Soft tissue
Adipose tissue
Myxoid liposarcoma

Author: Michael Clay, M.D. (see Authors page)

Revised: 30 January 2018, last major update January 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Myxoid liposarcoma[TI] soft tissue[TIAB]

Cite this page: Clay, M. Myxoid liposarcoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/softtissuemyxoidliposarcoma.html. Accessed December 15th, 2018.
Definition / general
  • Malignant tumor composed of primitive nonlipogenic mesenchymal cells, signet ring lipoblasts and prominent myxoid stroma with a highly characteristic branching vascular pattern
Essential features
  • Prominent myxoid stroma with branching vasculature (so called chicken wire vasculature)
    • Majority of the tumor can be nonlipogenic with only scattered lipoblasts that often have a characteristic signet ring morphology
  • Recurrent molecular alteration with either t(12;16)(q13;p11.2) FUS-DDIT3 or very rarely (~2%) t(12;22)(q13;q12) EWSR1-DDIT3 rearrangements
  • Includes a spectrum of disease including high grade lesions, which were formerly regarded as "round cell liposarcoma" (see terminology below)
  • Has an unusual propensity to present with a first metastasis to another soft tissue or bony site (such as from one leg to the contralateral leg or to the retroperitoneum or spine)
Terminology
  • Although myxoid liposarcoma and round cell liposarcoma were initially described separately, both tumors have identical molecular alterations and clear evidence of cases with transition between the two morphologic patterns are easily found
    • Both tumors are now classified as "myxoid liposarcoma" with a secondary designation of high or low grade
  • Percent of round cell component needed for this distinction is debated in the literature with most pathologists using either > 25% or > 5% indicating a high grade lesion
  • Cases with borderline round cell component (< 5%) are regarded as having areas of "transition," a designation of unclear diagnostic significance
Epidemiology
  • Peaks in the fourth and fifth decades and represents ~5% of adult sarcomas
  • No gender predilection
  • May occur in children or very rarely in the elderly
Sites
  • Usually in the extremity, proximal thigh is quite common
  • Primary retroperitoneal involvement is rare, although metastasis to the retroperitoneal soft tissue is not uncommon
  • Propensity to present with multifocal disease, seemingly from hematogenous spread that has spared the lungs (J Surg Oncol 2002;80:89)
  • Primary subcutaneous tumors have been reported (J Cutan Pathol 2014;41:907)
Case reports and relevant reviews
Prognosis and treatment
  • Predilection for metastasis, especially when there is a significant round cell component
  • Metastases can occur decades later, necessitating continued long term follow up (World J Surg Oncol 2008;6:62)
  • Pure low grade tumors have less aggressive behavior but still share a propensity for recurrence and can metastasize in 5 - 10% of cases
  • Unfavorable outcome has been associated with TP53 and CDKN2A gene mutations, although this seems rare (Tumori 1998;84:571)
  • Some evidence that high grade components can be identified via MRI (Acta Radiol 2014;55:952) and that metastases can be identified very early with imaging studies (Skeletal Radiol 2018;47:369)
Gross description
  • Typically these lesions are well circumscribed and multinodular
  • Low grade tumors will have a gelatinous cut surface, with higher grade tumors showing more solid fleshy appearance
Gross images

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Well differentiated myxoid liposarcoma

Thigh tumor postchemotherapy



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Recurrence of adipose mass with kidney involvement

Well circumscribed white tumor

Lobulated gray white tumor within skeletal muscle

Microscopic (histologic) description
Low grade:
  • Paucicellular with monomorphic, stellate or fusiform shaped cells without atypia; striking in their blandness, so much so that any significant pleomorphism should cause one to pause
  • Prominent plexiform vasculature (delicate thin walled arborizing and curving capillaries that form a network reminiscent of chicken wire fencing)
    • These are so striking because of the overall background paucicellularity and are still present but much less obvious in high grade tumors
  • Numerous signet ring lipoblasts, particularly at periphery of lobules
  • Mucoid matrix is rich in hyaluronic acid that may form large mucoid pools (so called pulmonary edema pattern)
    • Will be positive for stromal mucin stains such as Alcian blue (see microscopic images below)
  • Rarely metaplastic cartilage or bone can be seen
  • Typically there is no significant mitotic activity
  • There are many rare morphologic variants; an excellent review of the spectrum of histologic features can be found at Am J Clin Pathol 2012;137:229

