Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition.

Intestinal-type adenocarcinoma (ITAC) of sinonasal tract is a rare malignant tumor with strong morphological, immunophenotypical, and molecular similarities to colorectal adenocarcinoma (CRC). Tumor budding (TB) is a well-established adverse prognostic marker in CRC and some head and neck tumors, with features of epithelial-mesenchymal transition (EMT). The aim of this study was to assess TB in ITAC and to evaluate its possible association with EMT markers in this setting. We selected 32 surgically resected specimens of non-mucinous/non-signet ring ITAC and evaluated them for TB according to the international recommendations developed for CRC. The expression of the EMT markers E-cadherin, ZEB1, ZEB2, SLUG, and SNAIL was evaluated by immunohistochemistry (IHC). Results were stratified using clinical and follow-up data (2/32 patients had metastatic disease and 4/32 died of disease). We observed TB in 13/32 (40.6%) ITAC cases including the 7 patients with relapse (p = 0.0005) and the 4 patients dead of disease (p = 0.02). Lymphovascular invasion was associated with TB (p = 0.008). Absence of TB was associated with low ZEB2 expression (p = 0.003). No other association with EMT markers emerged. Occupational exposure to wood and leather dust was not related to the presence of TB. TB interobserver concordance was substantial (proportion of agreement = 87%; Cohen's kappa = 0.73). This work suggests that TB is associated with a worse prognosis in ITAC, but our findings do not seem to support the involvement of EMT in this specific setting. Further larger studies are needed to address this point.

HER2 status in sinonasal intestinal-type adenocarcinoma.

Given that the prognosis of patients with sinonasal intestinal-type adenocarcinoma (ITAC) has not significantly changed recently, there is a desire for new therapeutic approaches to improve clinical management. HER2-targeted therapy has remarkably improved the overall survival of patients with HER2 amplified tumors. To date, HER2 assessment has produced contradictory results in ITAC. The aim of this study was to assess HER2 status at both protein and DNA levels in a large series of ITAC. HER2 status was assessed by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in forty-three patients that underwent surgical resection for ITAC at the Otorhinolaryngology Section, Padua University Hospital, between 2007 and 2016. IHC was evaluated using the four-tier score developed for gastroesophageal cancer. As for IHC, 83.7% (36/43) of ITAC were scored 0, 14% (6/43) 1+, and 2.3% (1/43) 2+. No HER2 amplification was detected by CISH. The present is the largest study of sinonasal ITAC tested with both IHC and CISH confirmation for HER2 status. No HER2 overexpression/amplification was detected. Contrary to previous studies, our findings seem to rule out any oncogenetic role of HER2 in ITAC pathogenesis.

Malignant Versus Benign Tumors of the Sinonasal Cavity: A Case-Control Study on Occupational Etiology.

Case-control studies on malignant sinonasal tumors and occupational risk factors are generally weakened by non-occupational confounders and the selection of suitable controls. This study aimed to confirm the association between sinonasal malignant tumors and patients' occupations with consideration for sinonasal inverted papillomas (SNIPs) as a control group. Thirty-two patients affected by adenocarcinoma (ADC) and 21 non-adenocarcinoma epithelial tumors (NAETs) were compared to 65 patients diagnosed with SNIPs. All patients were recruited in the same clinical setting between 2004 and 2016. A questionnaire was used to collect information on non-occupational factors (age, sex, smoking, allergies, and chronic sinusitis) and occupations (wood- and leather-related occupations, textile industry, metal working). Odds ratios (OR) with 95% confidence intervals (CI) associated with selected occupations were obtained by a multinomial and exact logistic regression. Between the three groups of patients, SNIP patients were significantly younger than ADC patients (p = 0.026). The risk of NAET increased in woodworkers (OR = 9.42; CI = 1.94⁻45.6) and metal workers (OR = 5.65; CI = 1.12⁻28.6). The risk of ADC increased in wood (OR = 86.3; CI = 15.2⁻488) and leather workers (OR = 119.4; CI = 11.3⁻1258). On the exact logistic regression, the OR associated to the textile industry was 9.32 (95%CI = 1.10⁻Inf) for ADC, and 7.21 (95%CI = 0.55⁻Inf) for NAET. Comparing sinonasal malignant tumors with controls recruited from the same clinical setting allowed demonstrating an increased risk associated with multiple occupations. Well-matched samples of cases and controls reduced the confounding bias and increased the strength of the association.

