Novel EVI5::BRAF Gene Fusion in Infantile Fibrosarcoma: A Case Report and Review of Literature

Autores de IIS La Fe

• Judith González López

  Autor

• Luis Alberto Rubio Martinez

  Autor

• Miryam Atares Huerta

  Autor

• José Vicente Amaya Valero

  Autor

• Maria Carmen Huart Peris

  Autor

• Empar Mayordomo Aranda

  Autor

• Francisco Giner Segura

  Autor

Grupos

• Cirugía digestiva y Cuidados perioperatorios

• Cirugía Ortopédica y Traumatología

• Grupo de Investigación en tumores ginecológicos, cáncer de mama y cáncer hereditario

• Hemostasia, Trombosis, Arteriosclerosis y Biología vascular

Abstract

Infantile Fibrosarcoma is a malignant tumor of fibroblastic origin, typically found in early childhood, locally aggressive, and characterized by molecular alterations that activate tyrosine kinase signaling, primarily the ETV6::NTRK3 fusion. In recent years, a series of fusions different from the classic one have been described, including NTRK1, RAF1, and BRAF. In this paper, we present a case of IFS with a novel EVI5::BRAF fusion. We observed a spindle cell neoplasm growing in intertwined fascicles within a fibrous stroma, without the formation of an immature osteoid matrix. Weak and focal immunoreactivity for S100 was observed. SATB2 exhibited diffuse and intense staining, with focal expression of osteonectin and negativity for caldesmon, Smooth Muscle Actin, desmin, GFAP, SOX10, MelanA, panTRK, and HMB45. The Ki67 index was 7%, and the tumor harbored an EVI5::BRAF genetic fusion. To the best of our knowledge, the EVI5::BRAF fusion has not yet been described in BRAF fusions in IFS. Nevertheless, further studies are needed to define the prognostic features of these emerging BRAF sarcomas, along with new anti-BRAF therapeutic approaches. © 2025 by the authors.

Keywords

• Female; Fibrosarcoma; Gene Fusion; Humans; Infant; Male; Oncogene Proteins, Fusion; Proto-Oncogene Proteins B-raf; Transcription Factors; B Raf kinase; caldesmon; glial fibrillary acidic protein; Ki 67 antigen; melan A; osteonectin; protein S 100; protein tyrosine kinase; smooth muscle actin; transcription factor Sox10; B Raf kinase; BRAF protein, human; oncogene fusion protein; transcription factor; accidental injury; adolescent; aneurysmal bone cyst; arm pain; Article; bone matrix; case report; clinical article; computer assisted tomography; congenital infantile fibrosarcoma; differential diagnosis; emergency care; Ewing sarcoma; fibrous dysplasia; fibula graft; fluorescence in situ hybridization; gene fusion; high throughput sequencing; human; human tissue; immunohistochemistry; immunoreactivity; in vitro study; male; medical literature; needle biopsy; nuclear magnetic resonance imaging; osteoid; osteosarcoma; protein expression; proximal humerus fracture; staining; stroma; tumor-fr