Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”

BackgroundDEK::AFF2 fusion-associated carcinomas of the sinonasal tract are exceedingly rare, with fewer than 100 cases reported worldwide, but probably underrecognized. Recently classified by the WHO as a distinct provisional subtype of non-keratinizing squamous cell carcinoma, these tumors pose si...

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Main Authors: Moritz Knebel, Abbas Agaimy, Jan Philipp Kühn, Sandrina Körner, Felix Braun, Lukas Brust, Veronika Flockerzi, Silke Wemmert, Benedikt Balensiefer, Bernhard Schick, Umut Yilmaz, Malek Zaito, Alessandro Bozzato, Maximilian Linxweiler
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1611790/full
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author Moritz Knebel
Moritz Knebel
Abbas Agaimy
Jan Philipp Kühn
Jan Philipp Kühn
Sandrina Körner
Sandrina Körner
Felix Braun
Felix Braun
Lukas Brust
Lukas Brust
Veronika Flockerzi
Veronika Flockerzi
Silke Wemmert
Silke Wemmert
Benedikt Balensiefer
Benedikt Balensiefer
Bernhard Schick
Umut Yilmaz
Umut Yilmaz
Malek Zaito
Malek Zaito
Alessandro Bozzato
Alessandro Bozzato
Maximilian Linxweiler
Maximilian Linxweiler
author_facet Moritz Knebel
Moritz Knebel
Abbas Agaimy
Jan Philipp Kühn
Jan Philipp Kühn
Sandrina Körner
Sandrina Körner
Felix Braun
Felix Braun
Lukas Brust
Lukas Brust
Veronika Flockerzi
Veronika Flockerzi
Silke Wemmert
Silke Wemmert
Benedikt Balensiefer
Benedikt Balensiefer
Bernhard Schick
Umut Yilmaz
Umut Yilmaz
Malek Zaito
Malek Zaito
Alessandro Bozzato
Alessandro Bozzato
Maximilian Linxweiler
Maximilian Linxweiler
author_sort Moritz Knebel
collection DOAJ
description BackgroundDEK::AFF2 fusion-associated carcinomas of the sinonasal tract are exceedingly rare, with fewer than 100 cases reported worldwide, but probably underrecognized. Recently classified by the WHO as a distinct provisional subtype of non-keratinizing squamous cell carcinoma, these tumors pose significant diagnostic and therapeutic challenges. Their histological resemblance to inverted papillomas and their bland histology in most cases often leads to misdiagnosis, while their aggressive behavior underscores the need for a tailored treatment approach.Case presentationWe report two cases of DEK::AFF2 fusion-associated carcinomas managed at Saarland University Medical Center. The first case involved a 46-year-old woman who initially presented with recurrent sinonasal inverted papilloma, confirmed through multiple surgical interventions over nearly a decade. In 2023, reevaluation and genetic analysis revealed a DEK::AFF2 fusion. The patient demonstrated an exceptional response to three cycles of neoadjuvant gemcitabine and cisplatin, achieving complete remission on MRI restaging. This allowed a shift to definitive chemoradiotherapy, with sustained disease-free status confirmed by a PET-CT three months post-treatment in July 2024. The second case involved a 66-year-old woman presenting with recurrent inverted papilloma affecting the sinonasal and tympanic regions. Despite multiple surgeries, malignant transformation to invasive squamous cell carcinoma occurred, with lymph node metastasis and intracranial spread. A combined otolaryngological and neurosurgical approach was undertaken, but the disease progressed. The patient passed away in January 2020, with postmortem review of the prior histology and genetic analysis confirming DEK::AFF2 fusion carcinoma that showed bland-looking papilloma-like morphology in the initial specimens and later a high-grade cytology indicating biological progression to poorly differentiated carcinoma.ConclusionThese cases highlight the aggressive nature of DEK::AFF2 fusion-associated carcinomas and the critical role of genetic profiling in diagnosis and management. The exceptional, first ever reported response to neoadjuvant chemotherapy in one case underscores the potential for personalized treatment strategies, warranting further investigation into targeted therapies for this rare malignancy.
