Head and Neck Pathology

, Volume 10, Issue 2, pp 161–166 | Cite as

Low-Grade Fibromyxoid Sarcoma of the Head and Neck: A Clinicopathologic Series and Review of the Literature

  • Morgan L. CowanEmail author
  • Lester D. Thompson
  • Marino E. Leon
  • Justin A. Bishop
Original Paper


Low-grade fibromyxoid sarcoma (LGFMS) is a deceptively bland malignancy with potential for late recurrence and metastasis, which usually occurs in the deep soft tissues of the extremities and trunk. Most LGFMSs harbor a characteristic gene fusion of FUS-CREB3L2, and recently MUC4 immunostaining has been found to be highly sensitive and specific for the diagnosis. We present a dedicated series of head and neck LGFMS, including the first reported laryngeal case, as well as a review of reported head and neck cases. The surgical pathology archives of our three institutions were searched for cases of LGFMS arising within the head and neck, and four cases were identified. The H&E slides were reviewed, and immunohistochemistry were performed for pancytokeratin, p63, p40, EMA, S100 protein, β-catenin, actin, CD34, and MUC4. The patients were 6, 43, 45, and 73 years old (mean 41.8 years) and included three males and one female. The tumors were located in the posterior cervical spine, facial skin, mandible, and larynx. The tumors were treated with surgical excision, and all four had histologic features typical for LGFMS including alternating myxoid and fibrous areas with prominent curvilinear vasculature. All tumors were MUC4 positive (100%), 2/4 (50%) were p63 positive, 1/4 (25%) showed focal EMA positivity; all 4 were negative for pancytokeratin, p40, S100 protein, β-catenin, actin, and CD34. LGFMS is a low grade sarcoma that rarely develops in the head and neck. Due to its rarity, a pathologist may not consider LGFMS in the differential diagnosis of spindle cell neoplasms within the head and neck. Immunohistochemical staining is helpful, but stains should be selected carefully to avoid misdiagnosis.


