[4] However, the liposarcomas do have several forms based on differences in their clinical presentations (e.g. ages, gender preferences, sites of tumors, signs, and symptoms), severities (i.e. potential to invade local tissues, recur after surgical removal, and metastasize to distal tissues), genetic abnormalities, prognoses, and preferred treatment regimens.

Studies to date find that all five liposarcoma forms, while usually treatable at least initially by surgical resection, are often only marginally responsive to currently used chemotherapy and radiotherapy regimens.

The liposarcomas require a wide range of further studies to determine their responsiveness to various radiotherapy, chemotherapy, and more novel treatment regimens as used individually and in various combinations that would include, where possible, surgical removal.

[6] ALT and WDL (hereafter termed ALT/WDL) tumors typically present in middle-aged and older individuals as slowly enlarging masses that tend to be larger and at a more advanced stage when located in deep tissues.

Adipocytic/lipoma-like ALT/WDL tumors consist of lobules of mature fat cells variably intersected with irregular fibrous septa (see the adjacent H&E stained photomicrograph).

In particular, detection in the ALT/WDL tumor cells of an overexpressed MDM2 or CDK4 gene or the presence of either the specific ALT/WDL-associated sSMC or giant marker chromosome (as defined by next generation DNA sequencing, comparative genomic hybridization,[18] and/or highly specialized cytogenetic G banding analyses[19]) strongly supports the diagnosis of ALT/WDL or dedifferentiated liposarcoma.

These less surgically assessible tumors tend to recur repeatedly and ultimately may cause death due to their injurious effects on vital organs.

Individuals with a de novo diagnosis of this tumor may have had an ALT/WDL that progressed to a dedifferentiated liposarcoma but went undetected because it developed asymptomatically in a highly sequestered site such as the retroperitoneum or abdominal cavity.

[8] Dedifferentiated lipoosarcomas (DDL) occur most frequently in middle-aged and older adults with a peak incidence in their sixth to eighth decades.

[21] At presentation, DDL tumors typically are painless, large, may have been slowly and progressively enlarging for years,[8] and on routine X-rays contain areas of calcium deposition (exemplified by Fig.

The signs and symptoms of chronic inflammation and the various paraneoplastic syndromes are caused by the tumors' secretion of cytokines, hormones, prostaglandins, and/or other systemically acting agents; they completely disappear after the DDL is successfully treated.

[12][17] Overexpression of the MDM2 and CDK genes, and/or other genetic material in the sSMCs or giant marker chromosomes are suspected of promoting the development and/or progression of DDL as well as ALT/WDL tumors.

[8] Alternately, detection in the tumor cells of an overexpressed CDK4 gene or the presence of either the specific ALT/WDL-associated sSMCs or giant marker chromosome strongly support the diagnosis of DDL or ALT/WDL.

[6] However, emerging studies suggest that patients with DDL tumors that are restricted to an extremity or the trunk and have a predicted 10-year tumor-related overall survival of 51% or less have improved outcomes when chemotherapy (e.g. doxorubicin plus ifosfamide) is added to their surgical regimens.

Preliminary analysis showed that this inhibitor of the CDK4 and CDK6 genes' product Serine/threonine-specific protein kinase enzymes produced a prolonged median progression-free survival time of 30.4 weeks.

[35] A phase III registration study (i.e. a large confirmatory study meant to establish an acceptable benefit/safety profile in order to gain regulatory approval for a precisely defined indication) is evaluating the safety and efficacy of milademetan compared to trabectedin in patients with unresectable (i.e., resection is deemed to cause unacceptable morbidity or mortality) or metastatic DDL that has progressed on 1 or more prior systemic therapies, including at least 1 anthracycline-based therapy.

[36] Another phase III clinical trial is investigating the MDM2 inhibitor milademetan[37] versus trabectedin, a blocker of the oncogenic transcription factor FUS-CHOP, in MDM2-overexpressing ALT/WDL and DDL.

In about one-third of cases, these tumors metastasize to other soft tissue sites (e.g. retroperitoneum, thorax, or other extremity), skeletal bone, and/or lung.

[6] Low-grade and intermediate-grade MLS tumors can be identified histologically by their classic morphology of distinctive chicken-wire vasculature scattered throughout a myxoid stroma.

Other factors that have been associated with unfavorable outcomes in MLS include presence of tumor necrosis, age >45 years, P53 gene overexpression,[40] and male gender.

[48] A stage II clinical trial conducted in Italy is examining the effects of a trabectedin plus pioglitazone (another PPAR-γ agonist) in individuals with stable MLS tumors.

If stable disease is attained, the second step will examine the effects of further treating initially responding patients with a combination of trabectedin and pioglitazone.

[56] Rare cases of PLS have presented in individuals with the Li-Fraumeni or Muir–Torre syndromes, two hereditary genetic disorders that predispose affected persons to develop various types of cancer.

[58] Radical surgical resection is the main treatment for PLS; it is also an important palliative intervention to relieve symptoms due to the compression of organs and tissues.

[55] The National Comprehensive Cancer Network recommends treatment for individuals with high-risk localized PLS by complete surgical resection, when feasible, combined with radiation therapy.

Tumors located in the center position of the trunk, larger than 10 cm in size, deeply seated, or containing areas of necrosis have worse prognoses.

[62] MPL tumors present as deep soft-tissue masses that are often located in the mediastinum[44] and, less often, the extremities, head and neck, abdominal cavity, or trunk.

[62] The diagnosis of MPL depends on its tumors clinical presentation, histopathological resemblance to myxoid liposarcoma, and, most critically, absence of the FUS-DDIT3 sn EWSR1-DDIT3 fusion genes in its neoplastic cells.

[6] Medical ultrasonography and magnetic resonance imaging (MRI) of liposarcomas are helpful and often essential in determining their extent, surgical accessibility, and relationship to any observed organ dysfunctions.

Since ultrasonography is usually unable to distinguish a liposarcoma from a benign lipoma, MRI is the initial imaging of choice to provide evidence relative to making this distinction.