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Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement

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Abstract

Background

Sinonasal adenosquamous carcinoma is rare, and there are almost no studies detailing morphology or characterizing their genetic driver events. Further, many authors have termed sinonasal tumors with combined squamous carcinoma and glands as mucoepidermoid carcinoma but none have analyzed for the presence of MAML2 rearrangement.

Methods

Cases from 2014 to 2020 were collected and diagnosed using World Health Organization criteria. They were tested for p16 expression by immunohistochemistry (70% cut-off), DEK::AFF2 fusion by fluorescence in situ hybridization (FISH) and AFF2 immunohistochemistry, MAML2 rearrangement by FISH, and low- and high-risk HPV by RNA ISH and reverse transcription PCR, respectively. Detailed morphology and clinical features were reviewed.

Results

There were 7 male (64%) and 4 female (36%) patients with a median age of 69 years, most Caucasian (10 of 11 or 91%). Most had tobacco exposure (8/11, 73%) and most presented with epistaxis, a visible nasal mass, and/or facial pain. Several had a precursor papillomas (3 of 11, 27%). The squamous component had variable keratinization, 5 of 11 (46%) of which would be described as keratinizing, 3 non-keratinizing, and 2 with mixed features. All had gland formation, by definition, and 2 of 11 (18%) had ciliated tumor cells. None of the 11 cases had MAML2 rearrangement and one had DEK::AFF2 fusion with associated positive nuclear AFF2 protein immunostaining. Most were p16 positive (7 of 11, 64%) and all 7 of these were hrHPV positive either by RNA ISH or RT-PCR. Two of the p16-negative tumors were positive for lrHPV by RNA ISH. Treatment included surgery alone (4 of 11, 36%), surgery with adjuvant radiation (5 of 11, 45%), and surgery with radiation and chemotherapy (2 of 11, 18%). Four of 11 patients (36%) suffered disease recurrence, two requiring re-operation and who were disease free at last follow-up, one receiving additional chemotherapy and who was alive with disease. The other elected to undergo palliative therapy and died of disease.

Conclusion

Sinonasal adenosquamous carcinoma is a somewhat heterogeneous tumor not infrequently arising ex papilloma and having various drivers including high- and low-risk HPV and rarely DEK::AFF2 fusion. The prognosis appears favorable when proper treatment is possible.

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Data Availability

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Acknowledgements

The authors would like to thank the staff of the Tissue Pathology Shared Resource (TPSR) for the excellent work on the immunostains used in this study.

Funding

Research was performed using discretionary funds from the Department of Pathology, Microbiology, and Immunology. The work also utilized the Translational Pathology Shared Resource (TPSR) at Vanderbilt University Medical Center which is supported by the NCI/NIH Cancer Center Support Grant 5P30 CA68485-19 and the Shared Instrumentation Grant S10 OD023475.

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Authors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

    Dean Holliday Jr., Mitra Mehrad, Kim A. Ely & James S. Lewis Jr.

  2. Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Fangjia Tong & Xiaowei Wang

  3. University of Illinois Cancer Center, Chicago, IL, USA

    Xiaowei Wang

  4. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Jen-Fan Hang & Ying-Ju Kuo

  5. School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Jen-Fan Hang & Ying-Ju Kuo

  6. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Jen-Fan Hang

  7. Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, USA

    Jaylou M. Velez-Torres

  8. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Abberly Lott-Limbach

  9. Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    James S. Lewis Jr.

  10. Vanderbilt University Hospital, 1211 Medical Center Drive, Room 3020D Surgical Pathology, Nashville, TN, 37232, USA

    James S. Lewis Jr.

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  1. Dean Holliday Jr.
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Contributions

All authors whose names appear on the submission made substantial contributions to the conception or design of the work, to the acquisition, analysis, or interpretation of data, and/or drafted the work or revised it critically for important intellectual content including approving the version to be published. They agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to James S. Lewis Jr..

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was performed with approval of the institutional review boards of Vanderbilt University Medical Center and complies with required ethical standards. Given the retrospective nature of the study, with consultation with the institutional review boards, it was determined that the study did not need ethical approval. Patients were never contacted, and we did not require informed consent or specific consent to publish.

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Holliday, D., Mehrad, M., Ely, K.A. et al. Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement. Head and Neck Pathol 17, 487–497 (2023). https://doi.org/10.1007/s12105-023-01538-w

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