Soft tissue

Uncertain differentiation

Epithelioid sarcoma

Editor-in-Chief: Debra L. Zynger, M.D.
Farres Obeidin, M.D.
Borislav A. Alexiev, M.D.

Last author update: 30 March 2020
Last staff update: 25 July 2023

Copyright: 2002-2024,, Inc.

PubMed Search: Epithelioid sarcoma [title] Soft tissue free full text[sb]

Farres Obeidin, M.D.
Borislav A. Alexiev, M.D.
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Cite this page: Obeidin F, Alexiev B. Epithelioid sarcoma. website. Accessed April 14th, 2024.
Definition / general
  • A malignant mesenchymal neoplasm that exhibits epithelioid cytomorphology and a predominantly epithelial phenotype
Essential features
  • Malignant epithelioid tumor occurring in pediatric and adult populations
  • Unpredictable clinical course; better prognosis in pediatric patients
  • Two typical morphologies, including classic type with epithelioid to spindled cells with central pseudogranulomatous architecture; and proximal type with predominant epithelioid and rhabdoid cells
  • IHC: Pancytokeratin+, INI1 lost
  • Molecular: Mutations in INI1/SMARCB1
  • Classic or conventional type is also known as distal type
  • Proximal type is also known as large cell type
  • Defunct name: sarcoma aponeuroticum
ICD coding
  • ICD-10: C49.0 - malignant neoplasm of other connective and soft tissue
  • ICD-O: 8804/3 - epithelioid sarcoma
  • Rare, < 1% of all adult soft tissue sarcomas, 4 - 8% of pediatric non rhabdomyoblastic sarcomas
  • Classic type epithelioid sarcoma is more common than the proximal type epithelioid sarcoma
  • Classic type: Most common in adolescents and young adults, between ages 10 and 40 years; M:F = 1.9:1 (Adv Anat Pathol 2016;23:41)
  • Proximal type: Middle aged to older adults, > 80% presenting between ages of 20 and 65 years; M:F = 1.6:1
  • Either type may arise anywhere
  • Classic type: usually distal upper extremity, > 60% arising in the fingers and hand
  • Proximal type: more common in deep soft tissue, truncal tissue (including pelvic peritoneal, genital and inguinal) and buttock / hip
Clinical features
  • Solitary or multiple, slowly growing, usually painless, firm nodules (J Clin Aesthet Dermatol 2009;2:49)
  • Lesion often results in non healing skin ulcers that have a tendency to clinically mimic other ulcerative dermal processes
  • Core needle biopsy for deep tumors and punch biopsy for dermal tumors
  • Followed by wide resection
Radiology description
  • No distinct MR imaging characteristic of this tumor that would enable early specific diagnosis
  • Tumors may show variable amounts of fibrosis, granulomatous pattern, necrosis and cellularity, corresponding to variable T2-weighted signal; T1-weighted images usually isointense to muscle but may have variability due to hemorrhage or necrosis
  • Suspicion should arise when presenting with multiple soft tissue nodules or persistent punched out ulcers involving the skin and subcutaneous tissues (Skeletal Radiol 2002;31:400)
Radiology images

Contributed by Borislav Alexiev, M.D.
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T2-weighted MRI, hand

Prognostic factors
  • Course is often unpredictable; common to present with extensive disease, lymph node metastases or distant metastases (J Clin Aesthet Dermatol 2009;2:49)
  • Adverse prognostic factors include proximal site, large size, male sex, older age, necrosis, vascular invasion, rhabdoid cytomorphology and inadequate excision (Adv Anat Pathol 2016;23:41, Adv Anat Pathol 2006;13:114)
  • In adults: 5 year overall survival of 50 - 85%
  • In pediatric population: better prognosis; 5 year overall survival of 92.4%, more likely to have localized, classic type morphology, fewer nodal or distant metastases at presentation (Adv Anat Pathol 2016;23:41)
  • Proximal epithelioid sarcoma is an aggressive tumor; 65% of patients die of disease (Mod Pathol 2001;14:655)
Case reports
Clinical images

Contributed by Mark R. Wick, M.D.
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Gross description
  • Classic subtype usually presents as one or more indurated, ill defined, dermal or subcutaneous nodules (Cancer 1970;26:1029)
  • Deep seated tumors are multinodular masses and involve tendons or fascia
  • Cut surface is glistening with gray-white or gray-tan color and multiple areas of hemorrhage and necrosis (Arch Pathol Lab Med 2009;133:814)
Gross images

Contributed by Borislav Alexiev, M.D.
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Mass in subcutis

