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Background: Sinonasal inverted papilloma (SIP) is a benign tumour originating from the sinonasal mucosa showing an extensive growth pattern, a high risk of recurrence and a 5–10% risk to malignify. Epstein-Barr virus (EBV) is an oncogenic herpesvirus which infects most individuals via the saliva eliciting a latent infection. Previous studies have been reporting variable data on EBV in SIP, and there is no present appreciation regarding the association between these. Aims/objectives: The aims were to investigate the presence and count of EBV in SIP and map the viral distribution in the epithelium versus the connective tissue. Material and method: Fifty-three SIP patients were identified in the Pathology Department register at the University Hospital of Umeå. The biopsies were analysed with Epstein-Barr Encoded Region (EBER) in situ hybridization. EBER-positive cells were counted in the epithelium and connective tissue. Results: We found EBER-stained cells in 30% of the cases, where 19% of these had an abundance of stained cells, and the rest showed a low count. Conclusions/significance: These findings demonstrate a low EBV count in SIP. EBV is less likely to be a causative agent in the formation of SIP, or its malignant transformation.

BackgroundInverted papilloma (IP) is an unusual type of benign tumor that has high recurrence rates and the potential to transform into squamous cell carcinomas (SCC). The mechanism of the transformation process from IP to IP-SCC is uncertain and there is no consensus regarding the best practice for IP-SCC detection. The goal of this study is to identify the best clinical methods to detect for IP-SCC.MethodsAn evidence-based review was performed using Medline and Ovid to obtain all articles up to October 10th, 2019 pertaining to identification of IP malignant transformation. All manuscripts discussing clinical methods or biomarkers were included.ResultsBased on clinical research studies, convoluted cerebriform pattern and apparent diffusion coefficient values on Magnetic Resonance Imaging (MRI) can help differentiate benign IP from SCC and increased SUVmax on PET/CT is associated with higher probability of malignancy although not as specific. No consensus about the best biomarker for IP-SCC has been reached among researchers and continues to be exploratory.ConclusionEndoscopy with biopsy is the gold standard practice to identify IP-SCC; however, MRI is the preferred imaging modality to recognize malignant transformation in cases where biopsy is difficult. Multiple biomarkers have shown positive results, but no single indicator with clinical significance for monitoring malignant transformation process has been found.

Background Inverted urothelial papilloma (IUP) of the upper urinary tract is an uncommon benign tumour that occasionally presents as a polypoid mass causing urinary obstruction. Histologically, IUP is characterised by a proliferating urothelium arranged in cords and trabeculae, in continuity with overlying intact epithelium, and extending into the lamina propria in a non-invasive, endophytic manner. Cytological atypia is minimal or absent. Top differential diagnoses include urothelial carcinoma with inverted growth pattern and florid ureteritis cystica. Although urothelial carcinomas of the upper urinary tract with prominent inverted growth pattern commonly harbour microsatellite instability, the role of the mutator phenotype pathway in IUP development is still unclear. The aim of this study was to describe two additional cases of IUP of the upper urinary tract, along with an extensive literature review. Case presentation We observed two polypoid tumours originating in the renal pelvis and the distal ureter, respectively. Both patients, a 76-year-old woman and a 56-year-old man, underwent surgery because of the increased likelihood of malignancy. Histology was consistent with IUP and patients are alive and asymptomatic after long-term follow-up (6 years for the renal pelvis lesion and 5 years for the ureter lesion). The tumours retained the expression of the mismatch-repair protein MLH1, MSH2, and PMS2 whereas loss of MSH6 was found in both cases. Conclusions When completely resected, IUP does not require rigorous surveillance protocols, such as those for urothelial carcinoma and exophytic urothelial papilloma. It is therefore important for the surgical pathologist to be aware of this rare entity in order to ensure correct patient management.

Nasal and sinonasal inverted papilloma (IP) are rare benign tumors and have the potential to exhibit malignancy in approximately 10% of cases. This study aimed to analyze the clinical features of IP associated with malignancy. Furthermore, we reviewed our therapeutic strategy and the clinical course of malignant IP.Overall, 70 patients with IP at our institution were retrospectively analyzed from April 2006 to December 2015; of these, six (9%) had associated malignancy. Data was collected on sex, age, presenting symptoms (nasal bleeding, rhinorrhea, facial or cheek pain, and nasal obstruction), bone destruction, and extent of disease on CT and MRI. Categorical data of patients with and without malignancy were compared using the chi-square test. A p value of0.05 was considered statistically significant. Our therapeutic strategy for IP with malignancy, particularly the surgical procedure, i.e., the external incision or the endoscopic nasal approach, varied based on when the carcinoma was detected. In addition, we considered postoperative radiation therapy depending on histological examination.Nasal bleeding (p0.001), pain (p=0.040), bone destruction (p0.001), and extent of disease (p=0.026) on CT and MRI findings were significantly associated with malignancy. Carcinoma was diagnosed preoperatively in two (33%) and postoperatively in four patients (67%). We operated five patients (one case was not treated because of end-stage pancreatic cancer). Two patients underwent endoscopic sinus surgery (ESS) alone, two ESS plus Denker's method, and one ESS plus anterior craniotomy. Three patients underwent surgery only, and two patients received postoperative radiotherapy. The median follow-up period was 69.3 months. One patient died of the disease and the remaining patients are alive without recurrence.For IP patients exhibiting these clinical findings preoperatively, we should suspect complication with malignancy and plan a treatment. Even if postoperative histology does not confirm malignancy, we should ensure careful observation because of metachronous malignant transformation or the possibility to overlook small malignant lesions. Our result suggests that our strategy for malignant IP could be a reasonable option.

Objectives: The aim of this study was to further characterize a newly described neoplasm, low-grade papillary Schneiderian carcinoma, occurring simultaneously in the sinonasal cavity and mastoid. Additionally, the authors review the only 2 similar cases within the literature and describe the common clinical features, radiographic findings, and pathologic characteristics of this exceptionally rare disease process. Methods: Chart review for single patient, review of literature. Results: The patient presented with bilateral nasal obstruction. Computed tomography revealed a left sinonasal mass with skull base hyperostosis, and follow-up magnetic resonance imaging showed a concomitant olfactory groove meningioma. Examination showed a bilateral, completely obstructing sinonasal mass with skip areas, and biopsy confirmed inverted papilloma (human papilloma virus strains 16 and 18 indeterminate). The patient underwent bilateral endoscopic sinus surgery, left medial maxillectomy, and left partial nasopharyngectomy. Given her multifocal disease, she was advised that she would require additional excision, but was lost to follow up. One year later she developed acute left facial paralysis. Magnetic resonance imaging demonstrated an enhancing mass in the left mastoid with enhancement along the Eustachian tube in addition to her known recurrent sinonasal disease. Simultaneous endoscopic sinus surgery and mastoidectomy were performed. Polypoid tissue was removed from the nasopharynx, mesotympanum, epitympanum, and retrofacial air cells. Immunohistochemistry showed that cells stained positive for p63 and dermCK and negative for synaptophysin. Morphologically, cells were bland, without classic stromal invasion, retaining their smooth, cystic, and papillary features, despite their increased depth within the tissue. Upon further review and consultation with an outside pathologist, a diagnosis of low-grade papillary Schneiderian carcinoma was made. The patient was referred for radiation therapy and is disease free at 3-month follow-up, with return of her facial function. Conclusions: This case represents the first report of concurrent low-grade papillary Schneiderian carcinoma of both the nasal cavity and mastoid. It emphasizes the importance of recognizing this new entity through pathologic analysis and suspecting it when the clinical course does not follow an expected pattern.