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series Frontiers in Immunology
spelling doaj-art-86d01b0f48d94172879f4bc98de5572d2025-08-20T03:29:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16117901611790Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”Moritz Knebel0Moritz Knebel1Abbas Agaimy2Jan Philipp Kühn3Jan Philipp Kühn4Sandrina Körner5Sandrina Körner6Felix Braun7Felix Braun8Lukas Brust9Lukas Brust10Veronika Flockerzi11Veronika Flockerzi12Silke Wemmert13Silke Wemmert14Benedikt Balensiefer15Benedikt Balensiefer16Bernhard Schick17Umut Yilmaz18Umut Yilmaz19Malek Zaito20Malek Zaito21Alessandro Bozzato22Alessandro Bozzato23Maximilian Linxweiler24Maximilian Linxweiler25Institute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (CCC ER-EMN), Erlangen, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartement of Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Diagnostic and Interventional Neuroradiology, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartement of Nuclear Medicine, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyInstitute of Otorhinolaryngology, Saarland University, Homburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, GermanyBackgroundDEK::AFF2 fusion-associated carcinomas of the sinonasal tract are exceedingly rare, with fewer than 100 cases reported worldwide, but probably underrecognized. Recently classified by the WHO as a distinct provisional subtype of non-keratinizing squamous cell carcinoma, these tumors pose significant diagnostic and therapeutic challenges. Their histological resemblance to inverted papillomas and their bland histology in most cases often leads to misdiagnosis, while their aggressive behavior underscores the need for a tailored treatment approach.Case presentationWe report two cases of DEK::AFF2 fusion-associated carcinomas managed at Saarland University Medical Center. The first case involved a 46-year-old woman who initially presented with recurrent sinonasal inverted papilloma, confirmed through multiple surgical interventions over nearly a decade. In 2023, reevaluation and genetic analysis revealed a DEK::AFF2 fusion. The patient demonstrated an exceptional response to three cycles of neoadjuvant gemcitabine and cisplatin, achieving complete remission on MRI restaging. This allowed a shift to definitive chemoradiotherapy, with sustained disease-free status confirmed by a PET-CT three months post-treatment in July 2024. The second case involved a 66-year-old woman presenting with recurrent inverted papilloma affecting the sinonasal and tympanic regions. Despite multiple surgeries, malignant transformation to invasive squamous cell carcinoma occurred, with lymph node metastasis and intracranial spread. A combined otolaryngological and neurosurgical approach was undertaken, but the disease progressed. The patient passed away in January 2020, with postmortem review of the prior histology and genetic analysis confirming DEK::AFF2 fusion carcinoma that showed bland-looking papilloma-like morphology in the initial specimens and later a high-grade cytology indicating biological progression to poorly differentiated carcinoma.ConclusionThese cases highlight the aggressive nature of DEK::AFF2 fusion-associated carcinomas and the critical role of genetic profiling in diagnosis and management. The exceptional, first ever reported response to neoadjuvant chemotherapy in one case underscores the potential for personalized treatment strategies, warranting further investigation into targeted therapies for this rare malignancy.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1611790/fullDEK::AFF2 fusionsinonasal cancerneoadjuvant chemo(radio)therapyprognosisdiagnostic
spellingShingle Moritz Knebel
Moritz Knebel
Abbas Agaimy
Jan Philipp Kühn
Jan Philipp Kühn
Sandrina Körner
Sandrina Körner
Felix Braun
Felix Braun
Lukas Brust
Lukas Brust
Veronika Flockerzi
Veronika Flockerzi
Silke Wemmert
Silke Wemmert
Benedikt Balensiefer
Benedikt Balensiefer
Bernhard Schick
Umut Yilmaz
Umut Yilmaz
Malek Zaito
Malek Zaito
Alessandro Bozzato
Alessandro Bozzato
Maximilian Linxweiler
Maximilian Linxweiler
Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”
Frontiers in Immunology
DEK::AFF2 fusion
sinonasal cancer
neoadjuvant chemo(radio)therapy
prognosis
diagnostic
title Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”
title_full Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”
title_fullStr Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”
title_full_unstemmed Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”
title_short Case Report: “DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies”
title_sort case report dek aff2 fusion associated sinonasal carcinomas a novel oncogenic driver and emerging therapeutic strategies
topic DEK::AFF2 fusion
sinonasal cancer
neoadjuvant chemo(radio)therapy
prognosis
diagnostic
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1611790/full
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