Stanford School of Medicine
Surgical Pathology Criteria
use browser back button to return

Low Grade Fibromyxoid Sarcoma

Definition

  • Cytologically bland malignant neoplasm with alternating fibrous and myxoid stroma of low grade / low malignant potential

Alternate / Historical Names

  • Evans tumor
  • Hyalinizing spindle cell tumor with giant rosettes
  • Low grade fibrosarcoma with palisaded granuloma like bodies

Diagnostic Criteria

  • Grossly circumscribed, microscopically infiltrating
  • Alternating fibrous and myxoid stroma
    • Swirling, whorled pattern
    • Giant collagen rosettes in some cases
      • May simulate palisaded granulomas
      • Originally reported as hyalinizing spindle cell tumor with giant rosettes
      • Metastasis not observed in original report but subsequently has been reported
      • Appears to be in the spectrum of low grade fibromyxoid sarcoma
        • Smaller rosettes may be seen in typical low grade fibromyxoid sarcoma
        • Rosettes have been seen in metastases of a typical low grade fibromyxoid sarcoma
      • Clinicopathologic features otherwise appear identical
  • Generally hypocellular with bland spindle or stellate cells
    • Dark oval nuclei
      • Intranuclear inclusions may be seen
    • Pleomorphism absent or slight
    • Low to moderate cellularity
    • Scant cytoplasm
    • Mitotic figures rare
    • One reported case with abundant hemosiderin and synovial like clefts
  • MUC4 positive (see Supplemental Studies)
  • Focally occasional cases may deviate from above in primaries, recurrences or metastases
    • Focal hypercellular areas with epithelioid cells
    • May have herringbone pattern
    • Focally moderately hyperchromatic or pleomorphic
    • Focal necrosis
    • Increased capillary vascularity with curvilinear vessels
    • Focally mitotic figures >1/10 hpf
    • No clinical significance in two year followup
  • Based on a shared translocation and cases with mixed features sclerosing epithelioid fibrosarcoma has been proposed to form a spectrum with low grade fibromyxosarcoma

    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 100% strong diffuse positive (Doyle 2011)
Vimentin positive
Smooth muscle actin occasional focal weak positive
Desmin occasional focal weak positive
Keratin occasional focal weak positive
S100 occasional focal weak positive, may be positive in cells surrounding rosettes
CD34 occasional focal weak positive
EMA occasional focal weak positive
MUC4 also stains 78% of sclerosing epithelioid fibrosarcoma

Genetic analysis

  • Translocations involving fus t(7;16) seen in >90% and rarely t(11;16)

 

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)

Extra-abdominal Desmoid Fibromatosis Low Grade Fibromyxoid Sarcoma
Nuclei may be vesicular Small dark nuclei
Sweeping bundles of cells Swirling, whorled pattern
No rosettes May have collagenous rosettes
Frequent slit-like vessels No slit-like vessels

 

Myxofibrosarcoma Low Grade Fibromyxoid Sarcoma
Pleomorphic nuclei present At most, focal moderate pleomorphism, but usually minimal or absent
May be cellular Overall paucicellular
May have increased mitotic activity Few mitotic figures
Abnormal mitotic fibures may be present No abnormal mitotic figures
Lacks alternating fibrous and myxoid areas Features alternating fibrous and myxoid areas
Often subcutaneous Usually deep soft tissues

 

Aggressive Angiomyxoma Low Grade Fibromyxoid Sarcoma
Unifiorm myxoid pattern Alternating fibrous and myxoid patterns
Prominent large vessels No prominent large vessels
Restricted to pelvis, perineum, genitalia Frequently occurs in other sites
Desmin positive Usually desmin negative

 

Low Grade Fibromyxoid Sarcoma Intramuscular Myxoma
Alternating fibrous and myxoid patterns Uniform myxoid pattern
Swirling, whorled pattern No swirling, whorled pattern

 

Low Grade Fibromyxoid Sarcoma Juxta-articular Myxoma
Alternating fibrous and myxoid patterns Uniform myxoid pattern
Swirling, whorled pattern No swirling, whorled pattern

 

Low Grade Fibromyxoid Sarcoma Cellular Myxoma
Alternating fibrous and myxoid patterns Uniform myxoid pattern
Swirling, whorled pattern No swirling, whorled pattern

 

Neurofibroma Low Grade Fibromyxoid Sarcoma
May have thick collagen bundles Lacks thick collagen bundles
S100 positive S100 rare to negative, except may be positive around rosettes
No rosettes May have collagenous rosettes

 

Spindle Cell Atypical Lipomatous Tumor Low Grade Fibromyxoid Sarcoma
Adult fat integral to lesion No fat component
Lipoblasts may be present No lipoblasts
Abnormal mitotic fibures may be present No abnormal mitotic figures
Areas may be histologically identical

 

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

 

Soft Tissue Perineurioma Low Grade Fibromyxoid Sarcoma
Fibrous capsule Grossly circumscribed but microscopically infiltrating
Alternating pattern not prominent Alternating fibrous and myxoid stroma
Myxoid areas infrequent Myxoid areas definitional
EMA 100% positive EMA occasional focal weak positive