Background The intranasal endoscopic prelacrimal recess approach (PLRA) access to all aspects of the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct and its use have been reported in the treatment of many maxillary sinus and lateral skull base diseases. Objective To retrospectively assess the effectiveness of a 10-year multicenter follow-up for the resection of inverted papilloma of the maxillary sinus (IPMS) via a PLRA. Methods A total of 71 patients were admitted and underwent IPMS excision via an intranasal endoscopic PLRA from 2003 to 2013. All patients underwent high-resolution computed tomography scanning of the nasal sinus, and some also underwent magnetic resonance imaging examination. Results Based on the Krouse staging system, all 71 patients belong to T3 staging. The PLRA was employed to remove IPMS in 71 patients. The postoperative pathological examination of the excised tissue revealed inverted papilloma, and cancerization was identified in 3 patients. The median follow-up time was 37.3 months (range: 13–134 months). Of the 71 patients, reoccurrence was seen in 5 patients (7.04%); 5 patients (7.04%) experienced numbness of the upper lid and the ala of the nose and 4 (5.63%) experienced mild collapse of the ala of the nose. Conclusions These multicenter follow-up results demonstrated that the PLRA is a safe and effective method for the excision of primary or recurrent IPMS with lower postoperative complications and recurrent rate.

Purpose This study aims to determine the indications and effectiveness of transnasal endoscopic prelacrimal recess approach (PLRA) in patients with maxillary sinus inverted papilloma (IP). Methods We retrospectively analyzed 71 patients treated in our institution for maxillary sinus IP between August 2008 and April 2015. 20 patients underwent endoscopic surgery via PLRA. All the patients who had postoperative follow-up for 3 years were enrolled. Demographic data, surgical technique, location of IP attachment, intra- and postoperative complications, follow-up duration and recurrence were recorded. Results The outpatient follow-up period was 3–10 years after surgery. Recurrence of IP was seen in 6 (8.5%) of 71 patients, including 1 patient in the PLRA group. The recurrence rate was 5% in the PLRA group. Six of 71 patients experienced postoperative complications, but none was observed in the PLRA group. Conclusion Transnasal endoscopic PLRA is a minimally invasive, safe and effective method for maxillary sinus IP. The indication for PLRA is tumor pedicle located on the antero-inferior or infero-lateral wall or at multiple attachment sites of the maxillary sinus.

Optical coherence tomography (OCT) and confocal laser scanning microscopy (CLSM) are light-based imaging techniques that allow for a visualization of microscopic tissue properties in vivo. Our study was to examine whether they allow for differentiation of inverted papilloma (IP) from nasal polyps (NP). Five cases of IP and NP, respectively, were investigated intraoperatively with OCT and CLSM. Biopsies were taken of the investigated area and were analyzed ex vivo with OCT and CLSM and then underwent HE-staining for standard light microscopy. On OCT images, IP showed the characteristic inverted character of the epithelium, that was thicker with a high degree of variability of thickness compared to the thin and homogenous epithelium of NP. In addition, the characteristic stromal edema of NP could be visualized. On CLSM images, the typical epithelial invaginations of IP appeared as crypts, while in NP the highly organized cylindric epithelium could be visualized. In vivo, OCT acquired images of sufficient quality to visualize these characteristics, while CLSM did not. Our study demonstrates that OCT and CLSM can distinguish IP from NP. Further technical development is required to apply the techniques clinically to guide intranasal biopsies or even to make them dispensable.

Background Pure endoscopic surgery (functional endoscopic sinus surgery) has been increasingly replacing external approaches in the management of sinonasal inverted papillomas. Objective To analyze and compare the effectiveness of pure endoscopic procedure with external or combined procedures to paranasal inverted papillomas, including the experience from two institutions in North Greece, over a 20-year period. Methods Systematic literature searches of MEDLINE (1952–2016), EMBASE (1974–2016), and the Cochrane Central Register of Controlled Trials. Review of all English-language studies comparing endoscopic and open techniques. Odds ratios (ORs), risk ratio, 95% confidence intervals (CIs), and tests for heterogeneity were reported. Recurrence rates according to initial tumor stage. Results In total, 2451 patients had been enrolled in the 23 studies, published between 1992 and 2014. All the included articles are graded as level IV evidence. Among the 1526 patients of the endoscopic group, 212 (13.8%) had recurrence, with the mean time of recurrence to range from 14 to 46.6 months. In the external approach group, 111 (18.7%) of the 592 patients had recurrence, with the time of recurrence to range from 7 to 92 months. The recurrence rate in the combined approach group was 12.9%. The occurrence rate of recurrence attributable to the surgical choice was significantly different between endoscopic and external group (OR: 0.61; 95% CI: 0.40–0.92; P = 0.02; 14.9% vs. 18.8% in endoscopic and external group, respectively). Conclusions The present systematic review and meta-analysis indicates that endoscopic approach seems a favorable treatment option of sinonasal inverted papillomas and confirms the global recommendation that is the gold standard in the treatment of such nose lesions, revealing a lower recurrence rate compared to external approaches.

Background Inverted sinonasal (Schneiderian) papilloma (ISP) is a locally aggressive neoplasm often associated with sinonasal squamous cell carcinoma (SNSCC). While the etiology of ISP is not well understood, human papillomavirus (HPV) has been detected in a subset of cases. Our group recently identified activating somatic EGFR mutations in the majority of ISP and ISP-associated SNSCC. However, the relationship between EGFR mutations and HPV infection has not been explored. Patients and methods We evaluated 58 ISP and 22 ISP-associated SNSCC (including 13 patients with matched ISP/SNSCC samples), as well as 14 SNSCC without clinical or pathologic evidence of an associated ISP. Formalin-fixed, paraffin-embedded samples were evaluated for EGFR mutations using Sanger sequencing and for HPV infection using GP5+/GP6+ PCR. HPV subtyping based on the L1 sequence was done for HPV positive cases including temporally distinct tumors for four patients. Clinicopathologic data including progression free survival was also analyzed. Results All ISP and ISP-associated SNSCC demonstrated either an EGFR mutation or HPV infection. HPV and EGFR mutation were mutually exclusive in all cases of ISP-associated SNSCC and all but one ISP; this case was only weakly HPV positive, and analysis of a prior temporally distinct ISP specimen from this patient failed to show HPV infection, suggesting transient infection/incidental colonization. HPV subtypes in ISP and ISP-associated SNSCC were predominantly low-risk, in contrast with SNSCC without ISP association, which showed frequent high-risk HPV. All paired ISP and associated SNSCC samples demonstrated concordant HPV status and EGFR genotypes. ISP progression to SNSCC was significantly associated with the presence of HPV infection and the absence of an EGFR mutation (log-rank = 9.620, P = 0.002). Conclusions Collectively our data show that EGFR mutations and HPV infection represent essential, alternative oncogenic mechanisms in ISP and ISP-associated SNSCC.

