Stanford School of Medicine

Surgical Pathology Criteria
http://surgpathcriteria.stanford.edu/

 use browser back button to return

Clear Cell Sarcoma

Definition

  • Primary soft tissue neoplasm exhibiting evidence of melanocytic differentiation

Alternate / historical names

  • Malignant melanoma of soft parts
  • Clear cell sarcoma of tendons and aponeuroses

Diagnostic criteria

  • Irregular nests of cells separated by fibrous septa
    • Cells may be in short fascicles, whorls or solid sheets
    • Necrosis frequent
    • Rarely with prominent lymphocytes along septa creating a seminoma-like pattern
    • Rarely with discohesion creating an alveolar pattern
  • Round to fusiform, non-pleomorphic cells
    • Pleomorphism rare except in recurrent disease
    • Regular vesicular nuclei
    • Prominent single nucleolus
    • Multinucleated tumor giant cells may be seen
    • Mitotic figures infrequent
      • Median 2/10 HPF, rarely up to 43/10 HPF
  • Moderate to abundant cytoplasm
    • Clear to granular eosinophilic
    • Glycogen frequently present
    • Rhabdoid cells may be seen in occasional cases
  • S100 and HMB45 positive in about 80% of cases
    • Melanin stain frequently positive

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

    Original posting: July 19, 2007
    Last Update: June 26, 2008

 

Supplemental studies

Immunohistology

  • Melanocytic markers positive, but some reports suggest less frequently than melanomas
    S100 70-100%
    HMB45 70-97%
    Mitf 70-80%
    MelanA 40-70%
    bcl2 93%
    EMA 36%
    CD117 0-15%
    CD34 0-9%
  • Keratin: Negative (one report of 30% positive)
  • Actin, desmin: Negative

Genetic analysis

  • t(12;22)(q13;q12) identified in 75-90% of cases tested
  • t(2;22)(q34;q12) identified in a minority of cases
    • Preferentially seen in cases arising in the lower GI tract
  • Both involve EWS gene involved in PNETs
  • These translocations not identified in melanomas but are found in angiomatoid fibrous histiocytomas

Differential Diagnosis

The first five entities are either melanocytic or HMB45 positive and thus may be confused with clear cell sarcoma

Melanoma Clear Cell Sarcoma
Evidence of skin primary Deep origin
Nuclear pleomorphism frequent Nuclear pleomorphism infrequent
Mitoses frequently numerous Mitoses usually infrequent
t(11;12) not present t(11;12) frequent
CD117 65% CD117 negative

 

Cellular Blue Nevus Clear Cell Sarcoma
Usually on trunk Usually on extremities
Usually superficial Involves tendons and deep fascia

 

Malignant Blue Nevus Clear Cell Sarcoma
Usually on scalp Usually on extremeties
Superficial Deep
Frequently associated with benign blue nevus No association with blue nevus

 

PEComa Clear Cell Sarcoma
S100 30% S100 80%
Actin 90% Actin negative

 

Paraganglioma-like Dermal Melanocytic Tumor Clear Cell Sarcoma
Based in dermis Deep soft tissue and tendons
Nucleoli not prominent Prominent large nucleoli
Lacks necrosis Frequent necrosis

 

Epithelioid Leiomyosarcoma Clear Cell Sarcoma
No irregular nests Usually irregular nests
HMB45 negative HMB45 80% positive
Actin, desmin positive Actin, desmin negative

 

Malignant Peripiheral Nerve Sheath Tumor Clear Cell Sarcoma
Associated with nerve, neurofibroma or von Recklinghausen disease No such association
Melanin and HMB45 rare Melanin and HMB45 80% positive
Frequently pleomorphic Pleomorphism infrequent
Mitoses usually frequent Mitoses usually infrequent

 

Synovial Sarcoma Clear Cell Sarcoma
Dense nuclei with stippled chromatin Vesicular nuclei with prominent nucleoli
Keratin 50-80% positive Keratin negative (one report of 30% positive)
Melanin and HMB45 negative Melanin and HMB45 positive 80%
Calcification common Calcification uncommon
SYT-SSX gene fusion present t(11;12) frequent
TLE1 97% TLE1 14%

 

Paraganglioma Clear Cell Sarcoma
Salt and pepper chromatin Vesicular chromatin with nucleoli
Chromogranin, synaptophysin positive HMB45 positive 80%, MelanA positive 40%
S100+ sustentacular cells No sustentacular cells

