Soft tissue

Fibroblastic / myofibroblastic

fibrosarcoma

Myxofibrosarcoma



Last author update: 17 May 2022
Last staff update: 17 May 2022

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PubMed Search: Myxofibrosarcoma

Madiha Bilal Qureshi, M.B.B.S.
Nasir Ud Din, M.B.B.S.
Page views in 2021: 27,885
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Cite this page: Qureshi MB, Raza M, Ud Din N. Myxofibrosarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuemyxofibrosarcoma.html. Accessed August 14th, 2022.
Definition / general
  • Myxofibrosarcoma includes a range of malignant fibroblastic tumors with myxoid stroma, variable pleomorphism and characteristic curvilinear vasculature (Surg Oncol Clin N Am 2016;25:775)
Essential features
  • Most common sarcoma of elderly patients
  • Painless, superficial, subcutaneous mass of limbs
  • Multinodular, gelatinous, lobulated tumor with infiltrative margins
  • Spindle to stellate cells in a myxoid stroma with curvilinear vessels and pleomorphic cells
  • Hypercellularity and severe pleomorphism in high grade tumors (Surg Oncol Clin N Am 2016;25:775)
  • Rare epithelioid variant is characterized by nests and sheets of epithelioid cells with focal conventional areas
Terminology
  • Myxoid malignant fibrous histiocytoma (not recommended)
ICD coding
  • ICD-O: 8811/3 - fibromyxosarcoma
  • ICD-10: C49.9 - malignant neoplasm of connective and soft tissue, unspecified
  • ICD-11: 2B53.0 - myxofibrosarcoma, primary site
Epidemiology
  • Affects elderly in the sixth to eighth decades of life (Cancer 2012;118:518)
  • Rare under 30 years
  • Slight male predominance
  • Dermal / subcutaneous location: > 50% of cases
  • Deep / fascial in 33% of cases
Sites
  • Painless, slow growing mass
  • Arises in limbs and limb girdles (lower limb > upper limb) (J Surg Oncol 2021;123:489)
  • Rare on trunk, head and neck, hands and feet
  • Location in body cavities, like abdomen and retroperitoneum, is very rare
    • Most cases of these sites represent dedifferentiated liposarcoma with myxofibrosarcoma-like features
Pathophysiology
  • Complex karyotype with intratumoral heterogeneity and aneuploidy
  • Nondistinct numerical and structural chromosomal abnormalities
  • Higher grade and recurrent tumors show more complex cytogenetic aberrations (Mod Pathol 2006;19:407)
Etiology
  • Unknown
Clinical features
Diagnosis
  • Diagnosis is based primarily on histologic findings in correlation with age, site and clinical features
  • Any undifferentiated pleomorphic sarcoma arising in an extremity of an elderly patient requires thorough sampling to find low grade areas of myxofibrosarcoma
Laboratory
  • Nonspecific
Radiology description
  • CT: low accentuation (AJR Am J Roentgenol 2007;188:W193)
  • MRI:
    • Myxoid component shows low to intermediate signal on T1 weighted images
    • Solid and myxoid components show high signal on T2 / short tau inversion recovery (STIR)
    • Myxoid component does not usually enhance, while the solid component shows enhancement on T1 C+ (Gd)
    • Abnormal signal infiltration along fascial planes (tail sign) (Skeletal Radiol 2013;42:809)
  • Ultrasound: heterogeneous mass, variable presentations (Skeletal Radiol 2022;51:691)
Radiology images

Contributed by Nasir Ud Din, M.B.B.S.
Left shoulder

Left shoulder

Right axillary mass

Right axillary mass



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Infiltrating buttock tumor

Infiltrating buttock tumor

Tail sign

Tail sign

Prognostic factors
  • Prognosis is good when tumor is superficial and low grade
  • Better prognosis than undifferentiated pleomorphic sarcoma
  • Tumor grade affects metastasis and tumor related mortality (30 - 35%) (Anticancer Res 2019;39:2985)
  • Low grade tumors usually do not metastasize (< 5%)
  • High grade tumors have metastatic rate of 20 - 35% (Orthop Traumatol Surg Res 2020;106:1059)
  • The lesser the myxoid area, the poorer the prognosis
  • Epithelioid myxofibrosarcoma is highly aggressive with local recurrence rate of 70% and metastatic rate of 50%
  • Common metastatic sites are lung, intra-abdominal organs and retroperitoneum, also seen in bone and lymph nodes
  • Inadequate surgery leads to local, often repeated recurrence (30 - 40%), irrespective of grade (Ann Surg Oncol 2013;20:80)
  • Tumor grade tends to increase with recurrence
  • Predictors of survival include tumor size, grade and margins (Ann Surg Oncol 2011;18:720)
  • Survival rate, after transformation into an undifferentiated pleomorphic sarcoma-like condition (< 10% myxoid area), approaches that of undifferentiated pleomorphic sarcoma (Am J Surg Pathol 2020;44:87)
  • Immunostain CD44 expression is associated with increased risk of metastasis (Ann Transl Med 2021;9:1322)
  • Immunostain CD109 expression is associated with poor prognosis (J Surg Oncol 2015;111:975)
Case reports
Treatment
Clinical images

