Stanford School of Medicine
Surgical Pathology Criteria
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Proximal Type Epithelioid Sarcoma


Alternate/Historical Names

  • Large cell epithelioid sarcoma

Diagnostic Criteria

  • 95% keratin positive
    • CD34 50%
  • Most often involves pelvis, perineum and proximal extremities
    • May involve head, neck and trunk
    • May involve penis and vulva
  • Median age 35-40 years
  • Poorly circumscribed, may be multinodular
    • Separate and fused nodules and sheets of cells
    • Granuloma-like nodularity less common than in classical type epithelioid sarcoma
  • Medium to large epithelioid and spindled cells often with rhabdoid appearance
    • Rarely predominantly spindled
    • Abundant brightly eosinophilic to amphophilic cytoplasm
    • Frequently with sharp cell borders
    • Often has eccentric nuclei
    • 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
  • Variant patterns
    • Fibroma-like
      • Pure spindled cells
    • Angiomatoid
      • Large vascular-like spaces formed by discohesion
      • May be blood filled
    • Large cell or rhabdoid
      • Largely coincides with proximal type
  • Other than the name, proximal type epithelioid sarcoma shares only the distinctive keratin positive, CD34 frequently positive phenotype of classical 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
Updates: January 21, 2009


Supplemental studies


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

Genetic study

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

Differential Diagnosis


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


Proximal Type Epithelioid Sarcoma Monophasic Synovial Sarcoma
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
Both may present as keratin positive spindle cell neoplasms


Epithelioid or rhabdoid cytoplasm may raise the following possibilities

Epithelioid Angiosarcoma Proximal Type Epithelioid Sarcoma
CD31 usually positive CD31 negative
May have adjacent atypical small channels No small atypical channels
  • CD34 and keratin may be positive in both.
  • Angiomatoid variant epithelioid sarcoma may be more difficult to distinguish as it may have large blood filled spaces.
  • Keratin positivity as well as cytoplasmic features may cause confusion between these two.

    Extrarenal Rhabdoid Tumor Proximal Type Epithelioid Sarcoma
    CD34 negative CD34 50% positive
    No intensely eosinophilic collagen Intensely eosinophilic collagen
    Median age 8-9 years Median age 35-40 years
    Wide range of sites Predilection for genitalia
    It is probable that malignant rhabdoid tumors do not occur in adults - most if not all are carcinoma, melanoma or proximal epithelioid sarcoma


    • Median age 35-40 years
    • Most often involves pelvis, perineum and proximal extremities
      • May involve head, neck and trunk
      • May involve penis and vulva
    • Recurrence rate 65-70%
    • Metastatic rate 45-75%


    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


    Keratin positive soft tissue tumors (frequent and strong)

    CD34 positive neoplasms (frequent and strong)


    • 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
    • Hasegawa T, Matsuno Y, Shimoda T, Umeda T, Yokoyama R, Hirohashi S. Proximal-type epithelioid sarcoma: a clinicopathologic study of 20 cases. Mod Pathol 2001 Jul;14(7):655-63
    • Debiec-Rychter M, Sciot R, Hagemeijer A. Common chromosome aberrations in the proximal type of epithelioid sarcoma. Cancer Genet Cytogenet 2000 Dec;123(2):133-6
    • 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
    • Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. "Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol 1997 Feb;21(2):130-46
    • 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.
    • 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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