Myxoid Pleomorphic Liposarcoma: A Clinicopathological and Cytogenomic Study of 24 Cases

Myxoid pleomorphic liposarcoma (MPLPS), a rare, aggressive liposarcoma subtype, is thought to occur chiefly in adolescents with a mediastinal predilection. MPLPS lack DDIT3 rearrangements or MDM2 amplification; a small number have recently been shown to harbor widespread copy-neutral loss of heterozygosity (cnLOH). We studied a large series of MPLPS and compared them to other sarcomas, particularly other LPS. Available slides/blocks for cases coded as "MPLPS" were retrieved (2008-2026). We also searched our single nucleotide polymorphism (SNP) assay records for tumors demonstrating 1) high cnLOH frequency (>30%), and 2) "liposarcoma" or "pleomorphic sarcoma" diagnosis. Non-mesenchymal tumors were excluded. Twenty-four MPLPS cases were identified, occurring in 10 females (42%) and 14 males (58%), ranging from 5-85 years of age (median 46 years). Involved anatomical locations included the mediastinum/thorax (n=12), trunk (n=3), head and neck (n=3), various intra-abdominal sites (n=3), retroperitoneum/pelvis (n=2) and extremities (n=1). Two patients had clinical features of Li-Fraumeni syndrome or a germline TP53 mutation. All tumors displayed characteristic features of MPLPS, including areas resembling conventional myxoid liposarcoma and hypercellular, pleomorphic liposarcoma-like foci. SNP testing (n=22) demonstrated cnLOH of >50% in 19 cases (86%), often with pseudohyperdiploidy. One tumor showed cnLOH of 38%; two otherwise typical tumors did not have widespread cnLOH. Other recurrent alterations included gains of chromosomes 1/1q, 6- 8, and 18-21 and loss of chromosome 14. Specific losses/gains involving the RB1 and TP53 loci were seen in 12 and 2 cases, respectively. Clinical follow-up (n=22; median 16 months; range 1-75 months) showed 9 patients dead of disease (median survival 12 months), 6 patients alive with disease, and 6 patients alive without disease. Local recurrences and distant metastases were seen in 6 and 8 patients, respectively. We conclude that the age range and anatomical distribution of MPLPS are considerably wider than has been previously appreciated, including tumors arising in the elderly and various non-mediastinal locations. Although most MPLPS harbor widespread cnLOH, rare otherwise-typical tumors do not. MPLPS are aggressive sarcomas with poor prognosis.