PMID- 36849671 OWN - NLM STAT- MEDLINE DCOM- 20230628 LR - 20240410 IS - 1936-0568 (Electronic) IS - 1936-055X (Print) IS - 1936-055X (Linking) VI - 17 IP - 2 DP - 2023 Jun TI - Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement. PG - 487-497 LID - 10.1007/s12105-023-01538-w [doi] AB - 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. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Holliday, Dean Jr AU - Holliday D Jr AD - Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Mehrad, Mitra AU - Mehrad M AD - Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Ely, Kim A AU - Ely KA AD - Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Tong, Fangjia AU - Tong F AD - Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA. FAU - Wang, Xiaowei AU - Wang X AD - Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA. AD - University of Illinois Cancer Center, Chicago, IL, USA. FAU - Hang, Jen-Fan AU - Hang JF AD - Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. AD - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Kuo, Ying-Ju AU - Kuo YJ AD - Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Velez-Torres, Jaylou M AU - Velez-Torres JM AD - Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Lott-Limbach, Abberly AU - Lott-Limbach A AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA. FAU - Lewis, James S Jr AU - Lewis JS Jr AUID- ORCID: 0000-0001-9002-1283 AD - Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. james.lewis@vumc.org. AD - Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. james.lewis@vumc.org. AD - Vanderbilt University Hospital, 1211 Medical Center Drive, Room 3020D Surgical Pathology, Nashville, TN, 37232, USA. james.lewis@vumc.org. LA - eng GR - P30 CA068485/CA/NCI NIH HHS/United States GR - R01 DE026471/DE/NIDCR NIH HHS/United States GR - S10 OD023475/OD/NIH HHS/United States GR - S10 OD023475/NR/NINR NIH HHS/United States PT - Journal Article DEP - 20230228 PL - United States TA - Head Neck Pathol JT - Head and neck pathology JID - 101304010 RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Nuclear Proteins) RN - 0 (AFF2 protein, human) RN - 0 (MAML2 protein, human) RN - 0 (Trans-Activators) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - *Carcinoma, Adenosquamous/pathology MH - Human Papillomavirus Viruses MH - RNA, Messenger MH - In Situ Hybridization, Fluorescence MH - *Papillomavirus Infections/complications MH - Transcription Factors/genetics MH - Nuclear Proteins/genetics MH - *Paranasal Sinus Neoplasms/genetics/pathology MH - *Carcinoma, Mucoepidermoid/pathology MH - Trans-Activators/genetics PMC - PMC10293130 OTO - NOTNLM OT - Adenosquamous Carcinoma OT - DEK::AFF2 OT - High-risk HPV OT - Low-risk HPV OT - MAML2 OT - Nasal Cavity OT - Paranasal Sinus COIS- The authors declare that they have no conflicts of interest as it relates to this work. EDAT- 2023/03/01 06:00 MHDA- 2023/06/28 06:42 PMCR- 2024/02/28 CRDT- 2023/02/28 00:06 PHST- 2022/12/14 00:00 [received] PHST- 2023/01/16 00:00 [accepted] PHST- 2023/06/28 06:42 [medline] PHST- 2023/03/01 06:00 [pubmed] PHST- 2023/02/28 00:06 [entrez] PHST- 2024/02/28 00:00 [pmc-release] AID - 10.1007/s12105-023-01538-w [pii] AID - 1538 [pii] AID - 10.1007/s12105-023-01538-w [doi] PST - ppublish SO - Head Neck Pathol. 2023 Jun;17(2):487-497. doi: 10.1007/s12105-023-01538-w. Epub 2023 Feb 28.