Malignant transformation of uterine leiomyoma to myxoid leiomyosarcoma after morcellation associated with ALK rearrangement and loss of 14q

Abstract

A 50 year old woman underwent laparoscopic supracervical hysterectomy because of symptomatic fibroids. Histologic examination of samples obtained after morcellation revealed typical uterine leiomyomas in all samples investigated. 28 and 47 months later, respectively, the patient presented with peritoneal spreading of nodules that were surgically removed and histologically classified as leiomyosarcoma. In 3/4 of samples obtained after morcellation copy number/SNP-array hybridization showed complex genomic alterations widely identical to the pattern characterizing the sarcoma. Therefore, we conclude that the leiomyosarcoma had unambiguously developed from one of the leiomyomas as a result of secondary genetic alterations i.e. a rearrangement of ALK and a del(14q). The case is challenging the current risk estimates for spreading of unexpected malignant uterine tumors due to power morcellation and highlights the relevance of certain genetic alterations for rare malignant transformation of uterine benign smooth muscle tumors.

Reasons to Reconsider Risk Associated With Power Morcellation of Uterine Fibroids

“…This is in accordance with previous studies demonstrating the presence of morphologically benign tumoral areas in a considerably high percentage of leiomyosarcomas (42,43), as well as common genetic alterations as outlined above and summarized by Mittal et al (42). In addition, patients apparently experiencing malignant transformation of leiomyomas, atypical leiomyomas, benign metastasizing leiomyomas or STUMP to leiomyosarcomas (33,(44)(45)(46)(47) have been described repeatedly. In contrast, evidence for the existence of a considerable percentage of STUMP or leiomyosarcomas with HMGA2 rearrangement is lacking.…”

“…While in none of the samples examined was histopathological evidence for malignancy noted, she presented again more than 2 years later with peritoneal nodules of a leiomyosarcoma. Akin to a fingerprint, these lesions revealed identical characteristic patterns of healed chromothripsis when compared with one of the initial tumors by genomic comparative hybridization (33). This case would have had escaped attention in any of the studies dealing only with the prevalence of primary LMS detected at the time of initial surgery.…”

“…Some of these latter genetic alterations, e.g. full or partial monosomy of chromosome 22, may endow tumors with a higher risk of malignant transformation (32,33).…”

Magnetic resonance imaging findings of a myxoid leiomyosarcoma of the uterus: A case report and literature review

“…Delayed and prolonged enhancement can be observed because of the presence of a myxoid stroma [ 3 ]. In the literature, to the best of our knowledge, reported MRI features of uterine MLMS have been limited to two cases with T2WIs and contrast-enhanced T1-weighted images (T1WIs) [ 4 , 5 ]. Therefore, MRI features of uterine MLMS have not been completely investigated; in particular, features on diffusion-weighted images (DWIs) and dynamic contrast-enhanced (DCE) MRI scans have not been reported in patients with uterine MLMS.…”

Liquid Biopsy as a Tool for Differentiation of Leiomyomas and Sarcomas of Corpus Uteri

“…In addition, inflammatory myofibroblastic tumors are quite rare in the uterus, but can closely mimic both benign and malignant variants of UMT [13]. Debate also continues concerning whether uterine leiomyosarcomas (LMS) arise from malignant transformation of ULM [14,15,16], but, herein, we consider ULM and LMS two separate entities, as generally assumed [5].…”