Knowledge on rare diseases and orphan drugs

The incidence is approximately 1/769, 000 per year and it accounts for 30% or less of all LS cases.

MRCLS presents at a younger age than other LS subtypes with typical age of diagnosis ranging from 35-55 years. It predominantly occurs in the limbs (most frequently in the thighs) and rarely arises in the retroperitoneum or subcutaneous tissue. One third of MRCLS cases will become metastatic with tumors spreading to unusual bone and soft tissue locations with multifocal synchronous or metachronous spread to fat pad areas in the retroperitoneum, trunk, pericardium and axilla.

Ninety percent of MRCLS lesions have a characteristic chromosomal translocation leading to the fusion of the DDIT3 and FUS genes on chromosome regions 12q13 and 16p11. The consequence is the creation of a FUS-DDIT3 hybrid protein that promotes malignant transformation by dysregulating RNA transcription and thereby dysregulating adipocyte differentiation and cell-cycle control.

When a mass is detected, computed tomography (CT) or magnetic resonance imaging (MRI) is performed. Chest and abdominal lesions do not require pretreatment biopsy unless resection is likely to be incomplete or highly morbid. Extremity lesions are generally sampled by multiple core biopsies to identify the histological subtype (myxoid versus round cell component) and to stage the disease. MRCLS tumors are composed of uniform, round to oval, primitive nonlipogenic mesenchymal cells and small signet-ring lipoblasts in a prominent myxoid stroma with plexiform vasculature. The diagnosis can be confirmed by evidence of the DDIT3-FUS translocation from fluorescence in situ hybridization (FISH) or RT-PCR. High levels of the round cell component predict a poorer outcome, so it must be determined whether the tumor is more myxoid (<5% round cell component) or round cell (>5% round cell component).

MRCLS can be mistaken for Ewing sarcoma, lymphoma and pleomorphic undifferentiated sarcomas (see these terms). Other myxoid neoplasms must also be excluded.

Treatment involves the surgical excision of the tumor and surrounding tissue for low grade myxoid liposarcoma. In rare cases amputation of the limb is necessary. High grade round cell LS that is large (>5 cm), or marginally resectable tumors, may be treated with pre-operative chemotherapy and/or pre-operative or post-operative radiotherapy. MRCLS, compared to other subtypes, responds well to radiotherapy and chemotherapy. Chemotherapeutic agents doxorubicin and ifosfamide are usually first line treatment options whereas ecteinascidin is used as a second line treatment. Lifelong follow-up is recommended in order to monitor for recurrence at the initial site as well as distant metastasis.

The prognosis of MRCLS is good for patients with low grade myxoid liposarcoma (defined as pure myxoid or less than a 5% round cell component), the 5-year survival rate is 92%. A significant (5% or greater) round cell component is associated with a much poorer prognosis, with a 5-year survival rate of 74%.

Last update: January 2013 - Expert reviewer(s): Dr Samuel SINGER