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epithelioid sarcoma

Thursday 22 April 2004

Epithelioid sarcoma of soft tissue


Definition: Epithelioid sarcoma is a rare, malignant soft-tissue neoplasm occurring on the distal extremities of young adults.


- EPITHELIOID SARCOMA. NB: sheets of epithelioid cells w/ occasional ’rhabdoid’ features; small nucleoli; and, INI-1 deficient.

Digital cases

- HPC:176 : Epithelioid sarcoma of the hand.
- JRC:12138 : Epithelioid sarcoma of soft tissues.
- JRC:12142 : Epithelioid sarcoma of soft tissues.
- JRC:1795 : Epithelioid sarcoma of soft tissues.
- JRC:19139 : Epithelioid sarcoma of soft tissues.

First described in 1970, epithelioid sarcoma accounts for less than 1% of soft tissue sarcomas. It arises from multipotential mesenchymal cells able to express both epithelial and mesenchymal immunophenotype, and typically shows a slow-growing pattern.

Epithelioid sarcoma occurs more frequently in the upper limbs, usually involving the extremities (hand and wrist) of young to middle-aged male adults.

This "classic" form of epithelioid sarcoma is composed by cells varying from spindle to round and epithelioid, with necrotic areas.

A recently reported "proximal"-type variant is characterized by higher aggressiveness and preferential location in proximal-axial and deep regions.

Molecular biology


In a recent study, frequent deletions of INI1 gene have been detected in the proximal-type variant, by both real-time quantitative PCR analysis and immunohistochemistry.

Interestingly, the recognition of INI1 deletion in this extradural clival tumor with rhabdoid features reminds one of the atypical teratoid/rhabdoid tumor (AT/RT), a high malignant pediatric brain neoplasm, typically containing rhabdoid cells and divergent differentiation along epithelial, mesenchymal, neuronal or glial pathways.

AT/RTs are associated with inactivation of INI1 gene. Moreover, very similar morphological and immunohistochemical findings (including INI1 deletion) have been reported in both malignant renal and extra-renal rhabdoid tumors, thus making the differential diagnosis difficult and problematic.


Despite their slow growth, epithelioid sarcomas tend to spread locally, infiltrating regional lymph nodes and can present as multinodular and/or metastatic disease. The reported recurrence rate is as high as 70%.

Treatment is primarily by wide local excision, followed by adjuvant radiotherapy; however, even in cases of primary amputation of an affected limb, no survival advantage has been observed.

The final diagnosis required histologic examination which showed epithelioid neoplastic cells, with rounded nuclei and abundant eosinophilic cytoplasm, numerous mitoses, a high proliferative index and areas of necrosis. Immunohistochemistry, demonstrating a positive stain for vimentin, cytokeratins, and EMA, and the failure of BAF-47 antibody to stain neoplastic nuclei (suggesting INI1 deletion), were in favor of epithelioid sarcoma.


- proliferation of rounded to plump, spindle-shaped cells with abundant eosinophilic cytoplasm around areas of necrosis


- distal-type epithelioid sarcoma
- proximal-type epithelioid sarcoma (15078349)

  • pelvic and perineal areas
  • young to middle-aged adults
  • proliferation of epithelioid-like cells with rhabdoid features in the absence of a granuloma-like pattern
  • immunohistochemistry: vimentin+, cytokeratin+, epithelial membrane antigen+, CD34+
  • differential diagnosis: tumors with rhabdoid features, extrarenal malignant rhabdoid tumor


- proximal-type epithelioid sarcoma
- classic epithelioid sarcoma


- CK+ CKAE1/AE3+
- CD34+
- SMARCB1- (INI1-)
- ERG+ 60% (23774169)
- FLI1+ 70%
- CA125+

Differential diagnosis

- granulomatous inflammation
- epithelioid granulomas (tuberculoid granulomas)
- hemangioendotheliomas (12502927)


- bone: osseous epithelioid sarcoma (primary epithelioid sarcoma of bone) (19342946)
- parotid gland (19335024)