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Superficial leg mass

Superficial leg mass

Left leg swelling

Left leg swelling

Gross description
  • Superficial: multinodular with infiltrative margins, usually < 10 cm
  • Cut surface is lobulated, gelatinous and myxoid with gray-white, firm nodules
  • Deep: infiltrative single mass, usually large (Jpn J Clin Oncol 2000;30:458)
  • Hemorrhage and necrosis can be present
Gross images

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Multilobulated mass

Multilobulated mass

Thigh tumor

Thigh tumor

Lower extremity tumor

Lower extremity tumor

Subcutaneous tumor Subcutaneous tumor

Subcutaneous tumor

Frozen section description
  • Usually not performed for diagnostic purpose
  • Used for margin assessment (J Surg Oncol 2021;123:489)
  • Histologic features depend upon the area sampled: low grade versus high grade
  • Atypical spindle cell proliferation (Oral Oncology 2013;49:S123)
  • May show myxoid stroma
Microscopic (histologic) description
  • Lobulated tumor with multinodular growth and incomplete fibrous septae
  • Alternate hypocellular and hypercellular areas
  • 3 tier grading system / FNCLCC grading system used (Oncol Res Treat 2020;43:189)
  • Low grade tumor:
    • Noncohesive, spindle to stellate cells with moderate cytoplasm and atypical, hyperchromatic nuclei
    • Occasional pleomorphic and touton type giant cells
    • Abundant myxoid stroma
    • Elongated, curvilinear blood vessels
    • Perivascular condensation of tumor cells / inflammatory cells (lymphocytes and plasma cells)
    • Pseudolipoblasts (vacuolated fibroblasts) with cytoplasmic mucin and peripherally placed nuclei may be present
    • Infrequent mitoses (Zhonghua Bing Li Xue Za Zhi 2017;46:170)
  • High grade tumor:
    • Cellular fascicles and sheets of spindled to pleomorphic cells with moderate cytoplasm, hyperchromatic nuclei and variable prominent nucleoli
    • Bizarre, multinucleated giant cells with abundant eosinophilic cytoplasm and irregular nuclei
    • Prominent inflammatory infiltrate, more conspicuous at periphery
    • Brisk mitoses with atypical ones, hemorrhage and necrosis
    • Focal conventional low grade areas
  • Intermediate grade tumor:
    • More cellularity and pleomorphism than low grade tumors
    • Lacks solid sheets, marked pleomorphism and necrosis
    • Presence of any hypercellular nonmyxoid area in an otherwise myxoid tumor should be regarded as intermediate grade
  • Epithelioid myxofibrosarcoma (subtype):
    • Predominant atypical epithelioid cells in an otherwise conventional myxofibrosarcoma
    • Cells arranged in nests and sheets
    • Have abundant glassy eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli
    • Diagnosis requires exclusion of carcinoma, melanoma, lymphoma and malignant epithelioid neoplasms as well as presence of conventional myxofibrosarcoma areas, which may be very focal (Am J Surg Pathol 2007;31:99)
Microscopic (histologic) images

Contributed by Nasir Ud Din, M.B.B.S.
Lobulated tumor

Lobulated tumor

Myxoid background

Myxoid background

Curvilinear vessels

Curvilinear vessels

Pleomorphic cells

Pleomorphic cells

Touton type giant cells

Touton type giant cells


Perivascular condensation

Perivascular condensation

Pseudolipoblasts

Pseudolipoblasts

Prominent vacuolation

Prominent vacuolation

Hyperchromatic atypical spindle cells

Hyperchromatic atypical spindle cells

Transition

Transition


Infiltration into skeletal muscle

Infiltration into skeletal muscle

Lobulated cellular tumor

Lobulated cellular tumor

Epithelioid myxofibrosarcoma

Epithelioid myxofibrosarcoma

Epithelioid cells

Epithelioid cells

Cytology description
  • Diagnostic in nearly 65% of cases
  • Spindled cells in a variable amount of myxoid stroma; occasional pleomorphic cells
  • Arborizing capillaries
  • High grade tumor shows pleomorphic and spindled cells in variable myxoid stroma (J Am Soc Cytopathol 2021;10:300)
Cytology images