Background Sinonasal exophytic papillomas are rare. The multifocal form, florid papillomatosis, has not been yet described in literature. We report on the clinical features and the management of the different forms of exophytic papilloma. Methods A retrospective study was conducted that included all patients with exophytic papilloma treated in our center over the past 12 years. We recorded clinical presentation, treatments, recurrences, pathology (p16 expression and human papillomavirus [HPV] status). Results We included 13 patients with a mean follow-up of 5 years. The main location of exophytic papilloma was the anterior part of the septum. Lesions were multifocal in 3 patients corresponding to florid papillomatosis. The main treatment was surgery. Cases of HPV-11 or HPV-6 were present in all forms of exophytic papilloma (dysplasia in 4 cases). Late recurrences occurred in 3 patients (2 patients with florid papillomatosis) over a period of 3 years. Conclusion Exophytic papilloma has 2 clinical presentations: localized and diffuse. Patients with florid papillomatosis should be monitored closely as recurrence seems to be frequent.

AIMS Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been found frequently in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. METHODS AND RESULTS The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs). TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade NIPUCs, but not in any inverted papilloma. FGFR3 mutations were observed more frequently in PUNLMP and low-grade NIPUC than in inverted papillomas (P = 0.009), whereas the opposite trend was noted for HRAS mutations (P

The development of orbit-eroding mucocele associated with inverted papilloma has been rarely reported., Here, the authors present a case and surgical management of a patient with orbit-eroding mucocele associated with inverted papilloma who declined craniotomy. A combined approach utilizing frontal endoscopic sinus surgery and external sub-brow anterior orbitotomy was used to explore, drain, and excise the mucocele and inverted papilloma. Gelatin sponges soaked in gentamicin were used to cover the exposed dura and to protect the orbital content from the frontal sinus cavity.A fronto-ethmoidal sinus inverted papilloma associated with recurrent orbit-eroding mucocele was excised by combined transnasal endoscopic and external sub-brow anterior orbitotomy approach using stereotactic navigation.

Introduction. The aim of this study was to analyse the occurrence of inverted papillomas of the nose and paranasal sinuses in patients that underwent endoscopic sinus surgery in our department. Material and methods. Between 2006 and 2016, 3,574 patients underwent surgery due to paranasal sinus diseases. Patients were qualified for surgery based on medical history, computed tomography, and laboratory tests. Data were gathered from medical files, and they included age, sex, and histopathological diagnosis. Results. Among 3,574 patients that underwent surgery due to chronic inflammatory changes, on histopathology, inverted papillomas were diagnosed in 80 patients, including 31 women (38.75%) and 49 men (61.25%). Most patients were aged 60-70 years (women, 12.5%; men, 15%) or 50-60 years (women, 5%; men, 21.25%). Between 2006 and 2016, the number of surgeries ranged from 264 (7.38%) in 2013 to 355 (9.93%) in 2016, and the number of inverted papillomas ranged from 4 in 2007 and 2015 (1.23%) to 12 in 2014 (3.87%). Over the last 4 years of the study period, the incidence of inverted papillomas increased. Conclusions. Among 3,574 patients operated on due to chronic inflammatory changes, on histopathology, inverted papillomas were diagnosed in 80 cases (2.23%); thus, all patients qualified for endoscopic surgery due to inflammatory or hypertrophic changes should undergo rhino-fiberoscopy. Recurrence of inverted papillomas was observed in 17.50%, typically in patients with nasal polyps that co-occurred with inverted papillomas. We regard rhino-fiberoscopy as the most valuable method for detecting tumour recurrence in patients after surgery for inverted papillomas.

Basaloid squamous cell carcinoma (BSCC) is a histologically distinctive variant of squamous cell carcinoma comprising basal cell carcinoma and squamous cell carcinoma. BSCC is aggressive and shows a poor prognosis because of frequent lymph node invasion and distant metastases. BSCC preferentially occurs in the cervix, thymus, and esophagus and is uncommonly found in the head and neck region. BSCC in the nasal cavity or paranasal sinus is particularly rare. Inverted papilloma is an uncommon, benign tumor with a propensity to be associated with malignancy; however, BSCC arising in an inverted papilloma has never been reported. Here we report a case of a 56-year-old woman with BSCC arising in an inverted papilloma in the nasal cavity. The woman was referred to our hospital for epistaxis, nasal congestion, and dysphagia. A tumor was observed to completely occupy the left nasal cavity. The biopsy specimen was histologically diagnosed as papilloma. Computed tomography demonstrated a tumor with heterogeneous contrast effect occupying the left nasal cavity; however, extra-nasal tract extension was not observed. We performed endoscopic excision of the tumor. Microscopic findings confirmed the diagnosis of BSCC arising from an inverted papilloma. No tumor recurrence has been observed for 13 months after surgery.

Introduction Inverted papillomas are notorious for recurrence. The surgical cause attributed to recurrence is failure to achieve good surgical exposure and inadequate clearance of disease. Pre-operative prediction about the site of origin by CT Scan may contribute to a better surgical outcome. This study was undertaken to assess if focal hyperostosis on pre-operative CT scan can be considered to be a predictor of the site of tumour origin and correlate with endoscopic finding of the site of origin. Materials and Method A prospective descriptive study was carried out between Jan 2014 and May 2016. Fifteen patients of histopathologically proven inverted papilloma that reported during this time period were evaluated using contrast enhanced CT Scan and subsequently underwent endoscopic excision of tumour identifying the tumour origin. Assessment of age, gender, symptoms, pre-operative staging, location of the tumour origin on CT Scan and surgical correlation of origin was done. Post-operative follow-up was done at 1 month, 3 months and 6 monthly thereafter. Results Six (40%) were classified as Krouse II and nine (60%) were classified as Krouse III. 12 (80%) arising from maxillary sinus, 02 (13.3%) arising from maxillary sinus and anterior ethmoids and 01 (6.7%) from sphenoid. Thirteen (86.7%) cases CT scan could predict the tumour origin which was confirmed during surgery. All cases managed by endoscopic technique with no recurrence or co-existence of malignancy. Discussion Focal hyperostosis in the walls of paranasal sinus is seen to be associated with IP tumour origin, the cause of which is not fully understood. It is hypothesized that tumour induced inflammation at the site of origin leads to bone remodeling and increased bone deposition with vascularity at the site of attachment. Conclusion CT scan is a good predictor of tumour origin and a conservative endoscopic approach can be planned accordingly for complete clearance of disease.

Objectives:Sinonasal inverted papillomas (SIP) present a potential for recurrence years after the surgery, but most studies report short-term follow-up, and risk factors for recurrence are still debated. Furthermore, several classifications are described, and no consensus exists regarding which one should be used. The aims of this study were to report our long-term results, investigate for potential risk factors for recurrence, and compare the existing 8 staging systems.Methods:Over a 28-year period, 110 patients with a diagnosis of SIP were enrolled. The median follow-up time was 55.6 months.Results:In multivariate Cox regression modeling, history of previous surgery was the only variable associated with recurrence (hazard ratio = 4.91, 95% CI, 1.80-13.39). Recurrences occurred up to 60 months after the surgery. Among the 8 staging systems, none proved to be associated with recurrence.Conclusion:The only factor associated with recurrence of SIP was prior surgery, probably corresponding to an incomplete initial resection. Due to late recurrences, an extended follow-up of at least 5 years is mandatory. In the absence of a classification predicting prognosis, Krouse’s staging system should be used to homogenize studies’ report since it is the most widely used.

