Sinonasal Papilloma Research Articles

Malignant Transformation of Exophytic Sinonasal Papilloma: Case Report

Malignant transformation of exophytic sinonasal papilloma (SP) is exceptionally rare. The authors present a case of a 48 years old woman who presented to hospital with unilateral nasal obstruction, a tissue mass in the right nasal entrance...

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal-inverted papilloma to squamous cell carcinoma.

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISP-associated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.

Respiratory Epithelial Adenomatoid Hamartoma


 A 65-year-old man consulted with a history of chronic snorting with a sensation of obstruction in the left side of the nasopharynx particularly when in supine position. A few days prior to consult, the patient had blood-tinged nasal discharge, thus this admission. No other symptoms were reported.
 
 Nasal endoscopy showed a sessile exophytic lesion with a vaguely nodular surface, seen as a polypoid nasopharyngeal mass on Computed Tomography scan. (Figure 1)
 
 Excision of the mass was performed. Received in the surgical pathology laboratory was a 1.8 x 1.5 x 0.6 cm red to brown, rubbery to firm, vaguely ovoid mass with a nodular external surface. Cut section showed a light gray solid surface. 
 
 Microscopic examination shows a broad-based exophytic mass with invaginations of the surface epithelium and proliferated glands within the stroma. (Figure 2) The glands are tubular or variably dilated - many are lined by a respiratory-type epithelium with goblet cells and a thickened basement membrane, while the tubular glands are lined by a monolayered cuboidal epithelium. (Figure 3) Based on these features, we signed the case out as a respiratory epithelial adenomatoid hamartoma (REAH).
 
 REAH is a benign proliferation of sinonasal tract glands derived from the surface epithelium.1 It occurs primarily in male adults, with a median age in the sixth decade of life. Most cases arise in the posterior nasal septum, while less common sites of involvement include other parts of the nasal cavity, the nasopharynx, and paranasal sinuses.2 Common symptoms include nasal obstruction, stuffiness, and epistaxis.1,3,4
 
 REAH presents as a polypoid lesion and may measure up to 6 cm in widest diameter.1 Microscopically, there is a proliferation of small to medium-sized glands dispersed in abundant stroma. Invagination of the glands from the surface epithelium may be seen.3 The glands are round to oval, lined by respiratory-type epithelium with admixed goblet cells. Thickened basement membranes surround some of the glands, and smaller seromucinous glands lined by cuboidal epithelium may also be admixed among the latter. Other alterations may include squamous, chondroid, and osseous metaplasia.1,4
 
 Rarely, REAH may occur synchronously with inverting sinonasal papillomas or inflammatory polyps.1 It may be mistaken for these two entities along with sinonasal low-grade adenocarcinomas. Careful attention to the typical morphology including absence of an infiltrative growth pattern and atypia allow distinction from these entities particularly the malignant mimics.3 A related entity is a seromucinous hamartoma with which REAH is believed to form a morphological spectrum.1
 
 REAH is benign and complete excision confers cure.1 Malignant transformation has not been reported.1,3,4

Sinonasal squamous cell carcinoma and EGFR mutations: a molecular footprint of a benign lesion.

Molecular targeted therapy against EGFR kinase domain mutations has been successfully established for lung cancer. These mutations have now also been reported in head and neck tumours, particularly in inverted sinonasal papillomas (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in head and neck squamous cell carcinomas and papillomas. We examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head and neck papillomas or polyps. EGFR mutations were detected in 24 (30%) of 80 sinonasal squamous cell carcinomas (SNSCCs) and in 19 (90%) of 21 ISPs. Notably, 15 (88%) of 17 SNSCCs that developed along with ISPs harboured EGFR mutations in both components, whereas EGFR mutations were detected in nine (14%) of 63 SNSCCs without any papilloma component. Analysis to detect other known driver oncogene mutations - KRAS, BRAF and HER2 - was also performed; none of these mutations was detected in SNSCCs. The other 208 non-sinonasal carcinomas and 37 non-ISP head and neck papillomas or polyps did not harbour EGFR mutations. Taken together with the specific involvement of EGFR mutations in ISP, a molecular benign lesion trail suggests that 26 (33%) of 80 SNSCCs developed in association with an ISP. SNSCCs with EGFR mutations may be biologically distinct among head and neck cancers.