Low-grade fibromyxoid sarcoma MUC4 Head and neck sarcoma p63 p40 


  1. 1.
    Bentz BG, Singh B, Woodruff J, et al. Head and neck soft tissue sarcomas: a multivariate analysis of outcomes. Ann Surg Oncol. 2004;11:619–28.CrossRefPubMedGoogle Scholar
  2. 2.
    Barosa J, Ribeiro J, Afonso L, et al. Head and neck sarcoma: analysis of 29 cases. Eur Ann Otorhinolaryngol Head Neck Dis. 2014;131:83–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Peng KA, Grogan T, Wang MB. Head and neck sarcomas: analysis of the seer database. Otolaryngol Head Neck Surg. 2014;151:627–33.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Tajudeen BA, Fuller J, Lai C, et al. Head and neck sarcomas: the UCLA experience. Am J Otolaryngol—Head Neck Med Surg. 2014;35:476–81.Google Scholar
  5. 5.
    Tejani MA, Galloway TJ, Lango M, et al. Head and neck sarcomas: a comprehensive cancer center experience. Cancers (Basel). 2013;5:890–900.CrossRefGoogle Scholar
  6. 6.
    Evans HL. Low-grade fibromyxoid sarcoma. A report of two metastasizing neoplasms having a deceptively benign appearance. Am J Clin Pathol. 1987;88:615–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Folpe AL, Lane KL, Paull G, et al. 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;24:1353–60.CrossRefPubMedGoogle Scholar
  8. 8.
    Evans HL. Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol. 2011;35:1450–62.CrossRefPubMedGoogle Scholar
  9. 9.
    Evans HL. Low-grade fibromyxoid sarcoma. A report of 12 cases. Am J Surg Pathol. 1993;17:595–600.CrossRefPubMedGoogle Scholar
  10. 10.
    Guillou L, Benhattar J, Gengler C, et al. 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 Gro. Am J Surg Pathol. 2007;31:1387–402.CrossRefPubMedGoogle Scholar
  11. 11.
    Rekhi B, Deshmukh M, Jambhekar NA. Low-grade fibromyxoid sarcoma: a clinicopathologic study of 18 cases, including histopathologic relationship with sclerosing epithelioid fibrosarcoma in a subset of cases. Ann Diagn Pathol. 2011;15:303–11.CrossRefPubMedGoogle Scholar
  12. 12.
    Marglani O, Commons S, Lamothe A. Radiation-induced low-grade fibromyxoid sarcoma of the sternocleidomastoid muscle. J Otolaryngol. 2007;36:E73–5.PubMedGoogle Scholar
  13. 13.
    Papadimitriou JC, Ord RA, Drachenberg CB. Head and neck fibromyxoid sarcoma: clinicopathological correlation with emphasis on peculiar ultrastructural features related to collagen processing. Ultrastruct Pathol. 1997;21:81–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Tang Z, Zhou Z, Lv C, et al. Low-grade fibromyxoid sarcoma: clinical study and case report. J Oral Maxillofac Surg. 2010;68:873–84.CrossRefPubMedGoogle Scholar
  15. 15.
    Doyle LA, Möller E, Dal Cin P, et al. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2011;35:733–41.CrossRefPubMedGoogle Scholar
  16. 16.
    Panagopoulos I, Storlazzi CT, Fletcher CDM, et al. The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma. Genes Chromosomes Cancer. 2004;40:218–28.CrossRefPubMedGoogle Scholar
  17. 17.
    Park IJ, Kim HC, Yu CS, et al. Low-grade fibromyxoid sarcoma of the colon. Dig Liver Dis. 2007;39:274–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Jakowski JD, Wakely PE. Primary intrathoracic low-grade fibromyxoid sarcoma. Hum Pathol. 2008;39:623–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Lee AF, Yip S, Smith AC, et al. Low-grade fibromyxoid sarcoma of the perineum with heterotopic ossification: case report and review of the literature. Hum Pathol. 2011;42:1804–9.CrossRefPubMedGoogle Scholar
  20. 20.
    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;21:1481–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Reid R, de Silva MVC, Paterson L, et al. 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;27:1229–36.CrossRefPubMedGoogle Scholar
  22. 22.
    Zamenik M. Low-grade fibromyxoid sarcoma: a report of eight cases with histologic, immunohistochemical, and ultrastructural study. Ann Diagn Pathol. 2000;4:207–17.CrossRefGoogle Scholar
  23. 23.
    Doyle LA, Wang W-L, Dal Cin P, et al. MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma. Am J Surg Pathol. 2012;36:1444–51.CrossRefPubMedGoogle Scholar
  24. 24.
    Storlazzi CT, Mertens F, Nascimento A, et al. Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma. Hum Mol Genet. 2003;12:2349–58.CrossRefPubMedGoogle Scholar
  25. 25.
    Bartuma H, Möller E, Collin A, et al. Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome in low-grade fibromyxoid sarcoma. Cancer Genet Cytogenet. 2010;199:143–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Mezzelani A, Sozzi G, Nessling M, et al. Low grade fibromyxoid sarcoma. A further low-grade soft tissue malignancy characterized by a ring chromosome. Cancer Genet Cytogenet. 2000;122:144–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Lau PPL, Lui PCW, Lau GTC, et al. EWSR1-CREB3L1 gene fusion. Am J Surg Pathol. 2013;37:734–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Rubinstein JC, Visa A, Zhang L, et al. Primary low-grade fibromyxoid sarcoma of the kidney in a child with the alternative EWSR1-CREB3L1 gene fusion. Pediatr Dev Pathol. 2014;17:321–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Doyle LA, Wang W-L, Dal Cin P, et al. MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with FUS gene rearrangement. Am J Surg Pathol. 2012;36:1444–51.CrossRefPubMedGoogle Scholar
  30. 30.
    Prieto-Granada C, Zhang L, Chen H-W, et al. A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: a pathologic and molecular study of 18 cases. Genes Chromosomes Cancer. 2015;54:28–38.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Arbajian E, Puls F, Magnusson L, et al. Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. Am J Surg Pathol. 2014;00:1–8.Google Scholar
  32. 32.
    Hwang S, Kelliher E, Hameed M. Imaging features of low-grade fibromyxoid sarcoma (Evans tumor). Skelet Radiol. 2012;41:1263–72.CrossRefGoogle Scholar
  33. 33.
    Merchant SH. Low grade fibromyxoid sarcoma: report of a case with epithelioid cell morphology, masquerading as a papillary thyroid carcinoma. Acta Cytol. 2009;53:689–92.CrossRefPubMedGoogle Scholar
  34. 34.
    Viswanathan S, Rahman K, Pallavi S, et al. Sarcomatoid (spindle cell) carcinoma of the head and neck mucosal region: a clinicopathologic review of 103 cases from a tertiary referral cancer centre. Head Neck Pathol. 2010;4:265–75.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lewis JS, Ritter JH, El-Mofty S. Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1. Mod Pathol. 2005;18:1471–81.CrossRefPubMedGoogle Scholar
  36. 36.
    Thompson LDR, Wieneke JA, Miettinen M, et al. Spindle cell (sarcomatoid) carcinomas of the larynx: a clinicopathologic study of 187 cases. Am J Surg Pathol. 2002;26:153–70.CrossRefPubMedGoogle Scholar
  37. 37.
    Anderson CE, Al-Nafussi A. Spindle cell lesions of the head and neck: an overview and diagnostic approach. Diagn Histopathol. 2009;15:264–72.CrossRefGoogle Scholar
  38. 38.
    Olsen KD, Lewis JE, Suman VJ. Spindle cell carcinoma of the larynx and hypopharynx. Otolaryngol Head Neck Surg. 1997;116:47–52.CrossRefPubMedGoogle Scholar
  39. 39.
    Ansari-Lari MA, Hoque MO, Califano J, et al. Immunohistochemical p53 expression patterns in sarcomatoid carcinomas of the upper respiratory tract. Am J Surg Pathol. 2002;26:1024–31.CrossRefPubMedGoogle Scholar
  40. 40.
    Bishop JA, Montgomery EA, Westra WH. Use of p40 and p63 immunohistochemistry and human papillomavirus testing as ancillary tools for the recognition of head and neck sarcomatoid carcinoma and its distinction from benign and malignant mesenchymal processes. Am J Surg Pathol. 2014;38:257–64.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Miettinen M, Mccue PA, Sarlomo-rikala M, et al. Sox10—a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue. Am J Surg Pathol. 2015;39:1–10.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of PathologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Otolaryngology-Head and Neck SurgeryThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of PathologySouthern California Permanente Medical GroupWoodland HillsUSA
  4. 4.Department of Anatomic PathologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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