A clinicopathological and molecular analysis in uterine leiomyomas and concurrent/metachronous peritoneal nodules: New insights into disseminated peritoneal leiomyomatosis

Abstract

Disseminated peritoneal leiomyomatosis (DPL) is a rare, benign entity, but DPL following morcellation has become a major concern recently. This study aimed to investigate the molecular relationship between uterine leiomyoma and DPL. We analyzed the clinicopathological and molecular features of 8 DPL patients including 6 (#3–8) with and 2 (#1 and 2) without antecedent morcellation. Patients 1 and 2 were characterized by numerous, small peritoneal nodules whereas patients 4–8 harbored less but larger peritoneal nodules. Patient 3 had a peritoneal carcinomatosis-like dissemination, but she has been alive with disease for 68 months. Histological examination confirmed the diagnosis of leiomyomas in the uterus and extra-uterine sites. Immunohistochemistry demonstrated that both uterine and extra-uterine tumors were invariably positive for HMGA2 and MED12. MED12 mutation (c.130 G > A, p.G44S) was found in original uterine (n = 3) and peritoneal (n = 11) tumors from patients 3, 6, 7 and 8. Microsatellite instability at TPOX and D19S433 was observed in the uterine leiomyoma (patient 2) whereas LOH at CSF1PO was found in the peritoneal tumors (patient 1). D13S317 LOH was present in both uterine and peritoneal tumors detected (patient 8). However, D3S1358 LOH and D19S433 LOH was only found in the peritoneal tumors (patient 8) and recurrent tumors (patient 3), respectively. We suggested that DPLs following morcellation might be closely associated with original uterine leiomyomas. DPLs with and without prior morcellation may harbor different pathogenetic pathways. These findings are critical for the clinical intervention and prevention of DPL patients.