Low-grade fibromyxoid sarcoma: a clinicopathologic and molecular study of 10 genetically confirmed cases

Abstract

Low-grade fibromyxoid sarcoma (LGFMS) is a rare low-grade malignant fibroblastic tumor, harboring a characteristic FUS-CREB3L2 or FUS-CREB3L1 gene fusion. The authors presented 10 genetically confirmed cases in a Chinese population. To the best of our knowledge, the present series consists of the most genetically confirmed cases from a Chinese medical center in English literature. The clinical, histologic, immunohistochemical, and molecular features of all cases are reviewed. The age of the patients (7 females, 3 males) ranged from 4 to 58 years old (median, 26 y; mean, 27 y). Trunk (4/10, 40%) was the most common site. Microscopically, all the cases exhibited an admixture of myxoid nodules and fibrous zones. The tumor cells were deceptively bland and nuclear pleomorphism was observed in focal areas of one case. Immunohistochemically, neoplastic cells were focally reactive for EMA (1/9, 11.1%), and negative for S-100 protein, CD34, smooth muscle actin, and desmin (0/9). Of the 4 cases stained with MUC4, one showed focal expression and others were interpreted as indeterminate. Surgical excision was performed for all patients. Follow-up information was available for 8 cases, and none developed local recurrence or metastasis at last follow-up (mean 31 months). LGFMS is a distinctive low-grade malignant tumor. The diagnosis of this tumor might be very challenging and it is mistaken for many benign lesions. A combination of clinical studies, careful morphologic analysis, and a full panel of immunomarkers especially genetic studies is helpful in confirming the diagnosis. This tumor type is associated with favorable prognosis.

Keywords: FUS rearrangement; Low-grade fibromyxoid sarcoma; fluorescence in situ hybridization.

Figure 1

A. LGFMS with abrupt transition from fibrous to myxoid zones (×40); B. LGFMS with classic features of spindle-shaped cells with a bland appearance scattered in alternating fibrous and myxoid areas (×200). C. Spindle tumor cells of LGFMS arranged in an apparent whorled growth pattern (×200). D. Typical curvilinear vessels in myxoid areas of LGFMS (×200). E. Arcades of curvilinear vessels in the myxoid zone of LGFMS (×200). F. Increased perivascular cellularity in the myxoid zone of LGFMS (×200).

Figure 2

A. A region displayed evident nuclear pleomorphism and atypia (upper left) in contrast to a classic histologic feature (lower right) of LGFMS (×100). A region with predominant nuclear atypia and evident nuclear pleomorphism. B. (×200). C. (×400).

Figure 3

LGFMS with focal area of SEF-like morphology. A. (×100). B. (×200).

Figure 4

FUS gene rearrangement (marked with yellow arrow) was positively detected by FISH analysis.