Microscopic (histologic) description
  • Classic and proximal epithelioid sarcoma can each occur in either proximal or distal sites and may show features of both types (Histopathology 2001;39:641)
  • Classic or conventional, distal type (Adv Anat Pathol 2006;13:114)
    • Dermal / subcutaneous nodule(s)
    • Can simulate granulomatous process, with or without necrosis (pseudogranulomatous morphology)
    • Fairly uniform plump small to medium sized cells with eosinophilic cytoplasm (Adv Anat Pathol 2016;23:41)
    • Spindle cells can also be identified and often appear more conspicuous at the periphery of a nodule
    • Mildly atypical nuclei with vesicular chromatin and small nucleoli
    • Variable mitotic activity
    • Mixed chronic inflammatory infiltrate common
    • Dystrophic calcification and metaplastic bone formation
    • Other variant morphologies (Adv Anat Pathol 2016;23:41)
      • Angiomatoid variant
      • Myxoid variant
      • Other features include intracytoplasmic vacuoles, multinucleated giant cells and storiform pattern
  • Proximal, large cell type (Am J Surg Pathol 1997;21:130, Adv Anat Pathol 2016;23:41)
    • Infiltrative growth pattern with less defined peripheral borders
    • Multiple large nodules
    • Large polygonal cells with abundant eosinophilic cytoplasm
    • Rhabdoid morphology common
    • Vesicular nuclei with prominent macronucleoli
    • Mitoses, necrosis and hemorrhage common
Microscopic (histologic) images

Contributed by Borislav Alexiev, M.D.
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Soft tissue neoplasm

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Pseudo-granulomatous morphology

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Epithelioid morphology

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Mild nuclear atypia

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Pleomorphic epithelioid cells

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Rhabdoid morphology

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Pancytokeratin AE1/AE3 expression

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CD34 expression

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INI1 expression

Virtual slides

Images hosted on other servers:
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Epithelioid sarcoma, distal type

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Epithelioid sarcoma, proximal type

Cytology description
  • Smears in most cases were moderate to hypercellular, composed of polygonal cells and spindle cells
  • Cells are arranged in loosely cohesive groups, non overlapping clusters and scattered singly, containing moderate to abundant cytoplasm, defined cell borders, vesicular nuclei and discernible nucleoli
  • Variable cytopathologic features include rhabdoid-like intracytoplasmic inclusions, giant cells, marked nuclear atypia and interspersed scanty, metachromatic stroma (Diagn Cytopathol 2016;44:636)
  • Necrotic and inflammatory background (Cancer Cytopathol 2018;126:934)
Positive stains
Negative stains
Electron microscopy description
  • Shows a spectrum of cellular differentiation, from undifferentiated cells or primitive fibrohistiocytic cells to epithelial type cells with junctions, tonofilaments and microvilli (Hum Pathol 1988;19:265)
  • Other findings have included desmosomes, surface microprocesses and interdigitating cell membranes, indicating epithelial (sometimes interpreted as synovial sarcoma-like) differentiation (Adv Anat Pathol 2006;13:114)
  • Proximal epithelioid sarcoma often shows prominent intracytoplasmic intermediate filament aggregates that often take the shape of paranuclear whorls in keeping with the rhabdoid phenotype (Adv Anat Pathol 2016;23:41)
Molecular / cytogenetics description
Sample pathology report
  • Right hand mass, excision:
    • Epithelioid sarcoma, classic type (see comment)
    • Comment: There is a dermal and subcutaneous multinodular lesion composed of small to medium sized oval or polygonal epithelioid cells and plump spindle shaped cells with eosinophilic cytoplasm and mildly atypical nuclei with vesicular chromatic and small nucleoli. The nodules contain centralized necrosis and hemorrhage imparting a granulomatous appearance to the process on low power magnification. The epithelioid cells are concentrated towards the center of the nodules with peripheral spindling. Aggregates of chronic inflammatory cells are present at the periphery of the nodules. The mitotic activity is low: 4 mitoses / 10 high power fields. The lesion involves the underlying facia. Immunohistochemically the epithelioid and spindled cells show strong expression of CAM5.2, EMA and CD34 and are negative for CD31 and CD68. There is loss of INI1 expression in lesional cells. This constellation of morphological and immunohistochemical features strongly supports the diagnosis of epithelioid sarcoma, classic type. The course of epithelioid sarcoma is often unpredictable and it is common for patients to present with extensive disease, lymph node metastases, or distant metastases.
Differential diagnosis
Board review style question #1
    Which of the following is true about epithelioid sarcoma?

  1. ~30% of cases metastasize
  2. Diagnosis always requires clinicopathological and radiological correlation
  3. Epithelioid sarcoma is positive for MDM2 amplification by FISH
  4. Pediatric patients appear to have a better prognosis
  5. Tumor is characterized by marked nuclear pleomorphism in most cases
Board review style answer #1
D. Pediatric patients appear to have a better prognosis

Comment Here

Reference: Epithelioid sarcoma
Board review style question #2

    A 53 year old man presents with a left hip mass. Hematoxylin-eosin stains demonstrate multinodular and sheet-like growth of large epithelioid cells with enlarged vesicular nuclei and prominent nucleoli. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and foci of tumor necrosis are frequently encountered. Mitotic figures are uncommon (5 mitoses / 10 high power fields). The lesion involves deep soft tissue and underlying bone. Immunohistochemical stains for EMA, CAM5.2 and CD34 are positive in epithelioid cells and there is loss of INI1 expression. Stains for SMA, myogenin, MyoD1, CD31, FLI1 and SALL4 are negative. Which of the following is most likely the correct diagnosis?

  1. Epithelioid angiosarcoma
  2. Epithelioid hemangioendothelioma
  3. Epithelioid sarcoma, proximal type
  4. Extrarenal rhabdoid tumor
  5. Pleomorphic rhabdomyosarcoma
Board review style answer #2
C. Epithelioid sarcoma, proximal type

Comment Here

Reference: Epithelioid sarcoma
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