Clinical

  • Age range 5-80 years, predominantly 15-35 years
  • Location
    • Predominantly feet, ankles, knees
    • Most of remaining cases on upper extremity
    • Rarely involves head and neck
    • Usually involves tendon, aponeuroses or deep fascia
    • Rare cases reported from lower GI tract
  • Size >5 cm associated with metastases
  • Metastases
    • Frequently to lung or lymph nodes
    • May occur late, after 5 years
  • 50% 5 year survival

Grading / Staging / Report

According to the guidelines of the ADAP, clear cell sarcoma should not be graded because grade does not predict outcome

French Federation of Cancer Centers System grading scheme for adult sarcomas

  • Tumor differentiation score = 3 for clear cell 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
  • State that this sarcoma is not considered gradable by the ADAP
  • 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

HMB45 positive neoplasms/processes

  • Angiomyolipoma
  • Clear cell sarcoma
  • Clear cell (sugar) tumor of lung
  • Dysplastic nevi (variable staining)
  • Lymphangioleiomyomatosis
  • Melanoma
  • PEComas
  • Pigmented basal cell carcinoma
  • Pigmented nerve sheath tumor
  • Pigmented neuroepithelioma of infancy

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
  • Chung EB, Enzinger FM. Malignant melanoma of soft parts. A reassessment of clear cell sarcoma. Am J Surg Pathol 1983 Jul;7(5):405-13.
  • d'Amore ES, Ninfo V. Clear cell tumors of the somatic soft tissues. Semin Diagn Pathol 1997 Nov;14(4):270-80.
  • Deenik W, Mooi WJ, Rutgers EJ, Peterse JL, Hart AA, Kroon BB. Clear cell sarcoma (malignant melanoma) of soft parts: A clinicopathologic study of 30 cases. Cancer 1999 Sep 15;86(6):969-75.
  • Granter SR, Weilbaecher KN, Quigley C, Fletcher CD, Fisher DE. Clear cell sarcoma shows immunoreactivity for microphthalmia transcription factor: further evidence for melanocytic differentiation. Mod Pathol 2001 Jan;14(1):6-9.
  • Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM, Baelde JJ, Hogendoorn PC. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Cancer 2001 Feb;84(4):535-8.
  • Lucas DR, Nascimento AG, Sim FH. Clear cell sarcoma of soft tissues. Mayo Clinic experience with 35 cases Am J Surg Pathol 1992 Dec;16(12):1197-204.
  • Marques B, Terrier P, Voigt JJ, Mihura J, Coindre JM. [Clear cell soft tissue sarcoma. Clinical, histopathological and prognostic study of 36 cases] Ann Pathol 2000 Sep;20(4):298-303.
  • Mooi WJ, Deenik W, Peterse JL, Hogendoorn PC. Keratin immunoreactivity in melanoma of soft parts (clear cell sarcoma). Histopathology 1995 Jul;27(1):61-5.
  • Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: clear cell sarcoma (malignant melanoma of soft parts). Cancer Genet Cytogenet 2001 Oct 1;130(1):1-7.
  • Swanson PE, Wick MR. Clear cell sarcoma. An immunohistochemical analysis of six cases and comparison with other epithelioid neoplasms of soft tissue. Arch Pathol Lab Med 1989 Jan;113(1):55-60.
  • Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med. 2007 Jan;131(1):152-6.
  • Garcia JJ, Kramer MJ, Mackey ZB, O'Donnell RJ, Horvai AE. Utility of CD117 immunoreactivity in differentiating metastatic melanoma from clear cell sarcoma. Arch Pathol Lab Med. 2006 Mar;130(3):343-8.
  • Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006 Sep 15;12(18):5356-62.
  • Hisaoka M, Ishida T, Kuo TT, Matsuyama A, Imamura T, Nishida K, Kuroda H, Inayama Y, Oshiro H, Kobayashi H, Nakajima T, Fukuda T, Ae K, Hashimoto H. Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol. 2008 Mar;32(3):452-60.
  • Meis-Kindblom JM. Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity. Adv Anat Pathol. 2006 Nov;13(6):286-92.
  • Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med. 2007 Jan;131(1):152-6.
  • Kawai A, Hosono A, Nakayama R, Matsumine A, Matsumoto S, Ueda T, Tsuchiya H, Beppu Y, Morioka H, Yabe H; Japanese Musculoskeletal Oncology Group.  Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients. Cancer. 2007 Jan 1;109(1):109-16.
 
Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
© 2005  Stanford University School of Medicine