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

Carsten Holzmann,Dirk Koczan,Jörn Bullerdiek,Burkhard M Helmke,Gunhild Mechtersheimer,Christian Saager

doi:10.18632/oncotarget.25137

Carsten Holzmann, Dirk Koczan + Show 4 more

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https://doi.org/10.18632/oncotarget.25137

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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.

Highlights

Being part of minimal-invasive removal of uterine leiomyomas or hysterectomy, power morcellation of tissue specimens carries the risk of unexpected spreading of cancerous tissue, e.g. derived from leiomyosarcomas, within the abdomen and pelvis
After laparoscopic supracervical hysterectomy (LASH), five tumor samples were paraffin-embedded for histologic examination which in all samples confirmed the presence of leiomyomas (Figure 1A)
Because of a possible origin of the leiomyomsarcoma from a morcellated tumor, genomic profiles from four samples obtained from initial surgery as well as from the tumor that was detected 28 month later were investigated by copy number/SNP-array hybridization using the molecular inversion probe (MIP)

Summary

Introduction

Being part of minimal-invasive removal of uterine leiomyomas or hysterectomy, power morcellation of tissue specimens carries the risk of unexpected spreading of cancerous tissue, e.g. derived from leiomyosarcomas, within the abdomen and pelvis. Risk figures are mostly based on retrospective analyses of the tissue removed and vary over a broad range [3] On the other hand, follow-up of those tumors classified as benign is usually lacking [4,5,6] though the results of thorough histologic examinations as well as of recent genetic analyses suggest that, albeit rarely, leiomyomas can undergo malignant transformation and that a considerable percentage of leiomyosarcomas still contain areas displaying “benign” histology [7]. It seems tempting to assume that data obtained after tumor morcellation [8,9,10,11] are not suited to correctly assess the risk to benefit ratio of morcellation merely resulting from statistical problems [12]: A large percentage of patients have more than one tumor but once the specimen has been morcellated it is, as a rule, no longer possible to allocate the sample to an individual tumor despite some sampling recommendations [13]

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