Sclerosing epithelioid fibrosarcoma of bone: morphological, immunophenotypical, and molecular findings of 9 cases

• Published in: Virchows Archiv : an international journal of pathology 2021-04, Vol.478 (4), p.767-777
• Main Authors: Kosemehmetoglu, Kemal, Ardic, Fisun, Kilpatrick, Scott E., Aydingoz, Ustun, Sumathi, Vaiyapuri P., Michal, Michael
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical materials; Bone cancer; Bone Neoplasms - diagnosis; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Bone tumors; Bones; Chondrosarcoma; Female; Fibrosarcoma; Fibrosarcoma - diagnosis; Fibrosarcoma - genetics; Fibrosarcoma - metabolism; Fibrosarcoma - pathology; FLI-1 protein; Follow-Up Studies; FUS gene; Gene fusion; Gene Rearrangement; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Long bone; Male; Matrix Attachment Region Binding Proteins - metabolism; Medicine; Medicine & Public Health; Metastases; Middle Aged; Morphology; Neoplasia; Neoplasm Metastasis; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Next-generation sequencing; Original Article; Osteoid; Osteosarcoma; Pathology; Phenotype; Radiology; Sarcoma; Soft tissues; Stellate cells; Stroma; Transcription Factors - metabolism; Tumors; Young Adult
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-020-02953-y

Primary sclerosing epithelioid fibrosarcoma (SEF) of bone is a rare and scarcely reported neoplasm. We document clinicopathological and molecular features of 9 additional cases. Five males and 4 females had a mean age of 39 years (14–71 years). Most tumors affected flat/irregular bones; only 3 cases involved a long bone. By radiology, it has characteristic radiographic features of a predominantly lytic expansile lesion with a sclerotic rim. Referring diagnoses were SEF ( n = 2), low-grade osteosarcoma ( n = 2), chondrosarcoma ( n = 1), and chondromyxoid fibroma ( n = 1). Histologically, five cases revealed classical morphology of SEF of soft tissue. Remaining cases were classified as hybrid SEF/low-grade fibromyxoid sarcoma, characterized by spindle or stellate cells, prominent stroma, and giant hyalinized areas. Various morphological deviations such as prominent vasculature ( n = 3), osteoid-like material ( n = 4), or parallel bone trabeculae ( n = 2) were observed. Immunohistochemically, all cases showed diffuse and strong MUC4 expression. SATB2 was observed in 5/8 cases. Using FISH, EWSR1 , and FUS rearrangements were detected in 4 cases and 1 case, respectively. EWSR1-CREB3L1 fusion was identified in 1 additional case by next-generation sequencing. Recurrence and metastasis were observed in 1 case and 2 cases, respectively. All but one patient were alive with disease for a mean interval of 31 months. SEF of bone is a relatively indolent sarcoma of adults, most commonly located in the flat/irregular bones. Due to overlapping histological features, it is often misdiagnosed as osteosarcoma or a chondroid tumor. Most SEF of bone exhibit EWSR1 rearrangements, but rare cases may harbor a FUS gene fusion.