A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: A pathologic and molecular study of 18 cases

• Published in: Genes chromosomes & cancer Vol. 54; no. 1; pp. 28 - 38
• Main Authors: Prieto-Granada, Carlos, Zhang, Lei, Chen, Hsiao-Wei, Sung, Yun-Shao, Agaram, Narasimhan P, Jungbluth, Achim A, Antonescu, Cristina R
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.01.2015; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Calmodulin-Binding Proteins - genetics; Calmodulin-Binding Proteins - metabolism; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Female; Fibrosarcoma - genetics; Fibrosarcoma - metabolism; Fibrosarcoma - pathology; Gene Fusion; Humans; Male; Middle Aged; Mucin-4 - genetics; Mucin-4 - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; RNA-Binding Protein EWS; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sarcoma - genetics; Sarcoma - metabolism; Sarcoma - pathology; Sclerosis; Young Adult
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.22215

Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low‐grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS‐CREB3L1 fusion, both FUS‐CREB3L2 and EWSR1‐CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS‐CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow‐up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS‐tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by fluorescence in situ hybridization with only one case exhibiting FUS rearrangement. Of the nine EWSR1 positive cases, six cases harbored CREB3L1 break‐apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS‐CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS. © 2014 Wiley Periodicals, Inc.