Sinonasal Inverted Papilloma Research Articles

Prognostic significance of p16, VEGF, and p53 expression patterns, Krouse stage, and smoking status in sinonasal inverted papillomas.

The aim of our study is to analyze the staining models for VEGF, p16, and p53, as well as to understand the biology of inverted papilloma caused by smoking. Thirty-one cases, diagnosed with sinonasal inverted papilloma between 2015 and 2019, were included. Demographic data such as age and gender, admission symptoms of the patients, and anatomical location, stage, surgical technique, and recurrence information were obtained from clinical follow-up files. Immunohistochemical staining for p16, VEGF, and p53 were performed on patient materials. In our study, the female to male ratio was 9.33 with an average age of 53.137 ± 13.96 years. Of the patients, 17 were nonsmokers and 14 were smokers. No significant relationship was found between smoking status and relapse and dysplasia. In contrast, a significant relationship between the Krouse stage and dysplasia (P = 0.005) was observed. A similar significant relationship was observed between p16 immunohistochemical expression and dysplasia (P = 0.030). On the other hand, VEGF and p53 immunohistochemical expressions were not significantly related with dysplasia and recurrence. Inverted papillomas are benign tumors that clinically give symptoms similar to nasal polyps. However, recurrence and malignant transformation potential exist and the factors causing this risk are not clearly identified. In our study, no malignant transformation was observed in patients who were admitted to our hospital.

Long-term ambient air pollution exposure and risk of sinonasal inverted papilloma.

Long-term ambient air pollution exposure and risk of sinonasal inverted papilloma.

The Clinical Characteristics in Children with Sinonasal Inverted Papilloma: A Case Report and Review of the Literature.

Sinonasal inverted papilloma (SNIP) is one of the most common benign epithelial tumors but rarely occurs in children. The case of a 9-year-old Chinese boy, who presented with a left maxillofacial hump, nasal obstruction, and left nasal cavity and maxillary sinus masses under nasal endoscopy, is reported. The lesion was first diagnosed as a sinonasal tumor. However, to our surprise, the mass was determined to be an inverted papilloma after a detailed histological examination. We retrospectively reported the clinical data of this case and reviewed the relevant literatures on SNIP. This report aims to provide new insights into the clinical characteristics in children with SNIP and improve the understanding of this disease.

Long-term changes in serum squamous cell carcinoma antigen levels after surgery in patients with sinonasal inverted papilloma

ObjectivesThis study aimed to examine whether serum SCCA levels can be used as clinical markers for monitoring recurrence of sinonasal inverted papilloma (IP) during the follow-up period after surgery. We measured long-term changes in serum levels of SCCA after surgery in patients with IP and examined whether postoperative SCCA levels were associated with IP recurrence. MethodsTwenty-five consecutive patients (13 with primary IPs and 12 with recurrent IPs after their previous surgery) were included in this study. All patients underwent endoscopic or external surgery. Postoperative serum SCCA levels were measured 3 months after surgery and every 3 - 12months during the follow-up. The optimal cut-off values of postoperative SCCA levels to predict subsequent recurrence of IP were evaluated using ROC analysis. ResultsPreoperative serum levels of SCCA were higher than the upper limit of normal range in most patients with both primary and recurrent IP, and significantly decreased after surgery. Thus, the presence of IP was closely associated with elevated serum SCCA levels. Moreover, postoperative elevation of SCCA levels was closely associated with subsequent recurrence of IP. Postoperative SCCA levels in 5 patients with recurrence were significantly higher than those in 20 patients without recurrence. The optimum cut-off value of SCCA levels to predict subsequent recurrence of IP 3 months after surgery was 1.85 ng/ml, with a sensitivity of 100.0 % and a specificity of 90.0 %. ConclusionsThese findings suggest that SCCA can be a tumor marker of IP. It is also suggested that postoperative elevation of SCCA levels is a clinical marker for monitoring the recurrence of IP during the follow-up period. A SCCA cut-off value of 1.85 ng/ml postoperatively may predict the subsequent recurrence of IP with high sensitivity and specificity.

