The pathology of reactive, dysplastic, and neoplastic sinonasal seromucinous glands is complex, and their contribution to tumorigenesis of sinonasal carcinomas remains controversial. In our practice, we have observed the presence of respiratory epithelial adenomatoid hamartomas (REAH) and seromucinous hamartomas (SH) associated with adenoid cystic carcinomas (AdCC) in a subset of cases. In many of these cases, genuine atypical features and dysplastic characteristics of the glands were noted at the interface of SH and AdCC. To investigate this phenomenon further, 88 sinonasal AdCC cases were selected from the authors' files and analyzed histologically, immunohistochemically, and genetically searching for MYB/MYBL1 and NFIB gene fusions. HPV testing was also performed. Univariate statistical analysis was conducted on our cohort. Thirty-one cases (35%) showed features of atypical sinonasal glands arising in SH (ASGSH) at the SH-AdCC interface, characterized by bilayered epithelium, architectural disarray, mild nuclear polymorphism, and atypia, sometimes with colloid-like material in the lumen. The MYB immunomarker was negative in 14 ASGSHs (with a positive internal control in AdCC cells), while only two cases showed faint and moderate to weak expression of the antibody in ASGSH glands. In 12 cases, the immunostaining of ASGSH could not be properly assessed, while AdCC cells were negative. The immunostaining was not performed in five cases. Our findings suggest that a subset of sinonasal AdCC may originate in a multistep dysplastic process within SH, consistent with an SH-ASGSH-AdCC progression sequence.

Bioptic Laboratory Ltd Plzen Czech Republic

Consultoria Em Patologia Botucatu São Paulo Brazil

Department of Otorhinolaryngology and Head and Neck Surgery University Hospital Erlangen Erlangen Germany

Department of Otorhinolaryngology Turku University Hospital Turku Finland

Department of Pathology and Laboratory Medicine The University of Kansas School of Medicine Kansas City KS USA

Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland

Department of Pathology Medical University of Vienna Vienna Austria

Department of Pathology Tenon Hospital Sorbonne University Paris France

Department of Pathology Turku University Hospital Turku Finland

Dermpath Muenchen Germany

Institute of Biomedicine Pathology University of Turku Turku Finland

Institute of Pathology University Hospital Erlangen Friedrich Alexander University Erlangen Nürnberg Erlangen EMN Erlangen Germany

Molecular and Genetic Laboratory Bioptic Laboratory Ltd Plzen Czech Republic

Service d'Anatomo Pathologie Department of Pathology Hôpital Européen G Pompidou APHP Université de Paris 20 40 Rue Leblanc 75015 Paris France

Sikl's Department of Pathology Charles University Faculty of Medicine in Plzen E Benese 13 305 99 Pilsen Czech Republic

The Fingerland Department of Pathology Charles University Faculty of Medicine and University Hospital Hradec Kralove Czechia Czech Republic

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Thompson LD, Penner C, Ho NJ et al (2014) Sinonasal tract and nasopharyngeal adenoid cystic carcinoma: a clinicopathologic and immunophenotypic study of 86 cases. Head Neck Pathol 8:88–109 PubMed PMC

WHO Classification of Tumours Editorial Board. Head and neck tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2023 [cited 2025/01/11]. (WHO classification of tumours series, 5th ed.; vol. 9). Available from: https://tumourclassification.iarc.who.int/chapters/52.

Du F, Zhou CX, Gao Y (2016) Myoepithelial differentiation in cribriform, tubular and solid pattern of adenoid cystic carcinoma: a potential involvement in histological grading and prognosis. Ann Diagn Pathol 22:12–17 PubMed

Weinreb I, Rooper LM, Dickson BC et al (2023) Adenoid cystic carcinoma with striking tubular hypereosinophilia: a unique pattern associated with nonparotid location and both canonical and novel EWSR1::MYB and FUS::MYB Fusions. Am J Surg Pathol 47:497–503 PubMed

Altemani A, Costa AF, Montalli VA et al (2013) Signet-ring cell change in adenoid cystic carcinoma: a clinicopathological and immunohistochemical study of four cases. Histopathology 62:531–542 PubMed

Ooms KDW, Chiosea S, Lamarre E et al (2023) Sebaceous differentiation as another feature of metatypical adenoid cystic carcinoma: a case report and letter to the editor. Am J Surg Pathol 47:145–146 PubMed

Mathew EP, Todorovic E, Truong T et al (2022) Metatypical adenoid cystic carcinoma: a variant showing prominent squamous differentiation with a predilection for the sinonasal tract and skull base. Am J Surg Pathol 46:816–822 PubMed