 

Myxoid DFSP Low Grade Fibromyxoid Sarcoma
Superficial Usually deep soft tissues
CD34 positive, nearly all cases Only occasional weak positivity
Usually more cellular Generally hypocellular, at most focally hypercellular

 

Nodular Fasciitis Low Grade Fibromyxoid Sarcoma
Usually superficial Usually deep soft tissues
S and C shaped bundleslll of cells Alternating fibrous and myxoid areas with whorling
Small Usually large
Essentially never metastasizes Metastatic rate reported from 6-60%, probably closer to 10%
LGFS may contain areas indistinguishable from nodular fasciitis; both are composed of bland cells

Clinical

  • Age 3-78 years, median age in 30’s
  • 1-23 cm
  • Predominantly trunk and lower extremities
    • Rare cases in mesentery and retroperitoneum
  • Most in deep soft tissue
    • About 10% in some series in subcutaneous tissue
  • Recurrence rate 10-75%
    • May take up to 15 years to recur
  • Metastatic rate 6-60%
    • Higher numbers may represent cases not treated initially as sarcomas
  • Rare cases reported with dedifferentiation after multiple recurrences
    • Anaplasia, increased cellularity, increased mitotic rate
    • Short survival after dedifferentiation

Report

  • Low grade fibromyxoid sarcoma is not considered gradable but may metastasize
  • French Federation of Cancer Centers System grading scheme for adult sarcomas
    • Tumor differentiation score = not defined for low grade fibromyxoid sarcoma

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
    • 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, 5th edition, 2008
  • Folpe AL, Lane KL, Paull G, Weiss SW. Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas. Am J Surg Pathol. 2000 Oct;24(10):1353-60.
  • Billings SD, Giblen G, Fanburg-Smith JC. Superficial low-grade fibromyxoid sarcoma (Evans tumor): a clinicopathologic analysis of 19 cases with a unique observation in the pediatric population. Am J Surg Pathol. 2005 Feb;29(2):204-10.
  • Reid R, de Silva MV, Paterson L, Ryan E, Fisher C. Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation. Am J Surg Pathol. 2003 Sep;27(9):1229-36.
  • Lane KL, Shannon RJ, Weiss SW. Hyalinizing spindle cell tumor with giant rosettes: a distinctive tumor closely resembling low-grade fibromyxoid sarcoma. Am J Surg Pathol. 1997 Dec;21:1481-8.
  • Guillou L, Benhattar J, Gengler C, Gallagher G, Ranchere-Vince D, Collin F, Terrier P, Terrier-Lacombe MJ, Leroux A, Marques B, de Saint Aubain Somerhausen N, 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.
  • Evans HL. Low-grade fibromyxoid sarcoma. A report of 12 cases. Am J Surg Pathol. 1993 Jun;17(6):595-600.
  • Scolyer RA, McCarthy SW, Wills EJ, Palmer AA. Hyalinising spindle cell tumour with giant rosettes: report of a case with unusual features including original histological and ultrastructural observations. Pathology. 2001 Feb;33(1):101-7.
  • Mezzelani A, Sozzi G, Nessling M, Riva C, Della Torre G, Testi MA, Azzarelli A, Pierotti MA, Lichter P, Pilotti S. Low grade fibromyxoid sarcoma. a further low-grade soft tissue malignancy characterized by a ring chromosome. Cancer Genet Cytogenet. 2000 Oct 15;122(2):144-8.
  • Zamecnik M, Michal M. Low-grade fibromyxoid sarcoma: a report of eight cases with histologic, immunohistochemical, and ultrastructural study. Ann Diagn Pathol. 2000 Aug;4(4):207-17.
  • Woodruff JM, Antonescu CR, Erlandson RA, Boland PJ. Low-grade fibrosarcoma with palisaded granulomalike bodies (giant rosettes): report of a case that metastasized. Am J Surg Pathol. 1999 Nov;23(11):1423-8.
  • Aoki T, Hisaoka M, Kouho H, Hashimoto H, Nakata H. Interphase cytogenetic analysis of myxoid soft tissue tumors by fluorescence in situ hybridization and DNA flow cytometry using paraffin-embedded tissue. Cancer. 1997 Jan 15;79(2):284-93.
  • Goodlad JR, Mentzel T, Fletcher CD. Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity. Histopathology. 1995 Mar;26(3):229-37.
  • Mertens F, Fletcher CD, Antonescu CR, Coindre JM, Colecchia M, Domanski HA, Downs-Kelly E, Fisher C, Goldblum JR, Guillou L, Reid R, Rosai J, Sciot R, Mandahl N, Panagopoulos I. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Invest. 2005 Mar;85(3):408-15.
  • 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.
  • Evans HL. Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol. 2011 Oct;35(10):1450-62.
  • 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.
 
Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
© 2005  Stanford University School of Medicine