Clinical and molecular characterization of primary sclerosing epithelioid fibrosarcoma of bone and review of the literature

Abstract

Sclerosing epithelioid fibrosarcoma (SEF) is a rare sarcoma subtype characterized by monomorphic epithelioid cells embedded in a densely sclerotic collagenous matrix.The overwhelming majority of tumors arise in soft tissues; however, rare cases have been documented to occur primarily in bone. The hallmarks of soft tissue SEF include MUC4 immunoreactivity and the presence of an EWSR1-CREB3L1 fusion. Rare cases with alternative fusions have also been reported such as EWSR1-CREB3L2 and FUS-CREB3L2 transcripts. The molecular alterations of skeletal SEF have not been welldefined, with only rare cases analyzed to date. In this study we investigated the clinicopathologic and molecular features of seven patients presenting with primary osseous SEF. There were 3 males and 4 females, with a mean age at diagnosis of 38 years. All cases had microscopic features within the histologic spectrum of SEF and showed strong and diffuse MUC4 positivity, while lacking SATB2 expression.However, due to its unusual presentation within bone, four cases were initially misinterpreted as either osteosarcoma, Ewing sarcoma or chondroblastoma. Half of the patients with follow-up data developed metastasis. The cases were tested by targeted RNA sequencing, MSK-IMPACT, and/or fluorescence in situ hybridization, showing EWSR1-CREB3L1 in six cases and EWSR1-CREB3L2 in one case. The fusion transcripts were composed of EWSR1 exon 11 to either exon 6 of CREB3L1 or CREB3L2. In summary, due to their rarity in the bone, skeletal SEF are often misdiagnosed, resulting in inadequate treatment modalities. Similar to their soft tissue counterpart, bone SEF follow an aggressive clinical behavior and show similar EWSR1-CREB3L1/CREB3L2 fusions. K E Y W O R D S CREB3L1, CREB3L2, EWSR1, fusions, sclerosing epithelioid fibrosarcoma

Case Report: Radiological Features of Sclerosing Epithelioid Fibrosarcoma in the Right Fibula

“…Primary osseous SEF usually manifested as a well-demarcated, heterogeneous, osteolytic mass with bone destruction on CT (10,13). The mass typically presented a sharp border without obvious periosteal reaction (10,13). In the present case, the osteolytic lesion also presented a well-demarcated sharp border with slight periosteal reaction.…”

“…this case report, we firstly give a comprehensive radiological description of fibula SEF, including CT and MR findings. Primary osseous SEF usually manifested as a well-demarcated, heterogeneous, osteolytic mass with bone destruction on CT (10,13). The mass typically presented a sharp border without obvious periosteal reaction (10,13).…”

“…And it is exceedingly rare which may cause diagnostic pitfalls radiologically. Only dozens of cases of primary SEF in the bone have been reported so far (10)(11)(12)(13)(14), without case involving fibula reported in literature to date. Herein we report the first case of primary SEF in the right fibula in a 19-year-old man.…”

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“…To the best of our knowledge, this case is the first reported case of primary SEF in the fibula. Primary osseous SEF mainly affects patients with a mean age of 45 years and has no gender predilection (10). Nevertheless, this patient was a 19year-old young man.…”

“…There were 6 cases in the femur, 2 cases in the ulna, 1 case in the humerus, 1 case in the tibia and 1 case in the fibula. Of these cases, only 3 cases showed CT and/or MR images (10,14,16). In , and hypo-and hyperintense mixed mass on T2-weighted image (B).…”