Case Report: A rare case of fumarate hydratase (FH)-deficient uterine leiomyoma in a 39-year-old woman: a sentinel finding prompting hereditary cancer syndrome evaluation.

BACKGROUND: Fumarate hydratase (FH)-deficient uterine leiomyoma is a rare pathologic marker for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Its recognition is crucial for initiating life-saving surveillance.

CASE PRESENTATION: We report the case of a 39-year-old woman from a minority ethnic background presenting with a pelvic mass and progressive heavy menstrual bleeding culminating in severe anemia (hemoglobin 5.8 g/dL). Imaging revealed numerous uterine leiomyomas. She underwent an open myomectomy. Histopathological examination confirmed the diagnosis of FH-deficient leiomyoma, supported by immunohistochemistry showing complete loss of FH expression and strong positivity for 2-succinocysteine (2SC). This pathological finding served as a sentinel event, prompting clinical evaluation for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, regardless of germline status.

CONCLUSION: This case highlights that the presentation of multiple leiomyomas with rapid symptom progression in a young woman should raise clinical suspicion for an underlying syndromic association. Pathologic confirmation via FH/2SC immunohistochemistry is pivotal and alone warrants initiation of renal surveillance, as recommended by current guidelines. The diagnosis mandates a multidisciplinary strategy involving genetic counseling, offering germline FH mutation testing, and proactive renal surveillance, thereby shifting management from a surgical problem to comprehensive cancer prevention.