Stanford School of Medicine
Surgical Pathology Criteria
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Sclerosing Epithelioid Fibrosarcoma

Definition

  • A rare malignant neoplasm composed of small round cells in nests and cords set in a hyalinized stroma

Diagnostic Criteria

  • Nests and cords of uniform epithelioid cells
    • Small to medium size
    • Round, oval or angulated nuclei
    • Scant clear to pale cytoplasm
  • Hyalinized stroma
    • May resemble osteoid
    • Cartilaginous and osseous metaplasia may be seen
    • May show focal myxoid change or calcification
  • MUC4 positive (see Supplemental Studies)
  • Variable cellularity
    • May produce nodular or lobular pattern
  • May have hemangiopericytomatous vessels
  • May have vascular invasion
  • Above pattern may merge with conventional fibrosarcoma pattern or with low grade fibromyxoid sarcoma pattern
  • Based on some cases with mixed features and on cases that share the t(7;16) (q32-34;p11) characteristic of low grade fibromyxoid sarcoma, it has been suggested that these two neoplasms may represent ends of a common spectrum
  • See separate entities:

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

    Original posting/last update: 10/15/07, 1/22/14

Supplemental studies

Immunohistology

MUC4 78% strong diffuse positive (Doyle 2012)
Vimentin positive
bcl2 90%
EMA 7/14 focal weak positive
S100 4/14 focal weak positive
Keratin 2/14 focal weak positive
NSE 2/14
Smooth muscle actin negative
Desmin negative
HMB45 negative
CD45RB (LCA) negative
CD68 negative
MUC4 also stains 100% of low grade fibromyxoid sarcoma

Genetic analysis

  • Translocations involving fus t(7;16) and rarely t(11;16) seen in 38% of MUC4 positive cases

Differential diagnosis

MUC4 reactivity (strong, diffuse) appears to be sensitive and specific for low grade fibromyxoid sarcoma (100%) and the related sclerosing epithelioid fibrosarcoma (78%) with reactivity in mesenchymal lesions seen othewise only in synovial sarcomas (weak focal reactions may be seen in other lesions) (Doyle 2011, 2012)

Low Grade Fibromyxoid Sarcoma Sclerosing Epithelioid Fibrosarcoma
Alternating fibrous and myxoid areas Generally myxoid stroma
Spindled or stellate cells Round, oval or angulated cells
EMA occasionally weak or focal EMA positive in 50% of cases
Quite different in appearance but based on cases with shared t(7;16) and cases with shared histologic features it has been suggested that these represent ends of a common spectrum

 

Carcinoma Sclerosing Epithelioid Fibrosarcoma
Usually widespread strong keratin staining Infrequent keratin staining, usually focal and weak
History of carcinoma primary No known primary
EMA may be positive in sclerosing epithelioid fibrosarcoma

 

Mesenchymal Chondrosarcoma Sclerosing Epithelioid Fibrosarcoma
Myxoid stroma Sclerotic, hyalinized stroma
Eosinophilic cytoplasm stretched between cells Cytoplasm usually clear, not stretched between cells
Both may grow in lobules with cords of cells

 

Adult Fibrosarcoma Sclerosing Epithelioid Fibrosarcoma
Spindled cells Round, oval or angulated cells
Scant stroma Prominent hyalinized stroma
EMA negative EMA focal weak positive in 50%
Sheets of cells Cords and nests of cells
Some tumors have areas of both patterns

 

Monoophasic Synovial Sarcoma Sclerosing Epithelioid Fibrosarcoma
Ropy collagen often surrounding cellular nests of sarcoma Hyalinized background
Sheets and nests of cells Cords and nests of cells
Keratin 50-80% positive Keratin rare, focal and weak
t(X;18) essentially all cases No t(X;18)
Both may be EMA positive

 

Ossifying Fibromyxoid Tumor Sclerosing Epithelioid Fibrosarcoma
EMA negative EMA 50% positive
Peripheral rim of bone in most cases Focal metaplastic bone at most

 

Osteosarcoma Sclerosing Epithelioid Fibrosarcoma
EMA negative May be EMA positive
Osteoid formed by malignant cells Sclerotic, hyalinized stroma; bone formation if present is metaplastic

 

Clear Cell Sarcoma Sclerosing Epithelioid Fibrosarcoma
S100 and HMB45 70-90% positive EMA 50% positive, HMB45 negative
Fibrous septa around nests of cells Cords and nests of cells in prominently sclerotic and hyalinized stroma
Both may have clear cytoplasm

 

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

Clinical

  • Age 14-87 years
  • Size 2-22 cm
  • Most reported cases on limbs, trunk, neck
    • Also reported in cord and brain, mesentery, omentum
  • Metastases reported in 43-86%
  • Bone invasion in 6/16 cases in one report
  • Note: very few cases have been reported

Report

  • French Federation of Cancer Centers System grading scheme for adult sarcomas
    • Tumor differentiation score = 2 for fibrosarcoma (no score provided for sclerosing epithelioid fibrosarcoma
    • 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 occurs)
    • 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

Predominantly fibrous soft tissue sarcomas

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
  • Guillou L, Benhattar J, Gengler C, Gallagher G, Ranchere-Vince D, Collin F, Terrier P, Terrier-Lacombe MJ, Leroux A, Marques B, Aubain Somerhausen Nde S, Keslair F, Pedeutour F, Coindre JM.  Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting  potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol. 2007 Sep;31(9):1387-402.
  • Antonescu CR, Rosenblum MK, Pereira P, Nascimento AG, Woodruff JM. Sclerosing epithelioid fibrosarcoma: a study of 16 cases and confirmation of a clinicopathologically distinct tumor. Am J Surg Pathol. 2001 Jun;25(6):699-709.
  • Bilsky MH, Schefler AC, Sandberg DI, Dunkel IJ, Rosenblum MK. Sclerosing epithelioid fibrosarcomas involving the neuraxis: report of three cases. Neurosurgery. 2000 Oct;47(4):956-9; discussion 959-60.
  • Donner LR, Clawson K, Dobin SM. Sclerosing epithelioid fibrosarcoma: a cytogenetic, immunohistochemical, and ultrastructural study of an unusual histological variant. Cancer Genet Cytogenet. 2000 Jun;119(2):127-31.
  • Eyden BP, Manson C, Banerjee SS, Roberts IS, Harris M. Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria. Histopathology. 1998 Oct;33(4):354-60.
  • Reid R, Barrett A, Hamblen DL. Sclerosing epithelioid fibrosarcoma. Histopathology. 1996 May;28(5):451-5.
  • Meis-Kindblom JM, Kindblom LG, Enzinger FM. Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol. 1995 Sep;19(9):979-93.
  • Doyle LA, Möller E, Dal Cin P, Fletcher CD, Mertens F, Hornick JL. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2011 May;35(5):733-41.
  • Doyle LA, Wang WL, Dal Cin P, Lopez-Terrada D, Mertens F, Lazar AJ, Fletcher CD, Hornick JL. MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with FUS gene rearrangement. Am J Surg Pathol. 2012 Oct;36(10):1444-51.

 

 
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