Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISPassociated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.Additional Supporting Information may be found in the online version of this article. Conflict of interest: The authors declare no conflict of interest.

Objectives Adenoid cystic carcinoma (ACC) is a locally aggressive salivary gland malignancy prone to perineural invasion and local recurrences. In the literature, few data exist to guide treatment when this tumor involves the paranasal sinuses and skull base. We report our experience in the management of sinonasal adenoid cystic carcinoma through an endoscopic endonasal approach. Methods Retrospective analysis of patients affected by sinonasal ACC treated through an endoscopic endonasal approach from 1997 to 2015, managed at the Universities of Varese and Brescia, Italy. Results Thirty‐four patients were included in the analysis. The ethmoid sinus (55.9%), nasal septum (17.7%), maxillary sinus (11.7%), and sphenoid sinus (5.9%) were the primary tumor sites encountered. Twenty patients (58.8%) presented with T3 or T4, without any systemic spreading. Twenty‐nine patients underwent endoscopic transnasal resection, whereas the involvement of the anterior skull base in five cases required a transnasal endoscopic craniectomy. Overall, 20 of 34 (58.8%) patients received some form of adjuvant radiotherapy. The follow‐up ranged from 12 to 202 months (mean of 73.2 months). The 5‐year overall, disease‐specific, and recurrence‐free survival rates were 86.5% ± 7.39%, 86.5% ± 7.39%, and 71.8% ± 8.67%, respectively. Conclusions The endoscopic approach is safe and effective for selected sinonasal ACC, reducing the comorbidities of the external approaches while producing similar oncological results. High T‐stage, grade III histology, positive surgical margins, and perineural infiltration all have an important negative prognostic value. Level of Evidence 4 Laryngoscope, 129:1071–1077, 2019

Background: Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several epigenetic markers have been suggested to support the histopathological classification, predict prognosis, and guide therapeutic decision. Indeed, molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as separate entities. Identification of aberrant DNA methylation levels associated with these specific epigenetic driver genes could be useful for prognostic and therapeutic purpose. Methods: Histopathological review and immunohistochemical study was performed on 53 PDSNCs. Molecular analysis included mutational profile by NGS, Sanger sequencing, and MLPA analyses, and global DNA methylation profile using LINE-1 bisulfite-PCR and pyrosequencing analysis. Results: Nine SWI/SNF complex defective cases and five IDH2 p.Arg172x cases were identified. A significant correlation between INI-1 or IDH2 defects and LINE-1 hypermethylation was observed (p = 0.002 and p = 0.032, respectively), which were associated with a worse prognosis (p = 0.007). Conclusions: Genetic and epigenetic characterization of PDSNCs should be performed to identify distinct prognostic entities, which deserved a tailored clinical treatment.

Owner and Responsible Manager on behalf of the Turkish Otorhinolaryngology Head and Neck Surgery Society / Türk Kulak Burun Boğaz ve Baş Boyun Cerrahisi Derneği adına Sahibi ve Sorumlu Yazı İşleri Müdürü: Özgür YİĞİT •