Canine Scent Detection of Sinonasal Inverted Papilloma (SNIP) in Blood Plasma and Nasal Secretions

Canine Scent Detection of Sinonasal Inverted Papilloma (SNIP) in Blood Plasma and Nasal Secretions

Sinonasal inverted papilloma – external versus endoscopic approach

Due to its characteristics, the sinonasal inverted papilloma continues to represent a challenge for the ENT surgeon, be­cause the increased regional aggressivity, the tendency to recurrence, the possibility of multicentric lesions or the po­ten­tial for malignant transformation still raise enough pro­blems, especially related to therapeutic behavior. The authors aim to discuss the clinical case of a patient with such a pathology, presenting the main elements of applied sur­gi­cal therapeutic management. The particularities re­la­ted to the location and origin of the tumor, the type of sur­gi­cal approach used, the advantages and disadvantages of both classical external surgery and transnasal endoscopic sur­ge­ry are highlighted for the successful resolution of such a case and for obtaining superior results in the medium and long term.

Value of a Multidisciplinary Approach in Sinonasal Inverted Papilloma with Extensive Ossification

Patient: Male, 51-year-old Final Diagnosis: Sinonasal inverted papilloma Symptoms: Nasal congestion • nasal mass Medication: — Clinical Procedure: — Specialty: Pathology Objective: Rare disease Background:Inverted papilloma is a benign epithelial lesion of the nasal cavities. Although commonly encountered in clinical practice, it rarely presents with extensive ossification and few cases have been described in the literature.Casa Report:Herein, we describe the case of a 51-year-old man who presented to clinical attention for persistent right nasal obstruction. Magnetic resonance imaging (MRI) and computed tomography (CT) scans of the facial bones showed a lobated lesion with ossification occupying most of the right nasal cavity. The lesion was removed by endoscopic sinus surgery, leaving the surrounding bone structures intact. On pathological examination, mature bone tissue was found within an inverted papilloma. The pathologist contacted the surgeon, who confirmed that no healthy bone tissue was removed during the procedure. Therefore, a diagnosis of inverted papilloma with ossification could be made without the use of ancillary techniques.Conclusions:Inverted papilloma with ossification is a common lesion with a rare feature. Our report investigates the diagnostic difficulties of a paradigmatic case, highlighting the importance of multidisciplinary teamwork in reaching the final diagnosis.

Association of the human papillomavirus infection with the recurrence of sinonasal inverted papilloma: a systematic review and meta-analysis.

Although the role of human papillomavirus (HPV) in sinonasal inverted papilloma (SNIP) has been investigated, the link between HPV infection and SNIP recurrence remains controversial. This meta-analysis aimed to investigate the association between HPV infection and recurrence of SNIP. The PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched (until 16 June 2021) to collect all relevant articles. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed effects model. In addition, subgroup analysis, assessment of publication bias, and sensitivity analyses were performed. Fourteen eligible articles, including 592 patients with SNIP, were included in this study. Pooled analysis revealed that HPV-positive cases exhibited a significantly higher OR of tumour recurrence than HPV-negative counterparts). A significant association between HPV infection and tumour recurrence remained stable in subgroup analyses according to the publication year of the studies. Our meta-analysis demonstrates that HPV infection is significantly associated with the recurrence of SNIP, suggesting the pathological role of HPV in SNIP. These results suggest that HPV infection should be considered in the management of SNIP.

Surgical treatment of sinonasal inverted papilloma.