BACKGROUND AND PURPOSE: Because sinonasal inverted papilloma can harbor squamous cell carcinoma, differentiating these tumors is relevant. The objectives of this study were to determine whether MR imaging–based texture analysis can accurately classify cases of noncoexistent squamous cell carcinoma and inverted papilloma and to compare this classification performance with neuroradiologists9 review. MATERIALS AND METHODS: Adult patients who had inverted papilloma or squamous cell carcinoma resected were eligible (coexistent inverted papilloma and squamous cell carcinoma were excluded). Inclusion required tumor size of >1.5 cm and preoperative MR imaging with axial T1, axial T2, and axial T1 postcontrast sequences. Five well-established texture analysis algorithms were applied to an ROI from the largest tumor cross-section. For a training dataset, machine-learning algorithms were used to identify the most accurate model, and performance was also evaluated in a validation dataset. On the basis of 3 separate blinded reviews of the ROI, isolated tumor, and entire images, 2 neuroradiologists predicted tumor type in consensus. RESULTS: The inverted papilloma (n = 24) and squamous cell carcinoma (n = 22) cohorts were matched for age and sex, while squamous cell carcinoma tumor volume was larger (P = .001). The best classification model achieved similar accuracies for training (17 squamous cell carcinomas, 16 inverted papillomas) and validation (7 squamous cell carcinomas, 6 inverted papillomas) datasets of 90.9% and 84.6%, respectively (P = .537). For the combined training and validation cohorts, the machine-learning accuracy (89.1%) was better than that of the neuroradiologists9 ROI review (56.5%, P = .0004) but not significantly different from the neuroradiologists9 review of the tumors (73.9%, P = .060) or entire images (87.0%, P = .748). CONCLUSIONS: MR imaging–based texture analysis has the potential to differentiate squamous cell carcinoma from inverted papilloma and may, in the future, provide incremental information to the neuroradiologist.

BACKGROUND Extended endoscopic maxillectomy (Sturmann-Canfield procedure) allows full visualization of the maxillary sinus by sectioning the lacrimal duct and removing the medial part of the anterior maxillary wall. The aim of this study is to evaluate the morbidity of Sturmann-Canfield procedure in patients treated for inverted papilloma. METHODOLOGY The clinical records of all patients treated with a Sturmann-Canfield procedure for inverted papilloma from October 2000 to September 2015 at two teaching hospitals were reviewed. All patients were evaluated by nasal endoscopy and lacrimal system patency was assessed. Pre-maxillary cutaneous sensitivity was tested with a Semmes-Weinstein aesthesiometer and thermic stimulation. The SNOT-22 questionnaire was administered. Patients were also asked to report any other post-surgical complaints. RESULTS Fifty-nine patients were identified. Mean follow-up after surgery was 66.3 months. Mean SNOT-22 score was 5.94 (range 0-20); the majority of patients (86%) had a SNOT-22 symptom score of 3 or lower. Mucocoele occurred in 3 (5%) cases. Lacrimal pathway obstruction was observed in 7 (12%) patients. Fourteen (24%) patients complained of paraesthesia in the malar area; hypoesthesia was present in only 5 (8%) cases. Hypoesthesia in the region innervated by the anterior superior alveolar nerve was detected in 17 (29%) patients. One patient reported a slight depression of paralateronasal soft tissues. CONCLUSIONS Although nasal function outcomes and the results from SNOT-22 questionnaires were favourable, a high rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention, including the possibility of negative aesthetic sequelae, should be discussed during preoperative counselling.

Introduction and objectives Endoscopic sinonasal surgery is the procedure of choice in the treatment of chronic rhinosinusitis and sinonasal polyposis refractory to medical treatment, with high rates of success (76%–97.5%). However, 2.5%–24% of those patients will require revision surgery (RESS). In this study, we present the clinical, anatomical, radiological and histological features of patients receiving RESS in our centre during a 3-year period. Methods A retrospective review of clinical, anatomical, radiological and histopathological data of patients receiving revision endoscopic sinonasal surgery between 2012 and 2014 was carried out. Results From 299 surgery procedures performed, 27 (9%) were revision surgeries. The mean patient age was 46 years, with a male/female ratio of 1.4/1. The most frequent preoperative and postoperative diagnosis was chronic polypoid rhinosinusitis. The mean time since the previous surgery was 6.1 years, with 11.9 months of mean follow-up since that surgery. Stenotic antrostomy was found during revision in 81.5% of the patients and incomplete anterior ethmoidectomy and persistent uncinate process, in 59.3%. In radiology, 70.4% of patients had persistent anterior ethmoidal cells. Antrostomy or widening of antrostomy was performed in 96.3% of cases and anterior ethmoidectomy or completion of it was performed in 66.7%. Conclusions Polyps, stenotic antrostomy and incomplete ethmoidectomy were the most frequent causes of revision surgery, in concordance with the procedures performed. The patients had long periods of time without follow-up between surgeries. Further investigation is necessary to generate measures to reduce the number of revision surgeries.

To investigate the key imaging points in distinguishing ossifying inverted papilloma (IP) from polyps.The native computed tomography (CT), conventional and enhanced MRI manifestations of 20 ossifying IPs and eight polyps, which were confirmed histopathologically, were retrospectively evaluated by two doctors majoring in head and neck imaging.A significant difference was detected between the two entities for the involved sites (p0.05). Although two lesions had similar CT findings, the MRI features differed significantly (p0.05). Twenty ossifying IPs demonstrated heterogeneously isointense with moderate gadolinium enhancement, and a convoluted "cerebriform" configuration. Seven ossifying polyps revealed low T1 and high T2 signal, with marginal enhancement, and one showed isointense with moderate enhancement. The ossification appeared as oval or striped bone-like high attenuation, which consisted of peripheral hyperattenuating cortical bone and central fat-like attenuation of the medullary cavity. The corresponding MRI findings of the ossifying regions were peripherally low signal and centrally high signal on both T1- and T2-weighted images. The occurrence of two key MRI features of cystic appearance and the "cerebriform" sign were significantly different between two entities (p0.05).CT can better detect intralesional ossification, but MRI is the optimal imaging technique for discriminating between two disease entities.

