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Surgical Pathology Criteria
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Epithelioid Sarcoma

Definition

Alternate/Historical Names

  • Classical type epithelioid sarcoma
  • Large cell epithelioid sarcoma

Diagnostic Criteria

  • 95% keratin positive
    • CD34 50%
  • Almost always involves distal extremities of young adults and children
  • Poorly circumscribed, often multinodular
    • Separate and fused nodules and sheets of cells
  • Frequent central necrosis
    • May appear histologically as necrotic granulomas
  • Brightly eosinophilic collagen in and around nodules
  • Medium to large epithelioid and spindled cells
    • Rarely predominantly spindled
    • Abundant brightly eosinophilic cytoplasm
    • Frequently with sharp cell borders
    • Nuclei may be eccentric
    • Moderate nuclear pleomorphism
    • Mitotic figures infrequent to numerous
  • Occasional features
    • Perineural invasion
    • Vascular invasion
    • Myxoid areas or extensive hyalinization
    • Calcification or ossification
    • Hemorrhage
    • Cyst formation
    • Small cell pattern with scant cytoplasm
  • Fibroma-like variant
    • Pure spindled cells
  • Other than the name, classical type epithelioid sarcoma shares only the distinctive immunophenotype of proximal type epithelioid sarcoma.

Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: July 27, 2007
Latest update: December 12, 2008

 

Supplemental studies

Immunohistology

  • CD34 50%
  • Keratin 95%
    • Low molecular weight keratin CK8 is positive in 95%
    • High molecular weight keratins rare to 50%
    • CK7 22% and CK20 0-15%
  • INI1 loss in 91%
EMA 95%
Vimentin >95%
CA125 90%
Actin (MSA or SMA) 30-40%
Desmin 15-70%
S100 Rare
CD31 Negative
Factor VIII Negative
  • Higher rate of desmin reactivity reported in proximal type disease

Genetic study

Loss of heterozygosity on chromosome 22 has been detected in some cases

Differential Diagnosis

Central necrosis of epithelioid sarcoma may simulate granulomatous disease, infectious or autoimmune
Palisaded Necrotic Granuloma Epithelioid Sarcoma
Keratin negative Keratin positive
CD34 negative CD34 50% positive
Indistinct cytoplasm Sharply defined eosinophilic cytoplasm
Rheumatoid nodules uncommon on hand and wrist Common on hand and wrist
Always think of epithelioid sarcoma when an extremity lesions looks granulomatous

 

Keratin positivity is typically seen in both
Squamous Carcinoma Epithelioid Sarcoma
CD34 negative CD34 50% positive
Uncommon in young people Most patients under 40 years
May have in situ lesion or keratinization No in situ lesion or keratinization
May have history of epithelial primary No primary epithelial lesion
CK5/6 commonly extensive CK5/6 rare, focal
CA125 negative in cutaneous SCC, frequently positive in SCC of other sites CA125 90% positive
CD34 reactivity is very rare in carcinoma of any type

 

Keratin positivity is typically seen in both
Sweat Gland Carcinoma Epithelioid Sarcoma
CD34 negative CD34 50% positive
May express GCDFP15, S100, actin GCDFP15, S100, actin negative
CD34 reactivity is very rare in carcinoma of any type

 

Both may present as keratin positive spindle cell neoplasms
Epithelioid Sarcoma Monophasic Synovial Sarcoma
Usually superficial Usually deep
Necrosis frequently extensive Necrosis usually focal
CD34 50% positive CD34 negative
No ropy collagen Ropy collagen frequent
Calcification infrequent Calcification frequent
No hemangiopericytomatous vessels Hemangiopericytomatous vessels frequent
No SYT-SSX gene fusion SYT-SST gene fusion present
TLE1 0% (0/2) TLE1 97%
CA125 90% positive CA125 negative

 

Abundant well defined cytoplasm in a dermal tumor may simulate melanoma
Melanoma Epithelioid Sarcoma
S100, HMB45 positive S100, HMB45 negative
Keratin very rare Keratin positive
CD34 negative CD34 50% positive
May have adjacent junctional component No junctional component
CA125 negative CA125 90% positive
INI1 positive INI1 loss in 91%

 

Epithelioid Hemangioendothelioma Epithelioid Sarcoma
CD31 usually positive CD31 negative
Keratin negative Keratin positive
Uncommon on distal extremities Common distally
Frequently small nested pattern Nodular or sheets
May be centered on a vessel Not centered on a vessel

 

Epithelioid Sarcoma Sclerosing Epithelioid Fibrosarcoma
EMA and keratin often strongly positive EMA and keratin negative or focal and weak
Often granuloma-like Cords of cells in hyalinized stroma
Eosinophilic cytoplasm Clear cytoplasm

 

Epithelioid Sarcoma Ischemic Fasciitis
Usually extremities of young patient Usually shoulder or hip of elderly patient
Usually brightly eosinophilic cytoplasm Cytoplasm usually basophilic or amphophilic
Keratin positive Keratin negative
Both are frequently CD34 positive

