Epithelioid sarcoma

Last revised by Joachim Feger on 22 Oct 2022

Epithelioid sarcomas are malignant usually slow-growing mesenchymal tumors of unknown and multidirectional differentiation. There are classic and proximal subtypes.

Epithelioid sarcomas are rare and make up for <1% of soft tissue sarcomas 1,2. They are found in children and adults over a wide age range with the classic subtype featuring a peak incidence in adolescence and young adults and the proximal subtype showing its peak later 1. There is a male predilection. The classic subtype is apparently almost twice as common as the proximal subtype 1.

Epithelioid sarcomas are diagnosed based on typical histological and molecular pathological features 1.

Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 1:

  • soft tissue mass (distal or proximal presentation)
  • epithelioid to spindled cell morphology
  • infiltrative growth
  • SMARCB1/INI1 loss
  • immunoreactivity for epithelial membrane antigen (EMA) and keratin

Epithelioid sarcomas usually present as single or multiple firm slow-growing mostly painless nodules, which can be associated with ulcers especially if located superficially. The proximal type is usually larger on detection 1.

Epithelioid sarcomas show a multidirectional differentiation similar to carcinomas and feature large polygonal cells or an epithelioid to spindled cytomorphology with an infiltrative growth pattern 1.

The etiology of epithelioid sarcomas is unknown. Some studies have been reporting a previous trauma which at this point is considered a probable coincidence 1.

The classic or conventional subtype is usually found in the distal extremities mostly affecting the volar surfaces of the hand and fingers with proximal extremities and trunk being less common sites of occurrence 1.

The large cell or proximal type, on the other hand, is more frequently found in deep soft tissues of the pelvic girdle, the perineal genital and inguinal regions, as well as buttock and hip and can, extend along tendon sheaths and/or fasciae 1.

There are two accepted subtypes of epithelioid sarcomas 1:

  • proximal or large cell epithelioid sarcoma
  • distal or classic epithelioid sarcoma

Macroscopically classic epithelioid sarcomas can present as small dermal or subcutaneous nodules or multinodular lesions extending along with fasciae and nerves. They can show yellowish to brown foci due to hemorrhage and necrosis and usually feature an otherwise shimmering grey-tannish to whitish appearance. The proximal subtype is usually larger on detection 1,2.

Histological features of epithelioid sarcomas include epithelioid cells and an infiltrative and nodular or multinodular growth pattern and differ slightly with respect to the subtype 1,2:

  • classical distal subtype
    • granulomatous appearance
    • might show spindled tumor cells
    • frequently skip lesions
    • aggregates of chronic inflammatory cells
    • dystrophic calcifications and metaplastic bone formation in about 1/5 of cases
  • large cell or proximal subtype
    • multinodular or sheet-like growth of epithelioid cells
    • enlarged vesicular nuclei and prominent nucleoli
    • rhabdoid features

Some epithelioid sarcomas have mixed or hybrid features of both subtypes 1.

Immunohistochemistry stains of both subtypes are usually positive for epithelial membrane antigen (EMA), vimentin and cytokeratins including CK8 and CK19 but are often negative for CK5/6. More than half of the cases show positivity of CD34 and predominantly the classic subtype shows reactivity to ERG in a fair number of cases 1,2.

Epithelioid sarcomas are associated with mutations of the SMARCB1 or INI1 gene resulting in a loss of SMARCB1 nuclear protein expression 1.

Epithelioid sarcomas have been characterized by a nodular or multinodular form and variable sometimes well-defined or irregular to ill-defined tumor margins 3,4.

On ultrasound, a temporally located case of epithelioid sarcoma has been described as a lobulated ill-defined hypoechoic lesion with a moderate extent of internal vascularity on color Doppler 5.

Epithelioid sarcomas have been described to show lobulated or multilobulated contours and some of the tumors have been described to show peripheral calcifications 3.

MR imaging features of epithelioid sarcomas are non-specific and feature inhomogeneous variable patterns due to variable amounts of necrosis, hemorrhage and granulomatous areas 3-6. Multiple soft tissue nodules possibly associated with ulcers should raise suspicion of this entity 4.

  • T1: variable
  • T2: inhomogeneous variably isointense to hyperintense compared to muscle
  • T1C+ (Gd): variable inhomogeneous and heterogeneous enhancement

Epithelioid sarcomas have been reported to show increased uptake of FDG 5,6.

The radiological report should include a description of the following:

  • form, location and size
  • tumor margins and transition zone
  • relations to the muscular fascia
  • relation to adjacent neurovascular structures
  • relations to bones

Multimodal management even of localized epithelioid sarcoma seems to have advantages in local tumor control. Local recurrence is seen in up to one-fourth of nodal involvement in one-third to half and metastatic disease in about one-third of the patients.

Overall survival rates have been reported to be in the range of 45-70% and 45-66% for 5 and 10 years respectively. Metastatic disease, nodal involvement, deep-seated tumors or proximal type, high mitotic activity, greater tumor size as well as older age of the patient are associated with a worse prognosis 1.

The tumor was first described by the Polish pathologist Jozef  Janusz Laskowski as aponeurotic sarcoma in 1961 in the journal Nowotwory 2 and later also by the American pathologists, Bryce O. Bliss and Richard J. Reed as large cell sarcomas of tendon sheath in 1968 2,8. Eventually, the name epithelioid sarcoma was introduced by the Austrian-American pathologist Franz Michael Enzinger in 1970, who characterized them as a distinct entity 2,5-7.

Tumors or conditions which can mimic the presentation and/or appearance of epithelioid sarcomas include 2:

ADVERTISEMENT: Supporters see fewer/no ads