Myxoid Liposarcoma (MLS) – Causes, Symptoms, Treatment

Myxoid liposarcoma (MLS) is a subtype of liposarcoma that represents a distinct pathological entity characterized morphologically by tumor cells within a myxoid stroma with a rich, branching thin-walled vasculature, and focal lipomatous differentiation.

Myxoid liposarcoma is the second most common subtype (MLs). It accounts for 15–20% of liposarcomas and represents about 5% of all soft tissue sarcomas in adults. Histologically MLS shows a continuous spectrum of lesions with low-grade forms and others poorly differentiated round cell forms [rx]. The tumoral site (upper limb, lower limb, and trunk) did not result in a significant risk factor, even though the few numbers of patients with trunk localization could have hampered statistical significance. It is an important factor of this usually slow-growing, deep-seated tumor mainly located in the lower extremities is the propensity to metastasize to nonpulmonary soft-tissues as the retroperitoneum, the bone, or the contralateral limb [rx]. Furthermore, myxoid liposarcoma is particularly radiosensitive thus neoadjuvant radiation protocols may be very effective [rx–rx].

Causes of Myxoid Liposarcoma

Low grade:

• Atypical lipomatous tumor / well differentiated liposarcoma (ALT / WDL):
  • ALT / WDL can be myxoid and focally indistinguishable from myxoid liposarcoma
  • ALT / WDL usually has some degree of stromal atypia however and will lack the plexiform vasculature
  • ALT / WDL has amplification of chromosome 12q14 (including the MDM2 gene) vs. the FUS rearrangement seen in myxoid liposarcoma
  • Myxoid liposarcomas are also more likely to show a predilection for signet ring lipoblasts
• Extraskeletal myxoid chondrosarcoma (EMC):
  • Composed of cords of epithelioid malignant cells set in a similar chondromyxoid matrix
  • There are no cytoplasmic fat vacuoles and less prominent vasculature
  • Immunohistochemical staining is not helpful (both are S100 positive)
  • Cytogenetics can be helpful but care must be taken
  • EMC have t(9;22)(q22;q12) gene rearrangements in most cases that result in an EWSR1-NR4A3 fusion
  • EWSR1 FISH will be positive but can lead to confusion with the 2 – 5% of myxoid liposarcomas that rarely have EWSR1 rearrangements
  • PCR applications can be particularly helpful in this setting
  • In the lung, primary pulmonary myxoid sarcoma should be considered (Pathology 2017;49:792)
• Lipoblastoma / lipoblastomatosis:
  • Can show similar histology but usually are present in patients less than 5 years old
  • Will have PLAG1 gene rearrangements instead of FUS or EWSR1 rearrangements
• Lipoblastoma-like tumor of the vulva:
  • This is a recently described entity that occurs in the vulva and shares remarkable histologic overlap with lipoblastoma and myxoid liposarcoma
  • These lesions have been shown to have Rb loss like the spindle cell lipoma family of tumors
  • They do not have PLAG1 or FUS rearrangements (Int J Gynecol Pathol 2018 Jan 3 [Epub ahead of print], Am J Surg Pathol 2015;39:1290)
  • There is a significant difference in treatment and clinical outcome (only a limited ability to locally recur) and these lesions should be distinguished wherever possible
• Myxoid dermatofibrosarcoma protuberans (DFSP):
  • Typically these are located superficially, which is uncommon in myxoid liposarcoma
  • Look carefully to distinguish between entrapped fat versus true signet ring lip blasts
  • Immunohistochemical staining and molecular testing can help
  • DFSP will be CD34 positive, S100 negative, with the inverse seen in myxoid liposarcoma and DFSP, will harbor the t(17;22)(q22;q13) COL1A1-PDGFB gene fusion
  • Some large reference labs offer PDGFB as a break-apart FISH assay
• Myxoma:
  • Extremely paucicellular, lacks a prominent vascular component and no lipoblasts are found
  • Associated with GNAS mutations (Mod Pathol 2009;22:718)

High grade:

• Myxofibrosarcoma:
  • Older adults, often superficial, infiltrative and there are no true cytoplasmic fat vacuoles (although they can contain pseudolipoblasts)
  • There is significantly more nuclear atypia, thicker curvilinear vessels and frequent mitotic figures can be found
• Pleomorphic liposarcoma (PLS):
  • The entirely different entity that shares similarity in name only
  • PLS is a high-grade pleomorphic sarcoma with scattered atypical lip blasts
  • Atypia far in excess of what is seen in round cell liposarcoma, which retains its monotony (a clue to a tumor driven by a translocation)
  • PLS typically has a complex karyotype
• Round cell sarcomas (Ewing, BCOR-CCNB3, CIC-DUX4, etc.):
  • There are numerous round cell sarcomas that may morphologically resemble high-grade myxoid liposarcoma
  • Low-grade areas and lip blasts can be particularly informative
  • Immunohistochemical and molecular differences can also be exploited (Ewing sarcoma has different partner genes than does myxoid liposarcoma, a feature that can be taken advantage of via sequencing or PCR)

Symptoms of Myxoid Liposarcoma

Most patients with myxoid liposarcoma have no symptoms until the tumor is large and invades the neighboring organs or tissues, causing tenderness, pain, or functional problems.

Diagnosis of Myxoid Liposarcoma

Treatment of Myxoid Liposarcoma

A standard fraction schedule was used: 2 Gy per fraction, 5 days a week.

Chemotherapy was performed in patients with more than two of these unfavorable prognostic factors: high-grade disease, tumor size > 5 cm, deep sited tumors, and positive surgical margins. Chemotherapy consisted of three or five cycles of epirubicin (60 mg/m2, Days 1-2) and ifosfamide (3 g/m2, Days 1–3) administered every 21 days.

Treatments for liposarcoma include

• Surgery – The goal of surgery is to remove all of the cancer cells. Whenever possible, surgeons work to remove the entire liposarcoma. If a liposarcoma grows to involve nearby organs, removal of the entire liposarcoma may not be possible. In those situations, your doctor may recommend other treatments to shrink the liposarcoma to make it easier to remove during an operation.
• Radiation therapy – Radiation therapy uses powerful energy beams, such as X-rays and protons, to kill cancer cells. Radiation may be used after surgery to kill any cancer cells that remain. Radiation may also be used before surgery to shrink a tumor in order to make it more likely that surgeons can remove the entire tumor.
• Chemotherapy – Chemotherapy uses drugs to kill cancer cells. Not all types of liposarcoma are sensitive to chemotherapy drugs. Careful analysis of your cancer cells by an expert pathologist can determine whether chemotherapy is likely to help you. Chemotherapy may be used after surgery to kill any cancer cells that remain or before surgery to shrink a tumor. Chemotherapy is sometimes combined with radiation therapy.

Newer drugs for

Halaven® (eribulin) and Yondelis® (trabedectin) are approved for people who have not responded to earlier treatment, have widespread liposarcoma, or have cancers that cannot be removed via surgery.

References

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