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 with other sarcomas, particularly other liposarcomas. Available slides/blocks for cases coded as "MPLPS" were retrieved (2008-2026). We also searched our single-nucleotide polymorphism assay records for tumors demonstrating (1) high cnLOH frequency (>30%) and (2) "liposarcoma" or "pleomorphic sarcoma" diagnosis. Nonmesenchymal tumors were excluded. Twenty-four MPLPS cases were identified, occurring in 10 women (42%) and 14 men (58%), ranging from 5 to 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. Single-nucleotide polymorphism testing (n = 22) demonstrated cnLOH of >50% in 19 cases (86%), often with pseudohyperdiploidy. One tumor showed cnLOH of 38%; 2 otherwise-typical tumors did not have widespread cnLOH. Other recurrent alterations included gains of chromosomes 1/1q, 6 to 8, and 18 to 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 nonmediastinal locations. Although most MPLPS harbor widespread cnLOH, rare otherwise-typical tumors do not. MPLPS are aggressive sarcomas with poor prognosis.