Fumarate hydratase (FH)-deficient uterine leiomyoma mimicking malignancy: A diagnostic challenge

Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They have some unique histological characteristics and can be linked to renal cell carcinoma (HLRCC) syndrome and hereditary leiomyomatosis. Only pathologic investigation can identify the uncommon subtype of uterine fibroids known as fumarate hydratase-deficient (FH-d) fibroids. The earliest sign of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome could be FH-d uterine fibroids. A young female in her 30s presented to the endocrinology clinic at a tertiary care hospital for a subfertility consultation. She had a history of poorly controlled hypertension. She reported having regular menstrual cycles lasting 28 days, with no complaints of menstrual irregularity or weight loss. Additionally, she had no prior pregnancy or history of spontaneous abortions. Imaging demonstrated a large subserosal fibroid with normal ovaries. After a loss of follow-up for approximately 2 years, the patient presented to the emergency department with a complaint of non-radiating epigastric pain for 1.5 months which was aggravating with time and became the cause of her acute presentation. Additionally, she also complained of interval development of a cutaneous nodule in the right inguinal region and a soft bulge around the umbilicus. This time imaging redemonstrated subserosal fibroid but with atypical features. The lesion showed ill-defined margins and heterogenous enhancement. Associated mild ascites which seems to be increased in magnitude from prior examination, mild omental stranding, and right-sided pleural effusion. Based on these findings, the possibility of malignant transformation was raised. Patient after a multidisciplinary consensus was scheduled for surgical resection. Post-surgical biopsy revealed a FH-deficient leiomyoma with no evidence of necrosis. The excised skin lesion showed features of fibroepithelial growth. Due to the lack of specific radiographic features, a FH enzyme-deficient fibroid, also known as an FH-deficient uterine leiomyoma, usually appears as a normal-looking uterine fibroid on imaging. However, clinical presentations such as early onset, multiple large fibroids, skin lesions, or a family history of renal cell carcinoma may raise suspicion for additional investigation and genetic testing to confirm FH deficiency.