To highlight how surgery of inverted papilloma has developed during the past year. Moreover, to give our own opinion on the state of research regarding inverted papilloma surgical management. Recent studies covering surgical treatment of inverted papilloma concentrated on the optimum surgical management aiming at complete resection, least morbidity and best outcome, with special interest regarding the maxillary and frontal sinuses. In maxillary sinus inverted papilloma, to avoid empty nose and/or epiphora, recent articles exerted all attempts to preserve the integrity of both the inferior turbinate and nasolacrimal duct, yet offer best exposure of all maxillary sinus walls specially the anterior and inferior ones. These included the new modifications of the prelacrimal and Denker approaches and lateral nasal wall transposition. In frontal sinus inverted papilloma, to avoid an external approach and insure postoperative patency of frontal sinus ostium, the periorbital suspension was introduced and orbital transposition approach was comprehensively utilized especially in far lateral located lesions and/or in supraorbital recess involvement. Associated malignancy is an important issue to identify as management plans significantly differ. Recurrence occurs early within the first 2 years but long-term follow-up is mandatory. Surgical procedures of sinonasal inverted papilloma are planned according to origin rather than the tumor extent. Origin targeted surgery and proper management of the site of attachment are the key to achieve complete surgical resection of sinonasal inverted papilloma. Recent trends advise the least destructive surgical techniques that offer best exposure, complete excision SNIP and least recurrence.

Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study

PurposeLocal recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery.MethodsIn five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo.ResultsIn all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47–112.30) compared to 35.99 (IQR 21.48–57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78.ConclusionsA fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery.Trial registrationNCT03925285.

Technical Note: First Use of Endonasal Confocal Laser Endomicroscopy - Feasibility and Proof of Concept.

Introduction Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses. Further investigation and validation will be necessary.

HPV-Positive Status Is an Independent Factor Associated With Sinonasal Inverted Papilloma Recurrence.

The present study aimed to evaluate human papillomavirus (HPV) occurrence in sinonasal inverted papilloma (SNIP), and to assess factors associated with HPV positivity and SNIP recurrence. Prospective study. We prospectively collected clinical data and fresh tissue specimens from 90 consecutive patients treated for SNIP at Helsinki University Hospital, between 2015 and 2019. Fourteen patients with recurrent SNIP underwent repeated tumor sampling. All tissue specimens were analyzed for the presence of HPV. Factors associated with SNIP recurrence and HPV positivity were assessed. Among 107 SNIP specimens, 14 (13.1%) were positive for low-risk HPV and 6 (5.6%) were positive for high-risk HPV. HPV positivity was associated with an increased risk of recurrence (P= .004). Smoking was significantly associated with HPV positivity in SNIP (P= .01), but a history of HPV-related diseases or patient sexual habits did not correlate with HPV positivity. The recurrence rate was lower among patients with SNIP that underwent an attachment-oriented resection, compared to patients treated without attachment-oriented resections (78.6% vs 25.8%, P< .001). The risk of SNIP recurrence was highly associated with 1) HPV positivity and 2) surgery without an attachment-oriented resection. Oncogenic HPV was rare in SNIP. 3 Laryngoscope, 132:1714-1718, 2022.

NGS-based miRNome identifies miR-449 cluster as marker of malignant transformation of sinonasal inverted papilloma

Objectiveidentification of the miRNA expression profile in sinonasal inverted papilloma (SNIP) as a tool to evaluate the risk of transformation into sinonasal squamous cell carcinoma (SNSCC). Materials and Methodspaired tumour tissues and adjacent normal tissues were obtained from SNIP and SNSCC patients who had undergone surgical resection and used for next-generation sequencing (NGS)-based miRNome analysis. SNIP tissues with concomitant dysplasia (SNIP-DISP) were used as malignant transition samples. By comparing the deregulated miRNAs in SNIP and SNSCC, an miRNA cluster was identified and its physio- and clinical-pathological value was predicted. ResultsNGS identified 54 miRNAs significantly down- and upregulated in SNIP. Among them, the miR-449 cluster was upregulated in SNIP and could differentiate the benign tumour from normal tissue. Notably, the miR-449 cluster was found to be significantly underexpressed in SNSCC, and the cluster markedly changed in SNIP during the malignant transition into SNSCC. miRNA enrichment analysis and GO analysis revealed that miR-449 is involved in apoptotic and cell proliferation pathways. ConclusionsOur findings suggest that miR-449 may be involved in the molecular pathogenesis of SNIP and its malignant transformation into SNSCC. miR-449 might therefore be a useful tumour biomarker in patients with SNIP and may also have the potential to be used as a tool for detecting and monitoring the course of the possible malignant transformation.