Background Sinonasal inverted papilloma is a locally aggressive tumor arising from the Schneiderian membrane which lines the nasal cavity and paranasal sinuses. Aggressive surgical approaches, such as lateral rhinotomy, were used until recently for complete removal of the inverted papilloma. Currently, endoscopic resection is the gold standard in the treatment of inverted papilloma. However, there are situations that justify an open approach. For example there are studies that report a higher postoperative recurrence rate after endonasal endoscopic resection, particularly in the treatment of recurrent diseases. While endoscopic resection performed by an experienced surgeon is definitely a minimally invasive therapy, an open approach is not necessarily associated with functional and aesthetic disadvantages. This case report describes the treatment of inverted papilloma by an open approach. This has been described before but the new gold standard of endoscopic resection has to be taken into account before any treatment decision is made nowadays. Case presentation Contrast-enhanced magnetic resonance imaging of the head and neck area was indicated in a 72-year-old white German man who presented with suspected squamous cell carcinoma of his lower lip. Magnetic resonance imaging additionally revealed a 3×2 cm2 polycyclic arranged mucosal thickening with cystic and solid contrast affine shares at the antral laterocaudal area of his right maxillary sinus, extending from his right lateral nasal wall to his maxillary sinus floor. He received antral polypectomy with medial maxillectomy via a unilateral LeFort I osteotomy approach. His pterygoid plate was preserved. A histological examination demonstrated a tumor composed of hyperplastic squamous epithelium protruding into the stroma (surface epithelial cells grew downward into the underlying supportive tissue), thus producing a grossly convoluted cerebriform appearance. Two weeks later, the patient regained a well-formed maxilla without any restrictions. He has remained disease-free for 25 months following the surgery and surveillance was continued in our tumor clinic. Conclusions Endoscopic resection of an inverted papilloma continues to be the gold standard. However, some cases require a radical approach. This does not necessarily increase patient morbidity.

An inverted papilloma is a benign neoplasm that occurs exclusively in the sinonasal cavity; an inverted papilloma involving the mastoid cavity is extremely rare. We present the case of a patient with an inverted papilloma of the mastoid cavity secondary to cholesteatoma surgery. No case that occurred after acquired cholesteatoma has been reported in literature. A 39-year-old female who was diagnosed with cholesteatoma was treated with a modified radical mastoidectomy in 1988. After recurrence, the patient underwent a canal wall down mastoidectomy in 2006. Four years later, the patient complained of right ear fullness; an examination determined that the right ear canal wall was nearly obliterated by a soft tissue mass. Surgery determined that a papilloma-like mass filled the mastoid cavity. The tumor was surgically resected by revision canal wall down mastoidectomy with canaloplasty. Histologically, it was determined to be an inverted papilloma. There has been no evidence of recurrence to date.

Inverted papillomas are tumors of the sinonasal tract with a propensity to recur. Raman spectroscopy can potentially identify inverted papillomas from other tissue based on biochemical signatures. A pilot study comparing Raman spectroscopy to histopathology for 3 types of sinonasal tissue was performed. Spectral data of biopsies from patients with normal sinonasal mucosa, chronic rhinosinusitis, and inverted papillomas are compared to histopathology using principal component analysis and linear discriminant analysis after data preprocessing. A total of 18 normal, 15 chronic rhinosinusitis, and 18 inverted papilloma specimens were evaluated. The model distinguished normal sinonasal mucosa, chronic rhinosinusitis, and inverted papilloma tissue with an overall accuracy of 90.2% (95% confidence interval, 0.86-0.94). In conclusion, Raman spectroscopy can distinguish inverted papilloma, normal sinonasal mucosa, and chronically rhinosinusitis tissue with acceptable accuracy.

Purpose Inverted papilloma (IP) is a tumor usually arising from sinonasal cavities, with tendency for recurrence and possible malignant transformation. Along with endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) play a crucial role in defining preoperative staging, tumor origin, and possible differential diagnosis, with significant repercussions on therapeutic planning. However, at present no consensus has been reached concerning IP diagnostic workup. Aim of this study is to assess CT and MRI sensitivity and specificity in identifying IP imaging hallmarks, evaluating their global diagnostic accuracy in order to define a novel diagnostic flowchart. Methods We retrospectively analyzed multimodal imaging of patients with histologically confirmed IP and mimics. Two neuroradiologists in consensus retrospectively rated the presence of typical imaging features of IP, both on CT and MRI scans. Sensitivity, specificity and diagnostic accuracy were assessed for both the techniques. Final results were expressed as ROC curves and relative areas under the curve (AUC). Results The AUC considering CT parameters were 0.42, whereas the AUC considering MRI parameters were 0.54. Combining the 2 techniques and limiting the evaluation to the most distinctive features such as focal hyperostosis and CCP, the AUC was 0.79. Conclusion MRI can provide better tissue characterization and higher diagnostic accuracy in case of suspected IP, whereas CT is more useful in determining bony involvement. Here we propose a possible diagnostic flowchart for IP, based on the assumption that the combination of the imaging techniques allows to optimize the clinical assessment and the subsequent therapeutic planning.

Background The technique for transnasal endoscopic resection of inverted papilloma (IP) has evolved considerably during the last 20 years. The aim of the present study is to retrospectively analyze a single tertiary center series, with special emphasis on assessing the value of an "insertion-driven" technique on local control. Methods Patients undergoing endoscopic resection for IP at the University of Brescia during the period 1991 to 2015 were enrolled. Site of origin and extension of IPs were assessed, together with presence of dysplasia and carcinoma in situ. Patients were divided in 3 cohorts: (1) historical cohort (treated before 2008), (2) contemporary "centripetal" cohort (treated with a traditional technique after 2008), and (3) contemporary "insertion-driven" cohort (treated with insertion-driven resection). Groups were compared considering outcomes and complications. Results The series included 210 patients. Mean follow-up was 77.8 months. Thirty-eight (18.1%) patients showed precancerous changes. Maxillary involvement (p = 0.021) and presence of precancerous changes (p = 0.013) were significantly associated with a higher risk of recurrence. Five-year local control rate before and after 2008 was 95.1% and 90.5%, respectively. The insertion-driven cohort was associated with lower disease control when IPs involved the maxillary sinus. The rate of complications was 11.9%. The insertion-driven cohort was associated with a lower rate of major complications (p = 0.098). Conclusion Preoperative evidence of precancerous changes and/or involvement of maxillary sinus should prompt the surgeon to address the disease more aggressively (centripetal resection). Preoperative imaging and biopsy with abundant material may optimize the chance to stratify patients eligible for less or more conservative approaches.

BACKGROUND Inverted papilloma (IP) is a locally destructive benign tumour of the sinonasal mucosa with a tendency for malignant transformation. Stathmin and epidermal growth factor receptor (EGFR) are important markers in cancer prognosis. Here we investigate if expression of stathmin and EGFR correlate to dysplasia, recurrence and HPV in IP. METHODS 98 patients with IP diagnosed 2000-2010 were analyzed for stathmin and EGFR by immunohistochemistry (IHC) and HPV by polymerase chain reaction assay (PCR). RESULTS All IPs expressed stathmin while its expression was absent or weak in normal mucosa. Dysplasia was present in 26,7% of IPs with high stathmin expression while only 7.4% of IPs with low stathmin expression showed dysplasia. Stathmin positive IPs showed a trend towards earlier recurrences. 57.1% of IP expressed EGFR but no significant association was seen between EGFR-positivity and recurrence or dysplasia. EGFR was expressed by 91.7% of the HPV-positive IPs compared to 52,3% of the HPV negative IPs. CONCLUSIONS EGFR expression is significantly higher in HPV positive IP. Stathmin is expressed by all IP tumour cells. Stathmin was also associated with dysplasia and a trend towards a correlation between stathmin positivity and recurrence was found. Stathmin and EGFR might therefore be considered therapeutic targets.

