the FH gene was completed in the affected son of the original proband, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) was confirmed by demonstrating a large germline deletion in this family after years of observation.

Conclusion: Regular observation of individuals with hereditary leiomyomatosis may prevent a serious sequelae of untreatable renal malignancy.