Establishment and genetic characterization of cell lines derived from proliferating nasal polyps and sinonasal inverted papillomas

To better understand the pathogenesis of nasal polyps (NPs) and sinonasal inverted papillomas (SIPs), we aimed to establish cell lines from fresh tissues of NPs and SIPs and characterize them. Primary cell cultures were obtained from two NP tissues (NP2 and NP3) and one SIP tissue (IP4). All the cells were polygonal in shape, expressed cytokeratin 14, and had normal diploid chromosome status. HPV58 DNA was detected in NP3. To obtain immortal primary cells, NP2 and IP4 cells were transduced with a combination of mutant CDK4, cyclinD1 and TERT. These cells were thereafter named NP2/K4DT and IP4/K4DT, respectively. HPV58-positive NP3 cells were transduced with TERT alone, the resulting cells named NP3/T. Phenotypic and genotypic identity of original tissues and derived cells was investigated. All the cell cultures with transgenes were confirmed to be derived from their parental cells and primary tumor tissues by analysis of short tandem repeats (STR) and maintained in vitro growth, genetic profiles and gene expression characteristics of the primary cells. These virtually immortalized cells, as well as the primary cells, have potential as in vitro models for studying the pathogenesis of NPs and SIPs and for preclinical study to develop new therapeutic agents.

HPV-Associated Benign Squamous Cell Papillomas in the Upper Aero-Digestive Tract and Their Malignant Potential.

Squamous cell papilloma (SCP) in the upper aero-digestive tract is a rare disease entity with bimodal age presentation both at childhood and in adults. It originates from stratified squamous and/or respiratory epithelium. Traditionally, SCPs have been linked to chemical or mechanical irritation but, since the 1980s, they have also been associated with human papillomavirus (HPV) infection. Approximately 30% of the head and neck SCPs are associated with HPV infection, with this association being highest for laryngeal papillomas (76–94%), followed by oral (27–48%), sinonasal (25–40%), and oropharyngeal papillomas (6–7%). There is, however, a wide variation in HPV prevalence, the highest being in esophageal SCPs (11–57%). HPV6 and HPV11 are the two main HPV genotypes present, but these are also high-risk HPVs as they are infrequently detected. Some 20% of the oral and oropharyngeal papillomas also contain cutaneous HPV genotypes. Despite their benign morphology, some SCPs tend to recur and even undergo malignant transformation. The highest malignant potential is associated with sinonasal inverted papillomas (7–11%). This review discusses the evidence regarding HPV etiology of benign SCPs in the upper aero-digestive tract and their HPV-related malignant transformation. In addition, studies on HPV exposure at an early age are discussed, as are the animal models shedding light on HPV transmission, viral latency, and its reactivation.

Endoscopic Modified Medial Maxillectomy for Inverted Papilloma of the Maxillary Sinus.

Sinonasal inverted papilloma (SNIP) is a benign tumor that can be surgically managed by an endoscopic approach. However, SNIP has a high recurrence rate, mainly due to incomplete resection. This study aimed to analyze the outcomes of endoscopic modified medial maxillectomy in treating SINP originating from the maxillary sinus. The authors retrospectively analyzed 24 patients treated for SNIP via endoscopic modified medial maxillectomy at our institution between August 2014 and June 2019. During surgery, the mucosa involved in the tumor was stripped, and the bone underlying the tumor base was completely excised. Demographic data, surgical technique, location of SNIP attachment, complications, follow-up duration, and recurrence were recorded. Twenty four patients with SNIP were identified (16 males). All patients had Krouse stage-III disease. Eleven patients presented with single attachment and 13 with multiple attachments. None of the patients had any complications during surgery. Four patients had postsurgical facial numbness around the cheek and upper lip. After a mean follow-up of 35.12 ± 14.98 months, no recurrence of SNIP was observed. Endoscopic modified medial maxillectomy is a safe and effective technique for treating SNIP. Recurrence can be reduced by complete excision of the attachment sites.