The Prevalence of Human Papillomavirus Infection in Benign Sinonasal Lesions: A Single-Center Retrospective Analysis

It is suggested that just like cigarette smoking and occupational exposure, HPV plays a significant role in the etiology of benign sinonasal lesions. It is evident through literature review that low-risk HPV types 6 and 11 are usually confined to benign lesions, whereas the reverse is true for the oncogenic HPV types 16 and 18. Our aim was to seek the prevalence and the types of HPV coinfection in a benign head and neck surgical specimen. Benign specimens from head and neck sites with available HPV wide spectrum testing and immunohistochemistry for HPV and p16 were retrospectively reviewed (January 2011 to October 2015). Thirty-seven sinonasal surgical specimens were identified, requiring direct examination and enough changes warranting a biopsy. On histology, these revealed focal viral cytopathic changes, inverted papillomas, squamous hyperplasia, squamous papilloma, and verrucous hyperplasia type of morphology. The results for HPV wide spectrum, HPV 6, 11, 16, 18, 33, 35, and 45, were collected. Thirteen of 37 benign lesions showed positive results for HPV wide spectrum. Two of 13 came out to be positive for HPV 16 with positive p16 staining on immunohistochemistry. The remaining (11/13) cases were positive by HPV wide spectrum for HPV 6 and HPV 11 (n = 7 with HPV 6, n = 4 with HPV 11) showing focal p16 staining. Twenty-one of 37 showed focal p16 staining, which was interpreted as negative. Current studies link HPV to at least a proportion of benign sinonasal papillomas. HPV 6 and HPV 11 seem to be present in a large number (30%) of these benign lesions in our cohort. This corresponds with the available literature (30%-35%). Although two of our cases did show infection with HPV 16, there was no dysplasia identified in the lesion.

Abstract 4342: Inverted sinonasal papilloma and associated carcinoma-transcriptome analysis and out-hoxing developmental genes

Abstract Introduction Sinonasal papillomas, a group of benign epithelial tumors of the sinonasal tract, are classified into 3 distinct histologic types: exophytic, endophytic and oncocytic . Associated clinical problems include a tendency towards local destruction, recurrence and malignant transformation. While controversy persists in determining the optimal therapeutic approach in a given patient, prognostic markers identifying patients who will benefit from more aggressive treatment and novel molecular targeted therapies are urgently needed. The majority of endophytic papillomas require a lengthy period for malignant transformation, but the trigger underlying the malignant changes remains obscure. The present study aimed to identify underlying mechanisms in the malignant transformation of sinonasal inverted papillomas using RNA seq. Material and methods Samples from 36 consecutive patients formed the study material and were microdisected from FFPE. Pools of RNA were subjected to expression profiling using whole-transcriptome shotgun sequencing. For validation, differentially expressed candidates were analyzed by IHC. Results The studied cohort showed a continuum, with 14 sinonasal papilloma (11 inverted type, 2 oncocytic and 1 exophytic type), 2 sinonasal papilloma with dysplastic changes, 3 carcinoma in situ and 17 invasive squamous cell carcinoma arising in a papillomatous background (majority being associated with inverted type papilloma). Differential gene expression profiles from 14 papillomas, 14 squamous carcinomas versus 4 normal sinonasal mucosa were generated and compared to each other. 1447 genes and noncoding transcripts were detected as differentially expressed with fold change >2 and false discovery rate < 0.035. These genes and transcripts were annotated and computationally analyzed using the Ingenuity Pathway Analysis program. The highest expressed genes and potential drivers were predominantly development- and differentiation-related genes. To validate the RNA-Seq results, we used IHC assessing the protein expression of 5 highly upregulated genes considered important. These candidate genes were HOXA9, EN1, DUX4, CA-IX, and CK5/6 with expressions at 30%, 50%, 60%, 60% and 95% respectively. Conclusion We assume that sinonasal papillomas are mainly defined by high number of overexpressed developmental/homeobox genes, which provide the potential for transformation/ plasticity, along with differentiation and proliferation behavior of neoplastic cells. The data form the basis for understanding cell fate determination and cellular homeostasis in the normal sinonasal mucosa and the contribution of different mucosal components to the etiology/ molecular pathology of sinonasal dysplasia and carcinoma. Citation Format: Achim H. Bell, Ehab Y. Hanna, Randal S. Weber, Victor G. Prieto, Diana Bell. Inverted sinonasal papilloma and associated carcinoma-transcriptome analysis and out-hoxing developmental genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4342.

Abstract 3420: Discovery of genetic alterations governing sinonasal squamous cell carcinoma tumorigenesis

