Soft tissue
Fibroblastic / myofibroblastic
Fibrosarcoma
Myxofibrosarcoma
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Last author update: 17 May 2022
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PubMed Search: Myxofibrosarcoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Qureshi MB, Raza M, Ud Din N. Myxofibrosarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuemyxofibrosarcoma.html. Accessed April 18th, 2024.
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
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
- Slow growing, painless mass
- Rare clinical presentations include erosive inflammatory arthritis, acute carpal tunnel syndrome, pulmonary thromboembolism, etc. (Skeletal Radiol 2019;48:1643, J Hand Surg Am 2008;33:269, J Thorac Dis 2017;9:E1084)
- Increased risk of development in Werner syndrome
- Association with Muir-Torre syndrome (Hered Cancer Clin Pract 2021;19:34)
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
Right axillary mass
Images hosted on other servers:
Infiltrating buttock tumor
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
- 34 year old woman presented with dyspnea and chest pain for half a month (BMC Cancer 2018;18:512)
- 37 year old woman presented with painful progressive swelling in the preauricular area (BMC Cancer 2010;10:246)
- 45 year old woman presented with a slow growing mass of right soft palate (Head Neck Pathol 2021;15:1372)
- 51 year old woman presented with a painless, mobile gingival swelling (BMC Oral Health 2020;20:113)
- 62 year old man developed 2 histologically distinct sarcomas (Int J Surg Pathol 2015;23:149)
- 70 year old woman with recurrent right upper eyelid swelling (BMC Ophthalmol 2020;20:264)
- 70 year old woman with a large mass in right kidney (Pathol Res Pract 2015;211:619)
Treatment
- Complete surgical excision with negative margins: 2 cm margin of surrounding normal tissue / fascial plane / periosteum (Surg Oncol Clin N Am 2016;25:775)
- Adjuvant radiotherapy for local control (Sarcoma 2019;2019:8517371)
- Staged resection and reconstruction for local control (Eur J Surg Oncol 2021;47:2627)
- Role of chemotherapy and targeted therapy is under investigation (Clin Sarcoma Res 2017;7:16, Curr Oncol 2021;28:813, Medicine (Baltimore) 2021;100:e25262, Mol Clin Oncol 2020;13:54)
Clinical images
Images hosted on other servers:
Superficial leg mass
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
Images hosted on other servers:
Multilobulated mass
Thigh tumor
Lower extremity 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
Myxoid background
Curvilinear vessels
Pleomorphic cells
Touton type giant cells
Perivascular condensation
Pseudolipoblasts
Prominent vacuolation
Hyperchromatic atypical spindle cells
Transition
Infiltration into skeletal muscle
Lobulated cellular tumor
Epithelioid myxofibrosarcoma
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
Images hosted on other servers:
Spindle and pleomorphic cells in myxoid matrix
Positive stains
- Immunohistochemistry is not specific; done in order to exclude other sarcomas:
- Vimentin
- SMA: focal (Am J Surg Pathol 1996;20:391)
- MSA: focal
- CD34: focal
Negative 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
Images hosted on other servers:
Ultrastructure
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
Images hosted on other servers:
Genetic analysis
Altered genetic pathways
Videos
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
- Low grade myxofibrosarcoma:
- Low grade fibromyxoid stroma:
- Occurs in young adults
- Proximal extremities and trunk are the most common sites
- Mostly subfascial; superficial location in pediatric population (Am J Surg Pathol 2005;29:204)
- Collagenous hypocellular areas with cellular myxoid nodules
- Arcading vessels with perivascular sclerosis
- Low mitotic index
- EMA and MUC4 positive
- FUS-CREB3L2 gene fusion
- See video above
- Intramuscular cellular myxoma:
- Deep location
- Occurs in middle aged adults
- Mitotic activity is low; no nuclear atypia, hyperchromasia or necrosis
- Point mutation in GNAS (J Cell Mol Med 2009;13:1291)
- Myxoid neurofibroma:
- Dermal nerve sheath myxoma:
- Superficial angiomyxoma:
- Affects head and neck, trunk and genital area
- Occurs in children and adults
- Multilobulated growth pattern in dermis and subcutis
- Bland spindle to stellate cells in a myxoid stroma
- Thin walled vessels with focal arborizing pattern
- Stromal neutrophils in 50% of cases
- Epithelial proliferation related to hair follicle (Am J Dermatopathol 2003;25:281)
- Myxoid dermatofibrosarcoma protuberans (DFSP):
- Occurs in young adults
- Honeycomb pattern of infiltration
- Focal classic DFSP areas
- CD34 positive
- COL1A1-PDGFB fusion (Am J Surg Pathol 2007;31:1371)
- Nodular fasciitis:
- Occurs in young adults
- Rapidly growing mass
- Plump spindle cells, increased mitoses
- May have cellular nonmyxoid and tissue culture-like areas
- Extravasation of red blood cells
- Numerous small vessels
- USP6 rearrangement (Virchows Arch 2018;473:351)
- Myxoid liposarcoma:
- Deep location
- Adults affected; can be seen in children
- Ovoid cells with signet ring lipoblasts
- Chicken wire-like plexiform vasculature
- Extracellular mucin pools (microcystic pattern)
- Atypia absent
- FUS-DDIT3 or EWSR1-DDIT3 gene fusion (Virchows Arch 2001;438:13)
- Low grade fibromyxoid stroma:
- Intermediate / high grade myxofibrosarcoma:
- Malignant peripheral nerve sheath tumor:
- Dedifferentiated liposarcoma:
- Occurs in middle age adults
- More common in retroperitoneum
- May have well differentiated liposarcoma component
- CDK4 and MDM2 positive
- MDM2 amplification (Histopathology 2013;62:287)
- Undifferentiated pleomorphic sarcoma:
- Deep location
- Lacks low grade areas of myxofibrosarcoma
- Lineage specific soft tissue sarcoma immunomarkers are usually negative (J Clin Oncol 2018;36:160)
- Myxoinflammatory fibroblastic sarcoma:
- Rare tumor with wide age range
- Occurs in acral dorsal extremities
- Sheets and scattered foci of epithelioid to spindle cells
- Reed-Stenberg-like cells with prominent nucleoli
- Atypia present but mitoses is low
- Dense inflammation with myxohyaline stroma (Arch Pathol Lab Med 2014;138:1406)
- Epithelioid myxofibrosarcoma:
- Pleomorphic liposarcoma:
- Rapidly growing
- Undifferentiated pleomorphic sarcoma with pleomorphic multivacuolated lipoblasts
- May have myxofibrosarcoma-like areas
- Pleomorphic rhabdomyosarcoma:
- Anaplastic large cell lymphoma:
- Melanoma:
- Carcinoma:
- Keratins positive (Zhonghua Bing Li Xue Za Zhi 2016;45:10)
- Pleomorphic liposarcoma:
Additional references
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?
- Cellular myxoma
- Malignant peripheral nerve sheath tumor
- Myxofibrosarcoma
- Myxoid liposarcoma
- Myxoinflammatory fibroblastic sarcoma
Board review style answer #1
Board review style question #2
Which vasculature pattern is classic of myxofibrosarcoma?
- Chicken wire vessels
- Curvilinear vessels
- Ectatic vessels
- Gaping vessels
- Staghorn vessels
Board review style answer #2
