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Unclassified Neuroendocrine Tumor with a Novel CHD4::AFF2 Fusion: Expanding the Family of AFF2-Rearranged Head and Neck Malignancies

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Abstract

The past decade has seen a dramatic increase in the number of new head and neck tumor entities, most of which are genetically defined. DEK::AFF2 carcinoma is one of the most recently defined neoplasms; it shows a non-keratinizing squamous morphology and occurs in the sinonasal region. We present an unusual neoplasm that was found to harbor a novel fusion involving AFF2. The case was encountered in our clinical practice. Immunohistochemistry was performed along with targeted next generation sequencing (NGS). The case presented as a metastasis to a cervical lymph node from an unknown primary, in a 49-year-old man. The tumor consisted of sheets of primitive round cells which were strongly positive for synaptophysin and chromogranin but negative for cytokeratins, S-100 protein, WT-1, desmin, and many other markers. NGS uncovered CHD4::AFF2. We found a CHD4::AFF2 fusion in a high-grade neuroendocrine tumor. Although it is just a single case, the presence of a novel fusion in a neoplasm that is otherwise not classifiable suggests that it could be a distinct entity within a possible family of AFF2-rearranged tumors. Molecular analysis should be considered for any unclassified round cell tumor in the head and neck, as additional cases will be needed to further elucidate this area.

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Availability of data and material is possible upon reasonable request, deidentified for maintenance of anonymity and compliance with IRB approval.

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Funding

This study was funded by the Jane B. and Edwin P. Jenevein Endowment for Pathology at UT Southwestern Medical Center. No external funding was obtained for this study.

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Authors and Affiliations

  1. Department of Pathology, Saint Louis University School of Medicine, St Louis, MO, USA

    Daniel L. Miller, Anu Rijal & Vivan Hathuc

  2. Department of Pathology, University of Texas Southwestern Medical Center, 6201 Harry Hines Blvd, Dallas, TX, USA

    Doreen N. Palsgrove, Jeffrey Gagan & Justin A. Bishop

  3. Department of Pathology and Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine, St Louis, MO, USA

    Rebecca Chernock

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  1. Daniel L. Miller
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  2. Doreen N. Palsgrove
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  3. Anu Rijal
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  6. Jeffrey Gagan
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  7. Justin A. Bishop
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All authors confirm they have meaningfully contributed to the research and read and approved the final manuscript.

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Correspondence to Justin A. Bishop.

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All procedures performed in this retrospective data analysis involving human participants were in accordance with the ethical standards of the institutional review board (IRB 112017–073), which did not require informed consent.

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Miller, D.L., Palsgrove, D.N., Rijal, A. et al. Unclassified Neuroendocrine Tumor with a Novel CHD4::AFF2 Fusion: Expanding the Family of AFF2-Rearranged Head and Neck Malignancies. Head and Neck Pathol 16, 928–933 (2022). https://doi.org/10.1007/s12105-022-01432-x

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