Clinical features and management of antrochoanal polyps in children: Cues from a clinical series of 58 patients.

OBJECTIVE: To review the clinical features of pediatric patients affected by antrochoanal polyps (ACPs) and surgically treated at three University settings. METHODS: Retrospective study. The present research includes the clinical data of subjects affected by ACPs, aged <18 years and referred to three ENT Departments, between January 1st 2003 and September 30th 2016. All patients underwent nasal endoscopy and sinonasal imaging; all subjects have been treated surgically. RESULTS: Fifty-eight patients underwent functional endoscopic sinus surgery (FESS) for ACPs removal, under general anesthesia. There were no major intraoperative complications. Recurrence occurred in 12 cases (20.5%). CONCLUSIONS: FESS was the first-choice treatment for APCs in the present series; our recurrence rate was similar to that of other reports available in literature. Recurrences of ACPs in children still represent a clinical challenge; it is likely that an improved comprehension of ACPs biology could help in better understanding the pathophysiology of this disease.

A case-case study on sinonasal cancer prevention: effect from dust reduction in woodworking and risk of mastic/solvents in shoemaking.

BACKGROUND AND AIMS: Sinonasal cancers (SNCs) are rare neoplasms, accounting for about 3 % of head and neck cancers, with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) as the most common subtypes. ADCs present strong associations with occupational wood dust exposure. Preventive measures have progressively reduced wood dust concentrations in workplaces but no study has evaluated the effectiveness of such interventions. Few studies indicate associations between ADC and exposure to solvents, which is common in the shoe industry, but this hypothesis still needs confirmation. METHODS: In a case-case study, we contrasted 32 ADCs against 21 Non-Adenocarcinoma Epithelial Tumors (NAETs) - all recruited from the same clinical setting (Padua's University Hospital; period 2004-2015) - using questionnaires and clinical records to collect information on potential predictors. Non-occupational factors were age, sex, smoking, allergy and chronic sinusitis. Occupational factors were intensity and frequency of wood dust exposure, protection from wood dust, type of wood (in woodworking); frequency of exposure to leather dust or mastic/solvent (in shoemaking). Odds-ratio (OR), 95 % confidence interval (95 % CI) and two-tail p-values were obtained through stepwise backward logistic regression for each industry, always using as reference patients never employed in either trade and adjusting for non-occupational risk factors. RESULTS: Adjusted OR was 22.5 (95 % CI = 3.50-144; p = 0.001) and 9.37 (95 % CI = 1.29-67.6; p = 0.026), respectively, in patients with low or high degree of protection against wood dust. In the shoe industry, adjusted OR was 1 and 18.8 (95 % CI = 1.29-174; p = 0.030), respectively, in patients with low or high exposure to only mastic/solvent; and 1 and 22.5 (95 % CI = 2.07-244; p = 0.011), respectively, in patients with low or high exposure to only leather dust. DISCUSSION AND CONCLUSIONS: The questionnaire used was able to estimate with simple algorithms past exposures in wood and footwear industries. The case-case design considerably increased the validity of this small study. Results in this study were always consistent with the extant literature; this could support reliability of novel findings. In woodworking, respiratory protective equipment and local exhaust ventilation reduced the risk of occupational SNC; in footwear manufacture, where preventive interventions were seldom adopted, SNC risk was significantly greater for high exposure from mastic/solvent and leather dust.