Shibata E, Morita KI, Kayamori K et al (2021) Detection of novel fusion genes by next-generation sequencing-based targeted RNA sequencing analysis in adenoid cystic carcinoma of head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol 132:426–433 PubMed

Feinberg J, Da Cruz PA, da Silva EM et al (2024) Adenoid cystic carcinoma of the Bartholin’s gland is underpinned by MYB- and MYBL1- rearrangements. Gynecol Oncol 185:58–67 PubMed PMC

Drier Y, Cotton MJ, Williamson KE et al (2016) An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet 48:265–272 PubMed PMC

Mitani Y, Rao PH, Futreal PA et al (2011) Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. Clin Cancer Res 17:7003–7014 PubMed PMC

Tang YF, An PG, Gu BX et al (2023) Transcriptomic insights into adenoid cystic carcinoma via RNA sequencing. Front Genet 14:1144945 PubMed PMC

Baneckova M, Vanecek T, Laco J, et al. 1243. Report of 20 cases of seromucinous hamartomas and respiratory epithelial adenomatoid hamartomas with dysplastic and malignant features.

Bradova M, Agaimy A, Laco J, et al. 1039. A subset of adenoid cystic carcinomas is accompanied by seromucinous hamartoma and/or atypical sinonasal glands arising from seromucinous hamartoma.

Michal M, Skalova A, Hyrcza M, et al. Nasal and sinonasal tumors formed by atypical adenomatous lesions arising in respiratory epithelial adenomatoid hamartoma/seromucinous hamartoma. PubMed

Ozolek JA, Hunt JL (2006) Tumor suppressor gene alterations in respiratory epithelial adenomatoid hamartoma (REAH): comparison to sinonasal adenocarcinoma and inflamed sinonasal mucosa. Am J Surg Pathol 30:1576–1580 PubMed

Jo VY, Mills SE, Cathro HP et al (2009) Low-grade sinonasal adenocarcinomas: the association with and distinction from respiratory epithelial adenomatoid hamartomas and other glandular lesions. Am J Surg Pathol 33:401–408 PubMed

Ambrosini-Spaltro A, Morandi L, Spagnolo DV et al (2010) Nasal seromucinous hamartoma (microglandular adenosis of the nose): a morphological and molecular study of five cases. Virchows Arch 457:727–734 PubMed

Baneckova M, Michal M, Laco J et al (2020) Immunohistochemical and genetic analysis of respiratory epithelial adenomatoid hamartomas and seromucinous hamartomas: are they precursor lesions to sinonasal low-grade tubulopapillary adenocarcinomas? Hum Pathol 97:94–102 PubMed

Rooper LM, Thompson LDR, Gagan J, et al. Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity. PubMed

Dantas AN, Morais EF, Macedo RA et al (2015) Clinicopathological characteristics and perineural invasion in adenoid cystic carcinoma: a systematic review. Braz J Otorhinolaryngol 81:329–335 PubMed PMC

International H, Neck Scientific G (2016) Cervical lymph node metastasis in adenoid cystic carcinoma of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal: a collective international review. J Laryngol Otol 130:1093–1097 PubMed PMC

Ho AS, Ochoa A, Jayakumaran G et al (2019) Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma. J Clin Invest 129:4276–4289 PubMed PMC

Volpi L, Bignami M, Lepera D et al (2019) Endoscopic endonasal resection of adenoid cystic carcinoma of the sinonasal tract and skull base. Laryngoscope 129:1071–1077 PubMed

Haerle SK, Gullane PJ, Witterick IJ et al (2013) Sinonasal carcinomas: epidemiology, pathology, and management. Neurosurg Clin N Am 24:39–49 PubMed

Pommier P, Liebsch NJ, Deschler DG et al (2006) Proton beam radiation therapy for skull base adenoid cystic carcinoma. Arch Otolaryngol Head Neck Surg 132:1242–1249 PubMed

Mauthe T, Holzmann D, Soyka MB et al (2023) Overall and disease-specific survival of sinonasal adenoid cystic carcinoma: a systematic review and meta-analysis. Rhinology 61:508–518 PubMed

Cavalieri S, Mariani L, Vander Poorten V et al (2020) Prognostic nomogram in patients with metastatic adenoid cystic carcinoma of the salivary glands. Eur J Cancer 136:35–42 PubMed

Ali S, Palmer FL, Katabi N et al (2017) Long-term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation. Laryngoscope 127:2265–2269 PubMed PMC