Molecular biology

- INI1 (SMARCB1) deletion (19342946)

Case studies

- UPMC #594


- ERG Expression in Epithelioid Sarcoma: A Diagnostic Pitfall. Miettinen M, Wang Z, Sarlomo-Rikala M, Abdullaev Z, Pack SD, Fetsch JF. Am J Surg Pathol. 2013 Jun 14. PMID: 23774169

- Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Hornick JL, Dal Cin P, Fletcher CD. Am J Surg Pathol. 2009 Apr;33(4):542-50. PMID: 19033866

- Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French sarcoma group. Chbani L, Guillou L, Terrier P, Decouvelaere AV, Grégoire F, Terrier-Lacombe MJ, Ranchère D, Robin YM, Collin F, Fréneaux P, Coindre JM. Am J Clin Pathol. 2009 Feb;131(2):222-7. PMID: 19141382 [Free]

- Primary Epithelioid Sarcoma of Bone: Report of a Unique Case, With Immunohistochemical and Fluorescent In Situ Hybridization Confirmation of INI1 Deletion. Raoux D, Péocʼh M, Pedeutour F, Vaunois B, Decouvelaere AV, Folpe AL. Am J Surg Pathol. 2009 Apr 1. PMID: 19342946

- INI1 and GLUT-1 expression in epithelioid sarcoma and its cutaneous neoplastic and nonneoplastic mimics. Orrock JM, Abbott JJ, Gibson LE, Folpe AL. Am J Dermatopathol. 2009 Apr;31(2):152-6. PMID: 19318800

- Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Kohashi K, Izumi T, Oda Y, Yamamoto H, Tamiya S, Taguchi T, Iwamoto Y, Hasegawa T, Tsuneyoshi M. Hum Pathol. 2009 Mar;40(3):349-55. PMID: 18973917

- "Proximal-type" and classic epithelioid sarcomas represent a clinicopathologic continuum: case report. Rakheja D, Wilson KS, Meehan J, Schultz RA, Gomez AM. Pediatr Dev Pathol. 2005 Jan-Feb;8(1):105-14. PMID: 15803217

- Epithelioid sarcoma: diagnosis, prognostic indicators, and treatment. Chase DR, Enzinger FM (1985) Am J Surg Pathol 9:241-261.

- Enzinger FM (1970) Epithelioid sarcoma: a sarcoma simulating a granuloma or a carcinoma. Cancer 26:1029-1041.

- Erdem E, Angtuaco EC, Van Hemert R, Park JS, Al-Mefty O (2003) Comprehensive review of intracranial chordoma. Radiographics 23:995-1009.

- Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD (1997) "Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol 21:130-46.

- Halling AC, Wollan PC, Pritchard DJ, Vlasak R, Nascimento AG (1996) Epithelioid sarcoma: a clinicopathologic review of 55 cases. Mayo Clin Proc 7:636-42.

- Hoot AC, Russo P, Judkins AR, Perlman EJ, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissues tumors. Am J Surg Pathol 28: 1485-1491.

- Kurtkaya-Yapícíer O, Scheithauer BW, Dedrick DJ, Wascher TM (2002) Primary epithelioid sarcoma of the dura: case report. Neurosurgery 50:198-202.

- Meyers SP, Hirsch WL Jr, Curtin HD, Barnes R, Sekhar LN, Sen C (1992) Chordomas of the skull base: MR features. Am J Neuroradiol 13:1627-1636.

- Modena P, Lualdi E, Facchinetti F, Galli L, Teixeira MR, Pilotti S, Sozzi G (2005) SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 65: 4012-4019.

- Pamir MN, Ozduman K (2006) Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas. Eur J Radiol 58:461-470.

- Spillane AJ, Thomas JM, Fisher C (2000) Epithelioid sarcoma: the clinicopathological complexities of this rare soft tissue sarcoma. Ann Surg Oncol 7: 218-225.

- Tsai EC, Santoreneos S, Rutka JT (2002) Tumors of the skull base in children: review of tumor types and management strategies. Neurosurg Focus 15; 12(5):e1.