The Gynecologist's Role in the Workup and Management of Patients with Leiomyomas Demonstrating Fumarate Hydratase Deficiency

Abstract

Study Objective Fumarate hydratase (FH) tumor predisposition syndrome or hereditary leiomyomatosis renal cell cancer (HLRCC) is caused by an autosomal-dominant heterozygous mutation in the FH gene. It is characterized by uterine or cutaneous leiomyomas and renal tumors. Timely diagnosis of HLRCC allows for cancer surveillance. Yet, delays in diagnosis are common in patients with isolated uterine findings. Given that leiomyomas are the most common benign tumors in reproductive-aged women, gynecologists are in an opportunistic position to detect HLRCC earlier. In this series, we present three patients with FH-deficient leiomyomas, and review the gynecologist's unique role in screening, workup, and diagnosis of HLRCC. Design Case Series. Setting Academic institution. Patients or Participants Three patients. Interventions Surgery and genetic screening. Measurements and Main Results Case 1 A 33-year-old with heavy menstrual bleeding and an 18cm uterine lesion presents for abdominal myomectomy. Pathological evaluation was suggestive of FH-deficient leiomyoma, which was confirmed by immunohistochemistry (IHC). She was lost to follow up. Case 2 A 32-year-old with pelvic pain, infertility, and a submucosal fibroid presents for robotic myomectomy. Pathology and IHC confirmed a diagnosis of FH-deficient leiomyoma. Genetic testing for FH mutation was negative. Case 3 A 52-year-old with adenomyosis unresponsive to conservative management presents for hysterectomy. Pathological evaluation was suggestive of FH-deficient leiomyoma, however IHC did not support this diagnosis. Genetic testing was negative. Conclusion HLRCC presents with a variation of phenotypes ranging from leiomyomas to metastatic renal cell carcinoma. Our cases underscore the gynecologist's unique role in the diagnosis of HLRCC. The majority of uterine fibroids are not associated with an increased risk malignancy. FH-deficient leiomyomas can occur in both syndromic and sporadic settings. A thorough history can identify patients at risk. Characteristic histopathological features should prompt genetic evaluation. Management requires a multidisciplinary approach and surveillance can be offered to individuals with even a suspected diagnosis in whom an FH mutation has not been identified. Fumarate hydratase (FH) tumor predisposition syndrome or hereditary leiomyomatosis renal cell cancer (HLRCC) is caused by an autosomal-dominant heterozygous mutation in the FH gene. It is characterized by uterine or cutaneous leiomyomas and renal tumors. Timely diagnosis of HLRCC allows for cancer surveillance. Yet, delays in diagnosis are common in patients with isolated uterine findings. Given that leiomyomas are the most common benign tumors in reproductive-aged women, gynecologists are in an opportunistic position to detect HLRCC earlier. In this series, we present three patients with FH-deficient leiomyomas, and review the gynecologist's unique role in screening, workup, and diagnosis of HLRCC. Case Series. Academic institution. Three patients. Surgery and genetic screening. Case 1 A 33-year-old with heavy menstrual bleeding and an 18cm uterine lesion presents for abdominal myomectomy. Pathological evaluation was suggestive of FH-deficient leiomyoma, which was confirmed by immunohistochemistry (IHC). She was lost to follow up. Case 2 A 32-year-old with pelvic pain, infertility, and a submucosal fibroid presents for robotic myomectomy. Pathology and IHC confirmed a diagnosis of FH-deficient leiomyoma. Genetic testing for FH mutation was negative. Case 3 A 52-year-old with adenomyosis unresponsive to conservative management presents for hysterectomy. Pathological evaluation was suggestive of FH-deficient leiomyoma, however IHC did not support this diagnosis. Genetic testing was negative. HLRCC presents with a variation of phenotypes ranging from leiomyomas to metastatic renal cell carcinoma. Our cases underscore the gynecologist's unique role in the diagnosis of HLRCC. The majority of uterine fibroids are not associated with an increased risk malignancy. FH-deficient leiomyomas can occur in both syndromic and sporadic settings. A thorough history can identify patients at risk. Characteristic histopathological features should prompt genetic evaluation. Management requires a multidisciplinary approach and surveillance can be offered to individuals with even a suspected diagnosis in whom an FH mutation has not been identified.