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.