Nasal-type Natural Killer/T-cell Lymphoma Occurring at the Site from Which a Sinonasal Inverted Papilloma was Previously Resected: A Rare Case Report

Nasal-type Natural Killer/T-cell Lymphoma Occurring at the Site from Which a Sinonasal Inverted Papilloma was Previously Resected: A Rare Case Report

Role of High-Risk HPV Detected by PCR in Malignant Sinonasal Inverted Papilloma: A Meta-Analysis.

Prior studies suggest that there may be a link between human papillomavirus (HPV) infection and malignant sinonasal inverted papilloma (SNIP). This systematic review and meta-analysis was performed to further evaluate this potential association. Systematic review with meta-analysis. The Medline and Embase databases were used to identify case-control studies reporting the risk of malignant SNIP in patients with high-risk HPV subtypes identified by polymerase chain reaction (PCR). Meta-analysis was performed to determine pooled odds ratios (ORs) and 95% confidence intervals (CI). Twenty-one studies were identified, including a total of 841 subjects with SNIP. Seventeen studies were included in the final analysis, as four studies did not have any HPV-positive tumors in either group. A total of 56 malignant SNIP and 551 benign SNIP were ultimately identified. The pooled log-OR was 1.80 (95% CI: 1.03-2.57) for all high-risk HPV subtypes. Stratification by high-risk HPV subtype showed a log-OR of 1.67 (95% CI: 0.88-2.46) for HPV-16 and log-OR of 2.68 (95% CI: 1.30-4.05) for HPV-18. Infection with high-risk HPV subtypes may be associated with an increased risk of malignant SNIP. HPV-18 showed the greatest overall average effect size of the common high-risk subtypes. NA Laryngoscope, 132:926-932, 2022.

Risk factors of malignant transformation of sinonasal inverted papilloma

Objective:To explore the risk factors of malignant transformation of sinonasal inverted papilloma （SNIP）, and to improve the accuracy of preoperative diagnosis of tumor. Methods:The clinical data of 89 patients with sinonasal inverted papilloma （SNIP group, n=60） and malignant transformation of sinonasal inverted papilloma （IP-SCC, n=29） were analyzed retrospectively. Clinical symptoms, medical history, endoscopic examination, characteristic of sinonasal CT scan and MR imaging were collected and compared between two groups. Then the indicators with significant differences between the two groups were used for binary logistic regression analysis. The logistic regression model was established to predict the malignant transformation risk factors of inverted papilloma and the prediction ability of the regression model was estimated. Results:The significant differences between the two groups were: symptoms, including nasal obstruction, purulent mucus, blood in the nasal discharge; long-term smoking history; tumor attached with purulent mucus; CT scan showing bone destruction of the orbital wall and skull base; MR Imaging showing convoluted cerebriform pattern （CCP） sign, intraorbital involvement, and dural enhancement of the skull base. The results of logistic regression analysis showed that the risk factors of malignant transformation of SNIP were blood in the nasal discharge, long-term smoking history, tumor with purulent discharge, orbital wall destruction on CT scan, disappearance of CCP and orbital involvement on MRI. The accuracy rate of regression model for predicting malignant transformation of IP is 75.0%, and the accuracy rate for benign inverted papilloma is 96.7%, and the overall accuracy of the model is 89.8%. Conclusion:The risk factors for predicting malignant transformation of SNIP are blood in the nasal discharge, long-term smoking history, tumor with purulent discharge, orbital wall destruction on CT scan, and disappearance of CCP sign and orbital involvement on MRI. It's necessary to analyze all of clinical factors in order to improve the accuracy of preoperative diagnosis of sinonasal inverted papilloma.

P-132 Own experience in the treatment of patients with sinonasal inverted papilloma in Belarus

P-132 Own experience in the treatment of patients with sinonasal inverted papilloma in Belarus