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Adamantinoma-like Ewing Sarcoma (ALES) May Harbor FUS Rearrangements : A Potential Diagnostic Pitfall.

Doreen N Palsgrove1, Robert D Foss2, Wengdong Yu3

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The American Journal of Surgical Pathology
|July 26, 2023
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Summary

This study identifies FUS rearrangements in EWSR1-negative Adamantinoma-like Ewing sarcoma (ALES), expanding diagnostic possibilities. It highlights unusual features and introduces FUS::FLI1 fusion in this rare cancer.

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Area of Science:

  • Oncology
  • Pathology
  • Molecular Diagnostics

Background:

  • Adamantinoma-like Ewing sarcoma (ALES) is a rare malignancy, typically associated with EWSR1 rearrangements.
  • Understanding genetic alterations in EWSR1-negative ALES is crucial for accurate diagnosis and treatment.

Purpose of the Study:

  • To investigate the molecular and clinicopathological features of EWSR1-negative ALES.
  • To expand the diagnostic considerations for ALES, particularly concerning FUS rearrangements and novel fusion genes.

Main Methods:

  • Histopathological and immunohistochemical analysis of 6 EWSR1-negative ALES cases.
  • Molecular testing including FISH and RT-PCR for gene rearrangements and fusions.

Main Results:

  • All 6 cases of EWSR1-negative ALES harbored FUS rearrangements, with FEV or FLI1 as gene partners.
  • A novel FUS::FLI1 fusion was identified, previously unreported in Ewing family tumors.
  • Histological and immunophenotypic overlap with neuroendocrine tumors and olfactory carcinoma was observed.

Conclusions:

  • FUS rearrangements are a key molecular event in a subset of ALES, broadening diagnostic criteria.
  • The identification of FUS::FLI1 fusion expands the known molecular landscape of Ewing family tumors.
  • ALES can present with diverse histological and immunophenotypic features, necessitating comprehensive diagnostic workup including molecular testing.