Sinonasal inverted papilloma (IP) is a typically benign sinonasal tumor with a tendency to recur and the potential for malignant transformation. Varying degrees of dysplasia may be present, of which carcinoma in situ (CIS) is most advanced. We hereby describe the biological and clinical behavior of IP with CIS (IPwCIS).Retrospective cohort.Tertiary academic referral center.Patients who underwent surgical resection for IP between 2002 and 2017. Pertinent clinical data were obtained, and all IPwCIS cases were histologically confirmed.In total, 37 of 215 cases (17.2%) were identified with IPwCIS. Mean age was 57 years and 86.5% of patients were male. Median follow-up was 82 months, and the recurrence rate was 27%. The maxillary sinus was the most common primary site (37.8%) and 14 tumors (37.8%) demonstrated multifocal attachment, which was associated with recurrence (odds ratio [OR], 9.7; 95% confidence interval [CI], 1.4-112.8;IPwCIS represents the most severe degree of dysplasia prior to malignant transformation and is associated with higher recurrence rate and multifocal involvement but low rate of conversion to invasive carcinoma. The need for adjuvant therapy remains controversial, and further research into the etiology of the disease is warranted.

Background The survival difference between de-novo sinonasal squamous cell carcinoma (DN-SNSCC) and SCC arising from inverted papillomas (IPs) is unclear. The purpose of this study was to compare the outcomes between DN-SNSCC and IP-transformed SNSCC (IP-SNSCC) patients. Methods In this retrospective review, we compared IP-SNSCC and DN-SNSCC cases from the Eye and ENT Hospital of Fudan University from 2010 to 2017. A total of 162 patients (39 IP-SNSCC and 123 DN-SNSCC) were included in our study. Demographics, tumor characteristics, treatment, and clinical outcomes were analyzed. Results The median follow-up time in all cohorts was 56 (range, 5-109) months. There was no difference in age, sex, smoking history, alcohol consumption, tumor primary site, or disease stage between the IP-SNSCC and DN-SNSCC patients. We also did not find significant differences in overall survival and disease-free survival between IP-SNSCC and DN-SNSCC patients (p = 0.584 and p = 0.238, respectively). The 5-year local failure rate was 52.8% for IP-SNSCC patients, which was significantly higher than for those with DN-SNSCC (31.9%; p = 0.013). The 5-year nodal failure rate was 19.0% for IP-SNSCC patients and 8.5% for DN-SNSCC patients (p = 0.211). The 5-year distant metastasis rate was 8.0% for IP-SNSCC patients and 16.1% for DN-SNSCC patients (p = 0.318). Conclusion IP-SNSCC and DN-SNSCC patients have similar survival outcomes. IP-SNSCC seems to have exhibited a higher local failure rate in our study. We believe that IP-SNSCC is a highly aggressive disease that requires radical treatment. Prophylactic neck treatment should not be omitted in a subset of IP-SNSCC patients.

Sinonasal inverted papilloma (SNIP) is a benign but locally aggressive tumor that has a tendency for recurrence and malignant transformation. The role of human papillomavirus (HPV) in SNIP is controversial. To determine the HPV-DNA prevalence and type distribution in SNIP in two different geographic areas and assess the association between SNIP recurrence and HPV infection, as well as additional potential etiologic factors. Two retrospective cohorts of SNIP patients from Poland and Spain were evaluated. Demographic, tobacco/alcohol use, clinical, and follow-up data were collected. All samples were subject to histopathologic evaluation, DNA quality control, and HPV-DNA detection by PCR. HPV-DNA positive samples and a random sample of HPV-DNA negative cases were further subject to p16(INK4a) analysis. Proportional-hazards models were used to evaluate the risk of recurrence by selected variables. Seventy-nine SNIP patients (46 from Spain diagnosed between 1995 and 2014, and 33 from Poland diagnosed between 2012 and 2017) were included in the study. HPV-DNA was detected in four patients (5.1%), two from each region, and all four were positive for the HPV11 subtype. Seventeen patients (21.5%) experienced recurrence, with a median time to recurrence of 14 months. No association was identified between lesional HPV-DNA positivity, toxic habits, Krouse stage, or malignant transformation and a higher risk of recurrence. The low prevalence of HPV-DNA in SNIPs suggests that HPV is not a main etiology for development of these lesions. With a lack of association between the evaluated factors and recurrence, further research with larger number of patients and additional biomarkers is warranted to further understand predisposing risk factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12105-019-01125-y) contains supplementary material, which is available to authorized users.

Introduction:le Papillome Inversé (PI) est une tumeur bénigne nasosinusienne rare caractérisée histologiquement par une invagination de l'épithélium de surface dans le chorion sous-jacent. Elle se distingue par une forte agressivité locale, une tendance à la récidive et par son risque imprévisible d'association à un carcinome épidermoïde. L'objectif de l'étude était de rapporter les données épidémiologiques, cliniques, paracliniques ainsi que d'évaluer les résultats de la chirurgie endoscopique endonasale. Méthodes:il s'agit d'une étude rétrospective portant sur une série de 13 patients colligés au Service d'Oto-Rhino-Laryngologie du Centre Hospitalier National Universitaire de Fann, du 1erjanvier 2012 au 31 décembre 2017. Ont été inclus dans l'étude tous les patients suivis pour un papillome inversé confirmé à l'examen anatomopathologique. Résultats:l'âge moyen de nos patients était de 44 ans et le sex-ratio (H/F) de 2,25. Tous les patients avaient présenté une obstruction nasale alors que la rhinorrhée était présente dans 53% des cas suivis de l'épistaxis dans 30% des cas. La symptomatologie était latéralisée à droite dans 69% des cas, 23% à gauche et 7% de façon bilatérale. La rhinoscopie antérieure avait permis de visualiser une masse endonasale chez tous les patients. Tous les patients avaient bénéficié d'une TDM; l'IRM avait été réalisée chez un seul patient. L'exérèse du PI par voie endoscopique endonasale avait été effectuée chez 10 patients (76,9%) alors que la voie externe avait été utilisée dans 23% des cas. La chirurgie avait permis de préciser la base d'implantation de la tumeur qui était de l'ordre de 46% dans le sinus maxillaire, 15% dans le cornet inférieur, 15% dans le cornet moyen, 7% dans la bulle ethmoïdale et 7% dans la paroi latérale de la fosse nasale. Un patient avait eu une récidive du papillome inversé après un délai moyen de 26 mois. L'association maligne s'était révélée par un cas de dégénérescence maligne en carcinome épidermoïde. Conclusion:le papillome inversé est une tumeur très agressive. La TDM fournit beaucoup de renseignements à propos de son extension, surtout osseuse. Le traitement est actuellement révolutionné par la chirurgie endoscopique qui offre d'excellents résultats. Mais, il existe néanmoins un risque de récidive après chirurgie qui doit motiver une surveillance au long cours.

