| Subtype | Key defining molecular alteration(s) | Typical anatomic sites | Diagnostic tests used in practice | General clinical behavior | Notable systemic therapies with evidence |
|---|---|---|---|---|---|
| ALT/WDLPS | Amplification of 12q13-15, especially **MDM2** and **CDK4**; **HMGA2** amplification also reported (pqac-00000004, pqac-00000002) | Commonly extremities and retroperitoneum; deep trunk sites also occur (pqac-00000004, pqac-00000005) | MRI/CT for local assessment; core needle biopsy; histopathology with IHC and molecular confirmation of **MDM2/CDK4** amplification, commonly by FISH (pqac-00000004, pqac-00000002, pqac-00000013) | Usually locally aggressive/loco-regional; local recurrence reported in ~30-50%; generally lacks metastatic potential, but a subset dedifferentiates over time (pqac-00000002) | Primarily local therapy; systemic chemotherapy response is poor. Investigational/targeted approaches discussed for MDM2/CDK4-driven disease include CDK4/6 and MDM2 inhibitors (pqac-00000002, pqac-00000007) |
| DDLPS | Shared **MDM2/CDK4** amplification at 12q13-15, often with additional amplifications at **1p32** and **6q23**; higher amplification burden than WDLPS (pqac-00000002, pqac-00000004) | Most commonly retroperitoneum; also deep soft tissues of trunk/extremities (pqac-00000002, pqac-00000004) | CT/MRI; PET/CT may help distinguish WD vs DD components in retroperitoneal/intra-abdominal disease; core needle biopsy; histopathology/IHC; **MDM2/CDK4** molecular testing, commonly FISH (pqac-00000004, pqac-00000002) | More aggressive than WDLPS; ~40% local relapse and ~30% distant metastasis reported; poor outcomes when unresectable (pqac-00000002) | Doxorubicin ± ifosfamide, gemcitabine ± docetaxel, trabectedin, eribulin, pazopanib; activity generally modest/short-lived. Ongoing targeted strategies include CDK4/6 inhibitors, MDM2 inhibitors, and checkpoint inhibitors (pqac-00000002, pqac-00000012, pqac-00000014) |
| Myxoid/round-cell LPS | Usually **FUS::DDIT3**; less commonly **EWSR1::DDIT3** (pqac-00000004, pqac-00000001) | Often proximal lower extremities; may recur/metastasize to retroperitoneum, abdomen, chest, and trunk (pqac-00000007) | MRI/CT; biopsy with histopathology; fusion testing by RT-PCR/FISH/NGS in practice for **DDIT3** rearrangement; molecular confirmation emphasized in subtype classification (pqac-00000004, pqac-00000001) | Higher risk of local and systemic recurrence than WDLPS; can metastasize to extrapulmonary soft-tissue sites; generally more chemosensitive than WDLPS/DDLPS (pqac-00000007, pqac-00000001) | Anthracycline-based chemotherapy has activity; trabectedin is notable, with mechanistic evidence that it detaches FUS-DDIT3 from DNA and restores adipocytic differentiation; eribulin-containing and immunotherapy combinations have reported activity in advanced/retroperitoneal disease (pqac-00000009, pqac-00000008, pqac-00000001) |
| Pleomorphic LPS | Complex karyotype; typically lacks **MDM2/CDK4** amplification; **TP53**, **RB1**, and **NF1** alterations reported in high-grade disease (pqac-00000001, pqac-00000004) | Extremities are common; can arise in deep soft tissues (pqac-00000004) | MRI/CT; biopsy and histopathology; IHC helps exclude MDM2/CDK4-amplified subtypes because these markers are generally negative in PLS (pqac-00000001) | Most aggressive major subtype; local recurrence and metastasis rates reported around 30-50%; metastases often involve lung/pleura; poorer survival than other subtypes (pqac-00000001) | Conventional systemic therapy options are limited and resistance is common; anthracycline-based regimens, eribulin/trabectedin, and investigational immunotherapy/targeted approaches are discussed broadly for advanced liposarcoma, but subtype-specific evidence is limited in the gathered sources (pqac-00000001, pqac-00000012) |
| Myxoid pleomorphic LPS | Distinct entity lacking **FUS/EWSR1::DDIT3** fusions and unlike WDLPS/DDLPS does not show the classic **MDM2/CDK4** amplification pattern; complex genomic changes are described (pqac-00000007) | Not specifically detailed in the gathered evidence (pqac-00000007) | Histopathology with molecular exclusion of DDIT3-rearranged myxoid LPS and MDM2-amplified WDLPS/DDLPS is implied; precise routine testing workflow not detailed in the gathered evidence (pqac-00000007) | Recognized as a distinct aggressive subtype, but recurrence/metastasis rates were not quantified in the gathered evidence (pqac-00000007) | No subtype-specific systemic standard was identified in the gathered evidence; management generally follows sarcoma multidisciplinary practice and clinical trial consideration (pqac-00000007) |


*Table: This table summarizes the major liposarcoma subtypes by defining molecular alterations, typical sites, diagnostic workup, clinical behavior, and systemic therapy evidence. It is useful for quickly comparing how subtype-specific biology drives diagnosis and treatment selection.*