Myxoid pleomorphic liposarcoma is a recently defined subtype of liposarcoma, which preferentially involves the mediastinum of young patients and shows mixed histological features of conventional myxoid liposarcoma and pleomorphic liposarcoma. While myxoid pleomorphic liposarcoma is known to lack the EWSR1/FUS-DDIT3 fusions characteristic of the former, additional genetic data are limited. To further understand this tumor type, we extensively examined a series of myxoid pleomorphic liposarcomas by fluorescence in situ hybridization (FISH), shallow whole genome sequencing (sWGS) and genome-wide DNA methylation profiling. The 12 tumors occurred in 6 females and 6 males, ranging from 17 to 58 years of age (mean 33 years, median 35 years), and were located in the mediastinum (n = 5), back, neck, cheek and leg, including thigh. Histologically, all cases consisted of relatively, bland, abundantly myxoid areas with a prominent capillary vasculature, admixed with much more cellular and less myxoid foci containing markedly pleomorphic spindled cells, numerous pleomorphic lipoblasts and elevated mitotic activity. Using sWGS, myxoid pleomorphic liposarcomas were found to have complex chromosomal alterations, including recurrent large chromosomal gains involving chromosomes 1, 6–8, 18–21 and losses involving chromosomes 13, 16 and 17. Losses in chromosome 13, in particular loss in 13q14 (including RB1, RCTB2, DLEU1, and ITM2B genes), were observed in 4 out of 8 cases analyzed. Additional FISH analyses confirmed the presence of a monoallelic RB1 deletion in 8/12 cases. Moreover, nuclear Rb expression was deficient in all studied cases. None showed DDIT3 gene rearrangement or MDM2 gene amplification. Using genome-wide DNA methylation profiling, myxoid pleomorphic liposarcomas and conventional pleomorphic liposarcomas formed a common methylation cluster, which segregated from conventional myxoid liposarcomas. While the morphologic, genetic and epigenetic characteristics of myxoid pleomorphic liposarcoma suggest a link with conventional pleomorphic liposarcoma, its distinctive clinical features support continued separate classification for the time being.
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We are very grateful for technical assistance to Isabelle Rottiers and Lynn Supply (Department of Pathology, University Hospital Ghent, Belgium) and Tamara De Clercq (Center for Medical Genetics, Ghent University, Ghent, Belgium). We thank the Microarray unit of the Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ) for providing excellent DNA methylation services. This work was supported by the German Cancer Aid (Grant no. 70112499).
The DNA methylation profiling part in this study was supported by the German Cancer Aid (Grant no. 70112499). Other authors received no specific funding for this work.
Ethics approval and consent to participate
This study was approved by the Institutional Review Board of the Ghent University Hospital/Ghent University (approval number/ID B670201938578). This study was performed in accordance with the Declaration of Helsinki and with the Code of Conduct of the Federation of Medical Scientific Societies in the United States of America, Belgium, the Netherlands, and Germany.
The authors declare no competing interests.
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Creytens, D., Folpe, A.L., Koelsche, C. et al. Myxoid pleomorphic liposarcoma—a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma. Mod Pathol (2021). https://doi.org/10.1038/s41379-021-00862-2