Squamous cell papilloma (SCP) is a benign neoplasm of the head and neck. Human papillomavirus (HPV) has been reported to be a tumourigenic factor for SCP. However, not all SCPs are positive for HPV, suggesting that other possible mechanisms are involved in their development. In this study, we examined the mutational status of 51 SCPs using targeted panel sequencing in addition to HPV status using GP5+/GP6+ PCR. HPV DNA was detected in 6 (12%) SCPs, while KRAS and HRAS mutations were detected in 18 (35%) and 17 (33%) SCPs, respectively. Notably, KRAS mutations, HRAS mutations and HPV infection were mutually exclusive. The larynx and trachea (4/7, 57%) were more preferentially infected by HPV than the other sites (2/44, 5%, p = 0.0019) and HPV was associated with multifocal development (4/5, 80%). In contrast, KRAS and HRAS mutations in SCPs were evenly distributed across the anatomical sites and found only in single SCPs. In conclusion, this study demonstrated that HPV was not frequently involved in SCPs and that RAS mutations were more common alterations. In contrast to inverted sinonasal papillomas and oncocytic sinonasal papillomas, SCP may not be a precursor lesion of carcinoma, because these aetiological events in SCP are distinct from squamous cell carcinoma in the same sites.

The necessity to routinely carry out histopathologic examinations of surgically removed polyps in patients with chronic rhinosinusitis with bilateral nasal polyps (CRSwNP) is uncertain. The aim of this study was to describe the histopathology of polyps from a large series of patients who underwent endoscopic sinus surgery for CRSwNP and the rate of neoplasms. This is a retrospective study of the histopathological result of all patients with CRSwNP who underwent functional endoscopic nasal surgery and in whom histologic examination was performed, from 2006 to 2015, in a tertiary medical center. Data on demographics and whether a nasal lesion was suspected for neoplasm prior to surgery were analyzed. Two hundred thirty-five patients underwent bilateral nasal polypectomy and histopathologic examinations of the surgical specimens. The rate of neoplasms in nonsuspicious cases was 2.3% (5 cases) and all were inverted papilloma. To conclude, inverted papilloma and other neoplasms are considered rare incidental findings in patients presenting with bilateral nasal polyps. This study demonstrated a higher rate of the latter than that reported in the literature. Our study further emphasizes that despite the low incidence of these pathologies, a histopathologic examination of every nasal polypectomy is warranted so as not to miss potential serious pathologies. We stress that a routine histopathological examination should be practiced at least in the elderly population.

Background: Sinonasal inverted papilloma (IP) is a benign tumor with a high risk of local recurrence and a potential to malignify and Human papillomavirus (HPV) has been suggested an etiological fa...

Background: Our previous study showed that convoluted cerebriform pattern (CCP)-based reverse tracing method in preoperative magnetic resonance imaging (MRI) is a reliable tool in predicting originating site of sinonasal inverted papilloma (SNIP). This study aimed to determine the underlying pathological mechanism of the preoperative MRI-CCP reverse tracing method by assessing the histopathological changes from the origin to the peripheral sites of SNIP. Methodology: The originating site of SNIP was predicted by preoperative MRI in 30 consecutive patients suspected to have primary SNIP. Samples of SNIP originating and peripheral sites were processed by pathological staining for evaluation of stroma score, micro-vessel density (MVD), and tight junction proteins (claudin-5, zonula occludens (ZO)-1 and occludin) expression. Results: The originating site of SNIP was accurately predicted by preoperative MRI in all patients. Stroma scores, and MVD were significantly greater in the periphery of SNIP than in the originating site. In contrast, Claudin-5 expression in micro-vessels was greater at the originating site than the periphery. Conclusions: More edematous stroma and intensive micro-vessels with defective tight junction in periphery of SNIP result in more contrast agent diffusing and CCP that can only be observed at the periphery of SNIP on T2 and contrast-enhanced T1 weighted MR images, which may be the mechanisms underlying the CCP reverse tracing method.

BackgroundSinonasal inverted papilloma (IP) is a rare tumor of nasal cavity and paranasal sinuses. Its etiology and factors associated with tumor progression remains unclear. Forkhead Box M1 (FoxM1) has also been suggested to serve as an oncogene due to its pivotal roles in cell proliferation and cell cycle regulation. The aim of this study was to characterize the expression pattern of FoxM1 in IP and IP with associated squamous cell carcinoma (IPwSCC).MethodsThe study included 8 subjects with IPwSCC, 17 subjects with sinonasal IP, and 8 normal uncinate tissue (UT) mucosa. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to assess the expression and distribution of FoxM1, polo-like kinase 1 (PLK1), cyclin B1, and cyclin D1 in IP tissues and normal control. The expression of FoxM1, PLK1, cyclin B1, and cyclin D1 in IPwSCC was evaluated using immunohistochemistry.ResultsThe messenger RNA (mRNA) expression of FoxM1, PLK1, cyclin B1, and cyclin D1 was significantly upregulated in IP tissues versus normal UT by real-time PCR (all P values ConclusionFoxM1, a proliferation specific transcription factor, was overexpressed in sinonasal IP and IPwSCC. FoxM1 might be a key molecule associated with growth of IP and malignant transformation of IP into IPwSCC.

Background Recurrent respiratory papillomatosis is a chronic disease of viral origin affecting the larynx, trachea, and lower airways. Inverted papilloma, most commonly originating from the lateral nasal wall, is typically a single, expansile, locally aggressive tumor that remodels bone around the site of origin. Case presentation We report a case of histopathologically proven inverted papilloma occurring in a 50-year-old Caucasian man with recurrent respiratory papillomatosis affecting his nasal cavity, larynx, and trachea. This constitutes the first report of nasal involvement in recurrent respiratory papillomatosis. Viral in situ hybridization studies demonstrated evidence of human papillomavirus in both the septum and middle turbinate subsites. Repeat nasal excision with margin analysis is planned. Conclusions This report emphasizes the importance of considering a broad differential diagnosis in patients with papillomata, and obtaining comprehensive histopathologic evaluation of lesions in multiple subsites in order to rule out inverted papilloma or overt malignant transformation, particularly if high-risk human papillomavirus (HPV) subtypes are identified. Level of evidence 4

Background The prelacrimal approach, termed endoscopic modified medial maxillectomy (EMMM), has recently been applied for treatment of inverted papilloma (IP) in the maxillary sinus. EMMM provides wider access to the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct. Methods We reviewed patients with IP in the maxillary sinus to compare the surgical results obtained by conventional surgery (ie, endoscopic maxillary sinus antrostomy or in combination with the Caldwell-Luc approach) with those obtained by EMMM. Results All patients had a T3 on the Krouse staging system, and the average follow-up time was 46.0 months. Of the 18 patients in the conventional group, recurrence was seen in 3 patients (16.6%). No recurrence was seen in the 27 patients who showed preservation of the inferior turbinate and nasolacrimal duct, and no complications occurred in the EMMM group. Conclusions EMMM is an effective surgical approach that reduces recurrence with fewer complications.

