Leiomyoma with Bizarre Nuclei and Hereditary Leiomyomatosis and Renal Cell Carcinoma

Leiomyoma with bizarre nuclei (LBN) is a leiomyoma variant that can be associated with fumarate hydratase (FH) deficiency. Germline pathogenic variants in the FH gene are linked to hereditary leiomyomatosis and renal cell carcinoma (HLRCC), which presents with cutaneous leiomyomata, aggressive renal cell carcinomas (RCCs), and symptomatic uterine leiomyomas.

A 22-year-old nulligravida female presented with multiple uterine fibroids, heavy menstrual bleeding and pelvic pain, lasting over two years. The patient subsequently underwent laparoscopic myomectomy. Histological analysis of the leiomyomas indicated the presence of bizarre nuclei. Immunohistochemical studies confirmed FH deficiency, characterized by loss of FH expression and overexpression of S-(2-succino)-cysteine (2SC). Genetic testing revealed a likely pathogenic variant (c. 1176_1181delTGCTGT) in the FH gene.

Due to potentially devastating consequence and the occult nature of RCCs, the discovery of LBN should be followed with further investigation for HLRCC.