[Hereditary leiomyomatosis and renal cell carcinoma syndrome : Pathological features, diagnostics, and clinical...

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a rare, autosomal dominant tumor predisposition syndrome. It is characterized by the early onset of cutaneous and uterine leiomyomas as well as aggressive renal cell carcinomas (RCC).

This review focuses on the characterization of HLRCC syndrome, its clinical manifestations, and histopathological and molecular diagnostics to optimize the identification of affected patients and families.

The review was conducted based on the current WHO classifications of female genital tumours, urinary and male genital tumours, and genetic tumor syndromes, as well as the current German S3 guideline for renal cell carcinoma, supplemented by a selective literature review focusing on the key clinical and morphological features.

The syndrome is caused by germline mutations in the fumarate hydratase (FH) gene. FH-deficient tumours are highly characteristic but not entirely specific for HLRCC. While uterine leiomyomas occur in up to 80% of affected women and often require early surgical treatment, at least 15% of patients develop aggressive renal cell carcinoma. The diagnosis is based on characteristic morphology, immunohistochemistry (including FH deficiency), and detection of the germline mutation.

Given the potentially aggressive renal manifestation, early pathological identification of FH-deficient tumours plays a central role, as it enables the initiation of genetic testing and structured screening for affected patients and families.