Genomic alterations

Atypical lipomatous tumor. This entity is characterized by supernumerary ring and giant marker chromosomes that contain chromosomal region 12q14-q15, which includes MDM2. MDM2 amplification can be detected in virtually all cases of atypical lipomatous tumor/well-differentiated liposarcoma, with nearby genes such as CDK4 and FRS2 commonly being coamplified with MDM2.[13]

Dedifferentiated liposarcoma. This entity, like atypical lipomatous tumor, is characterized by MDM2 amplification and the supernumerary ring and giant marker chromosomes containing the chromosomal region 12q14-q15. Dedifferentiated liposarcoma contains a high number of segmental copy number alterations, but has few gene variants.[14]

Myxoid liposarcoma. This entity is characterized by the t(12;16)(q13;p11) translocation that produces the FUS::DDIT3 gene fusion.[14] In a small percentage of cases, EWSR1 substitutes for FUS, producing the EWSR1::DDIT3 gene fusion (t(12;22)(q13;q12)). DDIT3 (previously called CHOP and GADD153) is a stress-induced gene that has an inhibitory effect on adipogenesis.[15] Myxoid liposarcoma is the most common subtype of liposarcoma in the pediatric population. Most pediatric cases show the FUS::DDIT3 gene fusion.[8,9,16]

Pleomorphic liposarcoma. This entity is primarily a disease of older adults and lacks either DDIT3 gene rearrangements or MDM2 amplification. Cases of pleomorphic liposarcoma typically have multiple chromosomal imbalances, including variants in TP53 and NF1 observed in some cases.[17]

Myxoid pleomorphic liposarcoma. This entity most commonly presents in the adolescent and young adult population and lacks the DDIT3 gene rearrangement of myxoid liposarcoma and the MDM2 amplification of atypical lipomatous tumor and dedifferentiated liposarcoma.[9,16,18] Instead, myxoid pleomorphic liposarcoma presents with multiple chromosomal gains and losses. Loss of Rb expression is commonly observed, sometimes in association with loss of chromosome 13q14 where RB1 is located.[18,19] Although most cases of myxoid pleomorphic liposarcoma lack TP53 variants, a minority have TP53 variants that are associated with Li-Fraumeni syndrome in some cases.[20-22]