Liposarcoma

What is liposarcoma?

Liposarcoma (LPS), one of the most common forms of soft tissue sarcoma, is a malignant neoplasm of adipocyte (fat cell) differentiation. It predominantly arises in the deep soft tissue of the extremities and retroperitoneum; less commonly, it can occur in the subcutaneous tissue.

LPS can be subcategorised according to various factors, including histology, molecular profile, location, and growth pattern.

According to the WHO 2020 classification, subcategories are:

• Well-differentiated liposarcoma/atypical lipomatous tumour (WDLPS/ALT)
• Dedifferentiated liposarcoma (DDLPS)
• Myxoid liposarcoma (MLPS)
• Pleomorphic liposarcoma (PLPS)
• Myxoid pleomorphic liposarcoma (MPLPS)

Subtypes behave variably with regard to local recurrence, metastatic potential, responsiveness to different treatment modalities, and prognosis.

Who gets liposarcoma?

LPS is a heterogeneous group of soft tissue tumours, accounting for 15-20% of all soft tissue sarcomas. Incidence is approximately 0.4-1.1 cases per 100,000 person-years. Overall, LPS tends to occur in middle-aged to older adults, however this varies according to subtype.

What causes liposarcoma?

LPS arises de novo rather than from a pre-existing lipoma. Unlike other soft tissue sarcomas, radiation does not appear to play a role in pathogenesis.

The genetics of LPS vary based on the type of liposarcoma:

• WDLPS and DDLPS: characterised by recurrent amplifications within chromosome 12, resulting in over-expression of oncogenic genes;
• MLPS is characterised by a pathognomonic chromosomal translocation between chromosomes 12 and 16, resulting in an oncogenic fusion protein (FUS-DDIT3)
• PLPS is karyotypically complex, with a variety of mutations present.

What are the clinical features of liposarcoma?

LPS most commonly presents as a painless mass; primary lesions are polypoid, non-tender masses ranging from 1 to 19.5 cm. If LPS is found in the subcutaneous tissue, it is usually due to extension from the deep soft tissues. In the case of retroperitoneal disease, patients may present with diffuse abdominal distension or abdominal pain.

LPS of an extremity may present as a large, deep mass with pain or swelling of the involved limb due to local compression of neurovascular structures or bleeding into the tumour.

What are the complications of liposarcoma?

• Localised compression of adjacent organs/vessels/nerves +/- upper gastrointestinal bleeding
• Metastatic spread to other organs
• Death

How is liposarcoma diagnosed/staged?

• Physical examination
• Biopsy is required to formally diagnose LPS and to subtype for planning treatment; see liposarcoma pathology
• If an extremity is involved, X-ray to evaluate for bony involvement and soft tissue calcifications
  MRI with and without contrast shows heterogeneous signal intensity/hypointensity compared to surrounding muscle on T1 sequences and hyperintensity on T2 sequences
• For staging, CT chest (the most common site of metastasis) +/- CT/MRI of the abdomen, pelvis, and/or spine (depending on tumour location)

What is the differential diagnosis for liposarcoma?

• Lipoma
• Pleomorphic lipoma
• Lipoblastoma
• Lipoblastomatosis
• Other forms of soft tissue sarcoma

What is the treatment for liposarcoma?

• Referral to a multidisciplinary treatment centre
• Radical surgical resection with wide local excision for localised/resectable disease
• Radiotherapy for deep-seated, high-grade LPS of the extremities (neoadjuvant or adjuvant)
• Chemotherapy is the first-line therapy for metastatic/unresectable disease. Although LPS as a group is relatively insensitive to chemotherapy, the hypercellular, round cell variant of MLPS tends to the most chemotherapy-sensitive form of LPS; therefore, chemotherapy may be considered as neoadjuvant treatment before resection in this subtype
• Targeted therapies may be considered for 1st or 2nd line treatment failure

How do you prevent liposarcoma?

There are no well-established modifiable risk factors for LPS.

What is the outcome for liposarcoma?

WDLPS/ALT is considered a low-grade tumour and, as such, has the most favourable prognosis. MLPS has an intermediate prognosis, and PLPS carries the worst prognosis.