High grade:
  • Hypercellular solid sheets of back to back cells with round cell or primitive cytomorphology in greater than 5% of the sampled tumor
  • Cells can have a small amount of hypereosinophilic cytoplasm, a finding of no clinical significance but of significant diagnostic confusion, especially in a limited sample

Pitfalls and tips:
  • Round cell features of high grade tumors are so cellular you can typically "walk" across nuclei in a high power field without "stepping" in matrix
  • When in doubt, especially in a small sample, pursue molecular testing (typically fluorescent in situ hybridization) for FUS gene rearrangement
    • If you are particularly certain and FUS is negative, proceed to EWSR1
  • Sample these tumors extensively; you likely will not see small amounts of round cell progression grossly
  • Can contain large areas of mature adipocytic differentiation
    • If the clinical or radiologic picture is concerning, sample additional tumor or do molecular testing
  • Location (extremity) and age of the patient (young adult) can be helpful clues in the differential diagnosis
  • Most of the diagnostic clues are helpful in the appropriate context but individually can be seen in many other tumor types
    • Plexiform vasculature and cells that look like signet rings can be found in a diverse variety of tumors
    • Combination of a number of clinical, radiologic, histologic and if needed, molecular features will make the diagnosis
Microscopic (histologic) images

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Images hosted on PathOut server:

Images contributed by Dr. Jesse J. Jenkins:

Bland stellate shaped cells

High power

Pulmonary edema pattern

Signet ring lipoblasts


Alcian blue special staining

S100 protein immunostaining

Vimentin immunostaining



AFIP images:

High grade myxoid liposarcoma with sheets of primitive round cells

Postchemotherapy


Low grade myxoid liposarcoma showing delicate capillary network

Cords of cells resembling myxoid chondrosarcoma

Hyalinized collagenous stroma (rare finding)


Low grade myxoid liposarcoma with the pulmonary edema pattern, so named because the irregular cystic spaces resemble alveolar spaces at low power

Large (mature) and small fat cells


Hypocellular zones: left - small artery, middle - veins, right - transition between cellular and hypocellular areas

Signet ring lipoblasts



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Round cell liposarcoma

Branched capillaries in a myxoid stroma

Alcian blue mucin stain


Lipoblasts, myxoid stroma and branched capillaries

Lipoblasts, myxoid stroma and branched capillaries


Lipoblasts

Metastases

Cytology description
Negative stains
Molecular / cytogenetics description
  • t(12;16)(q13;p11.2) FUS-DDIT3 in most cases
  • t(12;22)(q13;q12) EWSR1-DDIT3 very rarely (2 - 5%)
  • Rearrangements can be complex and involve other chromosomes (Am J Clin Pathol 1995;103:20)
  • DDIT3 was formerly known as CHOP (early literature will use the terminology FUS-CHOP)
  • Can be identified via FISH, PCR, classic cytogenetics and sequencing means
Differential diagnosis
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 lipoblasts
    • 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):
    • Entirely different entity that shares similarity in name only
    • PLS is a high grade pleomorphic sarcoma with scattered atypical lipoblasts
    • 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 lipoblasts 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)
Board review question #1
Which of the following features is not associated with low grade myxoid liposarcomas?

  1. Absence of nuclear atypia
  2. Arborizing plexiform vasculature
  3. EWSR1 gene rearrangement
  4. Primary tumor in the retroperitoneum
  5. Propensity to "skip" the lung and metastasize to other soft tissue sites
Board review answer #1
D. Primary tumor in the retroperitoneum. Although they can commonly metastasize to the retroperitoneum, primary retroperitoneal tumors are quite rare. Remember, up to 5% of these tumors can have alternative EWSR1 gene rearrangements.