Clinical

  • Classical type
    • Age range 11-64 years but most in children and young adults
    • Most on distal extremities
      • Usually fingers, hand, wrist
    • Involves dermis, subcutaneous and deep soft tissue
    • May ulcerate
    • Under 1 cm to 15 cm
    • Recurrence rate 38-77%
    • Metastatic rate 45%
      • May metastasize to nodes

Grading / Staging / Report

According to the guidelines of the ADASP, epithelioid sarcoma is not graded but often metastasizes

French Federation of Cancer Centers System grading scheme for adult sarcomas

  • Tumor differentiation score = 3 for epithelioid sarcoma
  • Mitotic index
    • Score 1 0-9 mitoses per 10 hpf (0.1744 sq mm)
    • Score 2 10-19 mitoses per 10 hpf
    • Score 3 >19 mitoses per 10 hpf
  • Tumor cell necrosis
    • Score 0 No necrosis on any slide (one slide per 2 cm tumor diameter)
    • Score 1 <50% of tumor is necrotic on slides examined
    • Score 2 >50% of tumor is necrotic on slides examined
  • Final Grade (add the three scores above)
    • Grade 1 Sum of scores = 2 or 3
    • Grade 2 Sum of scores = 4 or 5
    • Grade 3 Sum of scores = 6 or more

Use TNM Staging

The surgical pathology report should contain or address the following:

  • Location
  • Type of resection or biopsy
  • Histologic diagnosis
  • Managerial category III (Local recurrence common, metastasis may occur)
  • Extent of tumor cell necrosis
  • Grade
  • Stage
  • Size
  • Depth (dermis, subcutis, below fascia, body cavity)
  • Margins
    • Involved
    • Not involved
      • If under 2 cm give all such distances and sites
      • If over 2 cm give minimum distance and site
  • Results of supplementary studies if performed
  • Relationship to other specimens from the same patient

Lists

Keratin positive soft tissue tumors (frequent and strong)

CD34 positive neoplasms (frequent and strong)

Bibliography

  • Kempson RL, Fletcher CDM, Evans HL, Henrickson MR, Sibley RS. Tumors of the Soft Tissues, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 30, 2001
  • Fletcher CDM, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone, World Health Organization Classification of Tumours 2002
  • Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors, 4th edition, 2001
  • Fisher C. Epithelioid sarcoma of Enzinger. Adv Anat Pathol. 2006 May;13(3):114-21
  • Miettinen M, Fanburg-Smith JC, Virolainen M, Shmookler BM, Fetsch JF. Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol 1999 Aug;30(8):934-42
  • Ishida T, Oka T, Matsushita H, Machinami R. Epithelioid sarcoma: an electron-microscopic, immunohistochemical and DNA flow cytometric analysis. Virchows Arch A Pathol Anat Histopathol 1992;421(5):401-8
  • Halling AC, Wollan PC, Pritchard DJ, Vlasak R, Nascimento AG. Epithelioid sarcoma: a clinicopathologic review of 55 cases. Mayo Clin Proc 1996 Jul;71(7):636-42
  • Chase DR, Enzinger FM. Epithelioid sarcoma. Diagnosis, prognostic indicators, and treatment. Am J Surg Pathol 1985 Apr;9(4):241-63
  • Evans HL, Baer SC. Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases. Semin Diagn Pathol 1993 Nov;10(4):286-91
  • el-Naggar AK, Garcia GM. Epithelioid sarcoma. Flow cytometric study of DNA content and regional DNA heterogeneity. Cancer 1992 Apr 1;69(7):1721-8
  • Feely MG, Fidler ME, Nelson M, Neff JR, Bridge JA. Cytogenetic findings in a case of epithelioid sarcoma and a review of the literature. Cancer Genet Cytogenet 2000 Jun;119(2):155-7
  • Quezado MM, Middleton LP, Bryant B, Lane K, Weiss SW, Merino MJ. Allelic loss on chromosome 22q in epithelioid sarcomas. Hum Pathol 1998 Jun;29(6):604-8
  • Laskin WB, Miettinen M. Epithelioid sarcoma: new insights based on an extended immunohistochemical analysis. Arch Pathol Lab Med. 2003 Sep;127(9):1161-8.
  • Humble SD, Prieto VG, Horenstein MG. Cytokeratin 7 and 20 expression in epithelioid sarcoma. J Cutan Pathol. 2003 Apr;30(4):242-6.
  • Lin L, Skacel M, Sigel JE, Bergfeld WF, Montgomery E, Fisher C, Goldblum JR. Epithelioid sarcoma: an immunohistochemical analysis evaluating the utility of cytokeratin 5/6 in distinguishing superficial epithelioid sarcoma from spindled squamous cell carcinoma. J Cutan Pathol. 2003 Feb;30(2):114-7.
  • Kato H, Hatori M, Kokubun S, Watanabe M, Smith RA, Hotta T, Ogose A, Morita T, Murakami T, Aiba S. CA125 expression in epithelioid sarcoma. Jpn J Clin Oncol. 2004 Mar;34(3):149-54.
  • Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 Expression is Characteristic of Both Conventional and Proximal-type Epithelioid Sarcoma. Am J Surg Pathol. 2009. [Epub ahead of print]

 

 
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