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Myxoinflammatory Fibroblastic Sarcoma, Nodular-Necrotizing Variant With Two YAP1::MAML2 Fusions and TRIM24::BRAF

Kim Harnisch1,2, Beata Bode3, Obinna Chijioke4

  • 1Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

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|August 18, 2025
PubMed
Summary

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare cancer. This study identifies novel gene fusions, YAP1::MAML2 and TRIM24::BRAF, expanding the understanding of MIFS genetic diversity and potential therapeutic targets.

Keywords:
TRIM24::BRAF fusionYAP1::MAML2 fusionmyxoinflammatory fibroblastic sarcomanodular-necrotizing variant

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Area of Science:

  • Oncology
  • Pathology
  • Genetics

Background:

  • Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue neoplasm.
  • MIFS typically presents in adults with characteristic histological features and known genetic alterations like TGFBR3-MGEA5 rearrangements.
  • YAP1::MAML2 fusions have been recently identified in specific variants of MIFS.

Purpose of the Study:

  • To report a novel case of MIFS with unusual genetic findings.
  • To expand the known molecular spectrum of MIFS.
  • To investigate potential new therapeutic targets in MIFS.

Main Methods:

  • Histopathological examination of a tumor sample.
  • Immunohistochemical analysis.
  • Next-generation sequencing for molecular genetic testing to identify gene fusions.

Main Results:

  • A case of MIFS in a 40-year-old male presenting with thumb pain was analyzed.
  • Molecular genetic testing revealed two variants of YAP1::MAML2 gene fusions and a novel TRIM24::BRAF fusion.
  • Immunohistochemistry was negative for common sarcoma markers.

Conclusions:

  • This case presents a unique molecular profile for MIFS, including the novel TRIM24::BRAF fusion.
  • The findings highlight the genetic heterogeneity of MIFS.
  • The identified gene fusions, particularly TRIM24::BRAF, may represent potential therapeutic targets requiring further investigation.