Abstract
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.
Similar content being viewed by others
References
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.
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.
Peng KA, Grogan T, Wang MB. Head and neck sarcomas: analysis of the seer database. Otolaryngol Head Neck Surg. 2014;151:627–33.
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.
Tejani MA, Galloway TJ, Lango M, et al. Head and neck sarcomas: a comprehensive cancer center experience. Cancers (Basel). 2013;5:890–900.
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.
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.
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.
Evans HL. Low-grade fibromyxoid sarcoma. A report of 12 cases. Am J Surg Pathol. 1993;17:595–600.
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.
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.
Marglani O, Commons S, Lamothe A. Radiation-induced low-grade fibromyxoid sarcoma of the sternocleidomastoid muscle. J Otolaryngol. 2007;36:E73–5.
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.
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.
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.
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.
Park IJ, Kim HC, Yu CS, et al. Low-grade fibromyxoid sarcoma of the colon. Dig Liver Dis. 2007;39:274–7.
Jakowski JD, Wakely PE. Primary intrathoracic low-grade fibromyxoid sarcoma. Hum Pathol. 2008;39:623–8.
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.
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.
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.
Zamenik M. Low-grade fibromyxoid sarcoma: a report of eight cases with histologic, immunohistochemical, and ultrastructural study. Ann Diagn Pathol. 2000;4:207–17.
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.
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.
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.
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.
Lau PPL, Lui PCW, Lau GTC, et al. EWSR1-CREB3L1 gene fusion. Am J Surg Pathol. 2013;37:734–8.
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.
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.
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.
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.
Hwang S, Kelliher E, Hameed M. Imaging features of low-grade fibromyxoid sarcoma (Evans tumor). Skelet Radiol. 2012;41:1263–72.
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.
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.
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.
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.
Anderson CE, Al-Nafussi A. Spindle cell lesions of the head and neck: an overview and diagnostic approach. Diagn Histopathol. 2009;15:264–72.
Olsen KD, Lewis JE, Suman VJ. Spindle cell carcinoma of the larynx and hypopharynx. Otolaryngol Head Neck Surg. 1997;116:47–52.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cowan, M.L., Thompson, L.D., Leon, M.E. et al. Low-Grade Fibromyxoid Sarcoma of the Head and Neck: A Clinicopathologic Series and Review of the Literature. Head and Neck Pathol 10, 161–166 (2016). https://doi.org/10.1007/s12105-015-0647-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12105-015-0647-8