PMID- 34168281 OWN - NLM STAT- MEDLINE DCOM- 20220318 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 34 IP - 11 DP - 2021 Nov TI - Myxoid pleomorphic liposarcoma-a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma. PG - 2043-2049 LID - 10.1038/s41379-021-00862-2 [doi] AB - 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. CI - (c) 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. FAU - Creytens, David AU - Creytens D AD - Department of Pathology, Ghent University Hospital, Ghent, Belgium. david.creytens@uzgent.be. AD - Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium. david.creytens@uzgent.be. FAU - Folpe, Andrew L AU - Folpe AL AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. FAU - Koelsche, Christian AU - Koelsche C AUID- ORCID: 0000-0001-8763-8864 AD - Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. FAU - Mentzel, Thomas AU - Mentzel T AD - Dermatopathology Bodensee, Friedrichshafen, Germany. FAU - Ferdinande, Liesbeth AU - Ferdinande L AD - Department of Pathology, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium. FAU - van Gorp, Joost M AU - van Gorp JM AD - Department of Pathology, St Antonius Hospital, Nieuwegein, The Netherlands. FAU - Van der Linden, Malaika AU - Van der Linden M AD - Department of Pathology, Ghent University Hospital, Ghent, Belgium. AD - Center for Medical Genetics, Ghent University, Ghent, Belgium. FAU - Raman, Lennart AU - Raman L AUID- ORCID: 0000-0002-3840-5930 AD - Department of Pathology, Ghent University Hospital, Ghent, Belgium. AD - Center for Medical Genetics, Ghent University, Ghent, Belgium. FAU - Menten, Bjorn AU - Menten B AD - Center for Medical Genetics, Ghent University, Ghent, Belgium. FAU - Fritchie, Karen AU - Fritchie K AUID- ORCID: 0000-0003-2336-3691 AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. FAU - von Deimling, Andreas AU - von Deimling A AUID- ORCID: 0000-0002-5863-540X AD - Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. FAU - Van Dorpe, Jo AU - Van Dorpe J AUID- ORCID: 0000-0001-8175-2930 AD - Department of Pathology, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium. FAU - Flucke, Uta AU - Flucke U AD - Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210624 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (DNA, Neoplasm) RN - 0 (Neoplasm Proteins) SB - IM MH - Adolescent MH - Adult MH - DNA Methylation MH - DNA, Neoplasm/*genetics MH - Epigenomics MH - Female MH - Head and Neck Neoplasms/*classification/genetics/metabolism/pathology MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Liposarcoma/*classification/genetics/metabolism/pathology MH - Liposarcoma, Myxoid/*classification/genetics/metabolism/pathology MH - Male MH - Mediastinal Neoplasms/*classification/genetics/metabolism/pathology MH - Middle Aged MH - Molecular Biology MH - Neoplasm Proteins/*genetics/metabolism MH - Soft Tissue Neoplasms/*classification/genetics/metabolism/pathology MH - Whole Genome Sequencing MH - Young Adult EDAT- 2021/06/26 06:00 MHDA- 2022/03/19 06:00 CRDT- 2021/06/25 06:42 PHST- 2021/02/15 00:00 [received] PHST- 2021/06/16 00:00 [accepted] PHST- 2021/06/15 00:00 [revised] PHST- 2021/06/26 06:00 [pubmed] PHST- 2022/03/19 06:00 [medline] PHST- 2021/06/25 06:42 [entrez] AID - S0893-3952(22)00512-9 [pii] AID - 10.1038/s41379-021-00862-2 [doi] PST - ppublish SO - Mod Pathol. 2021 Nov;34(11):2043-2049. doi: 10.1038/s41379-021-00862-2. Epub 2021 Jun 24.