Landrum MJ, Lee JM, Benson M et al (2018) ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res 46:D1062–D1067 PubMed PMC

Steiner P, Andreasen S, Grossmann P et al (2018) Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands. Virchows Arch 473:471–480 PubMed

Michal M, Berry RS, Rubin BP et al (2018) EWSR1-SMAD3-rearranged fibroblastic tumor: an emerging entity in an increasingly more complex group of fibroblastic/myofibroblastic neoplasms. Am J Surg Pathol 42:1325–1333 PubMed

van Dongen JJ, Langerak AW, Bruggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317 PubMed

Kazakov DV, Nemcova J, Mikyskova I et al (2007) Human papillomavirus in lesions of anogenital mammary-like glands. Int J Gynecol Pathol 26:475–480 PubMed

Hagmar B, Johansson B, Kalantari M et al (1992) The incidence of HPV in a Swedish series of invasive cervical carcinoma. Med Oncol Tumor Pharmacother 9:113–117 PubMed

Skalova A, Klubickova N, Bradova M, et al. Discovery of Novel TULP4/ACTN4/EWSR1/ACTB::MYB and ESRRG::DNM3 fusions expands molecular landscape of adenoid cystic carcinoma beyond fusions between MYB/MYBL1 and NFIB genes. PubMed PMC

Atallah S, Casiraghi O, Fakhry N et al (2020) A prospective multicentre REFCOR study of 470 cases of head and neck adenoid cystic carcinoma: epidemiology and prognostic factors. Eur J Cancer 130:241–249 PubMed

Rhee CS, Won TB, Lee CH et al (2006) Adenoid cystic carcinoma of the sinonasal tract: treatment results. Laryngoscope 116:982–986 PubMed

Lupinetti AD, Roberts DB, Williams MD et al (2007) Sinonasal adenoid cystic carcinoma: the M. D Anderson Cancer Center experience Cancer 110:2726–2731 PubMed

Unsal AA, Chung SY, Zhou AH et al (2017) Sinonasal adenoid cystic carcinoma: a population-based analysis of 694 cases. Int Forum Allergy Rhinol 7:312–320 PubMed

Szanto PA, Luna MA, Tortoledo ME et al (1984) Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 54:1062–1069 PubMed

Perzin KH, Gullane P, Clairmont AC (1978) Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer 42:265–282 PubMed

Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. PubMed

van Weert S, van der Waal I, Witte BI et al (2015) Histopathological grading of adenoid cystic carcinoma of the head and neck: analysis of currently used grading systems and proposal for a simplified grading scheme. Oral Oncol 51:71–76 PubMed

Gnepp DR, Heffner DK (1989) Mucosal origin of sinonasal tract adenomatous neoplasms. Mod Pathol 2:365–371 PubMed

Hunt JL, Yim JH, Carty SE (2006) Fractional allelic loss of tumor suppressor genes identifies malignancy and predicts clinical outcome in follicular thyroid tumors. Thyroid 16:643–649 PubMed

Hunt JL, Carty SE, Yim JH et al (2005) Allelic loss in parathyroid neoplasia can help characterize malignancy. Am J Surg Pathol 29:1049–1055 PubMed

Domfeh AB, Fichera M, Hunt JL (2006) Allelic loss of 3 different tumor suppressor gene loci in benign and malignant endothelial tumors of the head and neck. Arch Pathol Lab Med 130:1184–1187 PubMed

Bradova M, Costes-Martineau V, Laco J, et al. Sinonasal adenosquamous carcinomas arising in seromucinous hamartoma or respiratory epithelial adenomatoid hamartoma with atypical features: report of five detailed clinicopathological and molecular characterisation of rare entity. PubMed PMC

Kwok ALM, Chan JKC, Tang AHN et al (2023) Adenofibromatous solitary fibrous tumor: an unusual morphologic variant occurring in the sinonasal tract. Head Neck Pathol 17:165–171 PubMed PMC

Stephens PJ, Davies HR, Mitani Y et al (2013) Whole exome sequencing of adenoid cystic carcinoma. J Clin Invest 123:2965–2968 PubMed PMC

Ho AS, Kannan K, Roy DM et al (2013) The mutational landscape of adenoid cystic carcinoma. Nat Genet 45:791–798 PubMed PMC

Zboray K, Mohrherr J, Stiedl P et al (2018) AKT3 drives adenoid cystic carcinoma development in salivary glands. Cancer Med 7:445–453 PubMed PMC