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Spindle and pleomorphic cells in myxoid matrix

Spindle and pleomorphic cells in myxoid matrix

Positive stains
Electron microscopy description
  • Spindle shaped, fibroblast-like cells: smooth nuclei with abundant parallel membranes and wide cisternae of endoplasmic reticulum
  • Irregular histocyte-like cells: indented nuclei with large nucleoli and coarse chromatin; cytoplasm with conspicuous systems of vesicles and vacuoles
  • Myofibroblast-like cells: abundant cytoplasmic microfilaments with dense body-like structures
  • Occasional cells: intermediate forms and undifferentiated cells
  • Multinucleated tumor cells in high grade tumors (Semin Diagn Pathol 2003;20:72, Ultrastruct Pathol 2013;37:9)
Electron microscopy images

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Ultrastructure of myxofibrosarcoma

Ultrastructure

Distended cisternae with granular material

Distended cisternae with granular material

Molecular / cytogenetics description
  • Somatic copy number alterations:
    • Gains of chromosome 5p
  • Genetic aberrations of p53 signaling and cell cycle G1/S checkpoint:
    • More common: TP53, RB1, CDKN2A / CDKN2B mutations (Sci Rep 2017;7:44700)
    • Less common: CDK6, CCND1, MDM2 amplifications
  • Mutations in components of driver regulomic pathways:
    • NTRK1 mutation and amplification / NF1 alterations in RTK / RAS / MAPK pathway
    • VGLL3 amplification in Hippo pathway
    • TRIO / RICTOR amplifications in RAC / PAK and Akt / mTOR pathways
  • Reference: Mod Pathol 2017;30:1698
Molecular / cytogenetics images

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Genetic analysis

Genetic analysis

Altered genetic pathways

Altered genetic pathways

Videos

Myxofibrosarcoma explained by a sarcoma pathologist

Fibromyxo versus myxofibro sarcoma made simple

Sample pathology report
  • Thigh, wide margin excision:
    • Features are consistent with high grade myxofibrosarcoma, FNCLCC grade 3 (see comment)
    • Tumor size: 8 x 8 x 6 cm
    • Margins:
      • Superior margin: 2 cm
      • Inferior margin: 2 cm
      • Medial margin: 2.1 cm
      • Lateral margin: 2.2 cm
      • Anterior margin: 1.8 cm
      • Posterior margin: 3 cm
    • pTNM stage: pT2, N not assigned
    • Comment: Histology shows a lobulated infiltrative tumor with hypo and hypercellular areas. The hypocellular areas show spindle cells in a myxoid background with curvilinear vessels. The hypercellular areas show fascicles and sheets of moderate to severely pleomorphic, plump spindle to epithelioid cells with interspersed bizarre tumor and touton type giant cells. Brisk mitoses and necrosis are present. Tumor cells show focal SMA and CD34 positivity, whereas desmin, caldesmon, S100 and pancytokeratin are negative. Morphological features and immunoprofile strongly support the diagnosis of high grade myxofibrosarcoma. It is a malignant soft tissue sarcoma with high risk of local recurrence if inadequately excised. Metastatic potential in high grade tumors approaches 20 - 35%.
Differential diagnosis
Board review style question #1

A 55 year old man presented with a painless lump in the left thigh. Gross specimen showed a subcutaneous multinodular tumor of 9 x 8 cm. Histology showed a lobulated and focally infiltrative myxoid tumor with alternating hypo and hypercellular areas. The hypocellular areas showed spindle cells in myxoid stroma with curvilinear blood vessels. The hypercellular areas showed pleomorphic cells in sheets. Brisk mitoses and necrosis were present. Immunostains SMA and CD34 were focal positive and CK AE1 / AE3, caldesmon, STAT6, desmin and S100 were negative. What is the most likely diagnosis?

  1. Cellular myxoma
  2. Malignant peripheral nerve sheath tumor
  3. Myxofibrosarcoma
  4. Myxoid liposarcoma
  5. Myxoinflammatory fibroblastic sarcoma
Board review style answer #1
C. Myxofibrosarcoma

Comment Here

Reference: Myxofibrosarcoma
Board review style question #2

Which vasculature pattern is classic of myxofibrosarcoma?

  1. Chicken wire vessels
  2. Curvilinear vessels
  3. Ectatic vessels
  4. Gaping vessels
  5. Staghorn vessels
Board review style answer #2
B. Curvilinear vessels

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Reference: Myxofibrosarcoma
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