Objective: Sinonasal inverted papilloma (SNIP) is a benign tumor characterized by an aggressive growth, a tendency to recur, and an association with malignancy. However, the precise etiology of SNIP is still unknown. The objective of this study was to identify the expression pattern of speckled protein 100 (Sp100) in the malignant transformation (MT) of SNIP and its correlation with human papillomavirus (HPV)-16 and HPV-18 infections and other clinical features. This would further help in understanding the possible mechanisms for the development of SNIP. Methods: Individual nasal mucosa specimens from 40 patients (25 males and 15 females) and 10 inferior turbinate specimens as controls were included in the present study. The samples were divided into several sections for histopathological examination, HPV DNA detection, and immunohistochemical staining. Results: We observed that as SNIP progressed, the Sp100 protein expression was gradually downregulated, and SP100 localization changed from nucleus to the cytoplasm. Positive rate of HPV infection in the SNIP with MT group was higher than that in the other groups, and Sp100 expression was correlated to HPV infections and SNIP with MT. However, no correlation was observed between Sp100 expression and clinical features, such as age, gender, and smoking. Conclusion: Positive rate of HPV infection is high in the SNIP with MT and has a correlation with Sp100 expression. In addition, the expression of Sp100 is downregulated in SNIP with MT, and Sp100 may play a role in the progression of SNIP.

Objective To compare genome-wide DNA methylation between samples of sinonasal inverted papilloma (SNIP) and squamous cell carcinoma (SCC) samples in order to identify aberrantly methylated genes that might be involved in malignant transformation. Methods Tissue samples were collected from patients. DNA methylation in C-phosphate-G islands and gene promoters was analysed using a DNA methylation microarray kit. The levels of mRNA or protein from aberrantly methylated genes were measured using real-time polymerase chain reaction or Western blot analysis. Results A total of 27 tissue samples were included in this study; 15 SNIP samples and 12 SCCs arising in SNIPs. A total of 11 201 nominally differentially methylated sites were observed between SNIP and SCC arising in SNIPs. Six sites were significantly different at P Conclusions This study demonstrated hypermethylation and abnormal expression of the MIR661, PLEC and OPA3 genes, suggesting a role for their involvement in the malignant transformation of SNIP.

Background: The aim of this study is to demonstrate the effectiveness of the Endoscopic Medial Maxillectomy technique with the preservation of the nasal anatomy and function of the inferior turbinate. Methods: From January 2005 to December 2016, the authors performed 27 Endoscopic Medial Maxillectomy with preservation of inferior turbinate on 26 patients. The most frequent pathologies diagnosed were inverted papillomas (13/27) and antrochoanal polyps (7/27). There were 21 primary lesions and 6 patients had been previously treated. There were 19 males and 7 females. On 11 patients the authors could perform an acoustic rhinometry at 4 months postoperatively. Results: The authors did not find any recurrences. In all cases the authors note the presence of the C-notch being the narrowest area of the nasal cavity, on both the surgical and nonsurgical nasal fossa. The mean area for the C-notch in the nonsurgical nasal cavities was 0.50 cm(2) (0.18-0.82) and it was 0.57 cm(2) (0.08-1.06) in the surgical nasal cavities. The increase of the C-notch after nasal decongestion was 0.10 cm(2) in nonsurgical cavities and it was 0.03 cm(2) in the surgical cavities. The mean distance for the C-notch was 2.18 cm and 2.36 cm before and after nasal decongestion in the nonsurgical fossae. In the surgical cavities were 2.31 and 2.37 cm respectively. Conclusions: The authors' rhinometrics data suggest that Endoscopic Medial Maxillectomy with preservation of inferior turbinate is an effective technique that preserves the anatomic structure and the functions of the inferior turbinate after its resection and reposition.

Objective Neutrophil infiltration in patients with sinonasal inverted papilloma (SNIP) is significantly high. Whether IL-17, which is a potent factor mediating neutrophilic inflammation, is involved in the neutrophilic phenotype of SNIP is investigated in the current study. Study design Laboratorial study. Participants Nasal papilloma and inferior turbinate were collected from patients with SNIP (n = 50) and control subjects with septal deviation (n = 15). Methods IL-17 + cells were evaluated in tissues obtained from patients with SNIP and control subjects with septal deviation, by immunohistochemistry and flow cytometry. Main outcome measures The IL-17 + cells were mainly localised in mononuclear cells and neutrophils, and were up-regulated in the SNIP samples compared with those in the controls. The IL-17 + T-cell subsets mainly included CD4+ (Th17, 60.0%) and CD8+ (Tc17, 30.0%), and both subsets were enhanced in the SNIP samples than controls. The total level of IL-17 + cells was significantly correlated with neutrophil infiltration in the SNIP tissues. Furthermore, the SNIP homogenates could significantly promote IL-17 production in peripheral blood mononuclear cells. Conclusions An increase in IL-17 + cells is evident in SNIP and may be involved in neutrophil infiltration in local tissues. IL-17 could be a potential therapeutic target to relieve the neutrophilic pathological change in SNIP.

Background Sinonasal papilloma has a tendency toward local destruction, recurrence, and malignant transformation. This study aimed to unravel mechanisms in the malignant transformation of sinonasal papillomas using RNA-seq. Methods The cohort consisted of 37 consecutive patients; tumor histology included a continuum spectrum (sinonasal papillomas/dysplastic/carcinomas-in-situ/invasive squamous cell carcinomas). These were microdissected and RNA was subjected to whole-transcriptome shotgun sequencing. Results RNA-seq and pathway analysis showed that the highest expressed genes/potential drivers were development- and differentiation-related genes. The protein expression of six highly upregulated genes (HOXA9, EN1, DUX4, CA9, CD1a, and CK5/6) validated the RNA-seq results. HOXA9 and CA9 were found to be expressed in most of the carcinoma samples but were largely negative in papillomas; all of the CA9-negative carcinomas were recurrent. Conclusions We conclude that sinonasal carcinomas arising from papillomas are mainly defined by overexpressed developmental/homeobox genes, which provide the potential for transformation/plasticity, along with differentiation and proliferation behavior of neoplastic cells. Our results support HOXA9 and CA9 as biomarkers for carcinomas, with CA9 emerging as a predictive marker of recurrence.

Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has been increasingly used in the past decade. Incidental FDG-avid findings are encountered in these studies, several of which with clinical significance. However, the significance of incidental FDG-avid sinonasal findings has not been studied to date.Retrospective cohort study.A single tertiary medical center.The medical records were reviewed of patients with incidental sinonasal positive FDG uptake between 2007 and 2016 who referred for further otolaryngological diagnostic workup.A total of 26 patients were identified, all of whom underwent a diagnostic surgical procedure. Histopathology revealed chronic inflammation (n = 12, 46.1%), malignancy (n = 7, 26.9%), inverted papilloma (n = 4, 15.5%), and fungal infections (n = 3, 11.5%). A unilateral maxillary sinus with FDG uptake was documented for 16 (61.5%) patients. CT evidence of bilateral disease and mucosal or sinus wall thickening correlated with inflammatory disease.Incidental lesions with positive FDG uptake in the sinonasal cavities are at a high risk (40%) of being neoplastic. A diagnostic biopsy is advocated in these cases.

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&rsquo, 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&ndash, 45.6) and metal workers (OR = 5.65, CI = 1.12&ndash, 28.6). The risk of ADC increased in wood (OR = 86.3, CI = 15.2&ndash, 488) and leather workers (OR = 119.4, CI = 11.3&ndash, 1258). On the exact logistic regression, the OR associated to the textile industry was 9.32 (95%CI = 1.10&ndash, Inf) for ADC, and 7.21 (95%CI = 0.55&ndash, 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.