FH-deficient uterine leiomyoma in young women requires IHC screening and lifelong renal surveillanceRare Genetic Marker Linked to Multiple Uterine Fibroids

BackgroundUterine leiomyoma is the most common benign tumor in the female reproductive system. Fumarate hydratase (FH)-deficient leiomyoma is a rare subtype characterized by distinctive histopathological and immunophenotypic features and may be associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.Case descriptionA 35-year-old Han Chinese woman, gravida 1 para 1, was admitted in 2021 because of multiple uterine leiomyomas. Pelvic ultrasound demonstrated an enlarged uterus with multiple intramural masses, including a cervical lesion measuring 12.8×10.8×10.3 cm. The patient underwent open abdominal myomectomy. Histopathology showed multiple leiomyomas with focally increased cellularity and occasional mitotic activity. Immunohistochemistry demonstrated CD10 negativity and positivity for SMA, desmin, h-caldesmon, and ER, whereas FH and 2SC staining were not performed at that time. Five months after surgery, multiple intramural masses were detected on ultrasound, but the patient was lost to follow-up for approximately 4 years. In 2025, she presented with irregular vaginal bleeding. Imaging revealed multiple large hypervascular uterine masses with ill-defined margins, heterogeneous echogenicity, and degenerative changes on MRI. The patient reported that both her mother and sister had undergone hysterectomy for uterine fibroids. She subsequently underwent total hysterectomy with bilateral salpingo-oophorectomy. Pathological examination demonstrated multiple intramural leiomyomas with degeneration and focal infarction. Immunohistochemistry revealed loss of FH expression and diffuse strong 2SC positivity,confirming FH-deficient uterine leiomyoma. Abdominal CT showed no renal abnormality. FH genetic testing, genetic counseling, and lifelong renal and dermatologic surveillance were recommended, but the patient declined genetic testing. At 6-month follow-up, she remained asymptomatic without imaging evidence of recurrence.ConclusionFH-deficient uterine leiomyoma should be suspected in young women presenting with large, multiple, recurrent, hypervascular leiomyomas and familial clustering of uterine fibroids. Early FH/2SC immunohistochemical screening, genetic counseling, and long-term renal surveillance are important for identifying suspected HLRCC risk and guiding individualized management. Even when germline FH testing is declined, patients with FH-deficient uterine leiomyoma should not be managed as routine leiomyoma cases, but should receive counseling regarding suspected HLRCC risk, dermatologic assessment, and lifelong renal surveillance.