Abstract Tumors of the sinonasal tract are uncommon, and comprise 5% of all cancers of the head and neck (H&N). Approximately 50-80% of sinonasal malignancies are sinonasal squamous cell carcinoma (SNSCC). Unlike H&N cancers, tobacco smoking does not seem to play a key role in the development of sinonasal tumors and the exact etiology and molecular mutations governing SNSCC tumorigenesis are not well understood. Inverted sinonasal papilloma (ISP) is a locally aggressive, benign epithelial neoplasm arising in the paranasal sinuses which has a high recurrence rate and transforms to SNSCC in 10% to 25% of cases, and therefore represent an intermediate step in SNSCC progression. Due to its uncommon nature, there is still a significant knowledge gap in our understanding of SNSCC pathogenesis and genetic mutations associated with SNSCC progression have not yet been characterized. To this end, we performed whole exome sequencing (WES) and RNA-Seq on 4 ISPs and matched SCCs samples collected from the same patients. For each patient, DNA extracted from matched lymphocytes was used as a DNA sequencing control, whereas matched uninvolved mucosa was used as a tissue specific control for RNA-Seq. 285 and 602 non-synonymous aberrations were identified across the preneoplastic lesions and tumors respectively. Interestingly, genes associated with adverse survival in HNSCC patients (such as EGFR, FAT1 and IGF1R) were mutated in more than 1 dysplastic lesion. PIK3CA was among the most mutated genes in invasive neoplasms. Notably, in three patients we identified mutations that were present in both preneoplastic and invasive neoplasms, which included cancer driver genes actionable in HNSCC and other solid malignancies (such as PIK3CA, TP53, FAT1 and EGFR). RNA-Seq analysis of the same samples revealed a subset of genes whose expression level sequentially increased or decreased from normal tissue, to early lesions to SNSCC. Interestingly, expression of genes associated with survival, migration, invasiveness and inhibition of apoptosis (such as SET, RAD21, NPM1, PTPN11, CLIP1, KIF5B, EGFR, NRAS, KRAS, MET, MYCL and CCND1) consecutively increased along the tumor progression in all three analyzed, whereas expression of tumor suppressors (such as PTCH1, IKZF1, GAS7, FOXP1, NTRK3 and LRP1B) was downregulated. Although our data suggest that preneoplastic ISP lesions may be clonally related to SCC in some cases, validation of these observations in a larger specimens' cohort is warranted to further delineate the mechanisms underlying the SNSCC tumorigenesis. Citation Format: Adrian D. Schubert, Nyall R. London, Justin A. Bishop, Esther C. Broner, David Sidransky, Evgeny Izumchenko. Discovery of genetic alterations governing sinonasal squamous cell carcinoma tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3420.

Imaging features of benign mass lesions in the nasal cavity and paranasal sinuses according to the 2017 WHO classification.

The World Health Organization (WHO) 2017 classification of head and neck tumors has been just published and has reorganized tumors of the nasal cavity and paranasal sinuses. In this classification, three new entities (seromucinous hamartoma, NUT carcinoma, and biphenotypic sinonasal sarcoma) were included, while the total number of tumors has been reduced by excluding tumors if they did not occur exclusively or predominantly in this region. Among these entities, benign tumors were classified as sinonasal papillomas, respiratory epithelial lesions, salivary gland tumors, benign soft tissue tumors, or other tumors. In contrast, inflammatory diseases often show tumor-like appearances. The imaging features of these benign tumors and tumor-like inflammatory diseases often resemble malignant tumors, and some benign lesions should be given attention in the follow-up period and before surgery to avoid recurrence, malignant transformation, or massive bleeding. Understanding the CT and MR imaging features of various benign mass lesions is clinically important for appropriate therapy. The purpose of this article is to describe the clinical characteristics and imaging features of each of clinically important nasal and paranasal benign mass lesions, as classified according to the WHO 2017 classification of head and neck tumors, along with some inflammatory diseases.

Human papillomavirus (HPV) and somatic EGFR mutations are essential, mutually exclusive oncogenic mechanisms for inverted sinonasal papillomas and associated sinonasal squamous cell carcinomas

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. 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. 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). Collectively our data show that EGFR mutations and HPV infection represent essential, alternative oncogenic mechanisms in ISP and ISP-associated SNSCC.

Histopathological profile of sinonasal lesions with brief clinical correlation: experience in a tertiary care centre

Background: Sinonasal lesions are a common finding in Otorhinolaryngology outpatientdepartment. Most commonly they present withnasal obstruction. Clinically many of these lesions resemble eachother but they have multiple differential diagnosis ranging from congenital, inflammatory, traumatic to neoplasticcauses that needs histopathological confirmation. Objectives: This study was undertaken to study the various histopathological patterns of sino-nasallesions, theirclassification and relative distribution of various lesions with regard to age and sex in our setting. Material and Methods: This was a retrospective study of Sino-nasal lesions specimens thatwas received at histopathology section of Department of Pathology, Hamdard Institute of Medical Science andResearch andover a period of two years from June 2014 to May 2016. Results: A total of 62 cases of sino-nasal lesions were reported during the study period. Ageranged from 5 years to 75 years with malepredominance. Among all the lesions forty five (45) were non-neoplastic, ten (10) benign and seven (7) were diagnosedas malignant tumors. Inflammatory polyp was the commonest non-neoplastic lesion while Sinonasal Papilloma was the commonest benign lesion and Sinonasal carcinoma was themost common malignancy. Conclusions: Sino-nasal lesions comprises of wide spectrum of lesions but their presenting clinicalmanifestations are very limited. Hence, on the basis of clinical picture various nonneoplastic, benign and malignantlesions may mimic each other. Histopathological diagnosis forms the mainstay of diagnosis in these lesions whichmay even reveal clinically unsuspected rare malignancies as seen in our study.

Combined Minimally Invasive Supraciliary and Transfacial Approach for Large Tumors with Skull Base and Sinonasal Involvement.

Tumors invading both the anterior skull base and the sinonasal area have traditionally been accessed via largely invasive open craniofacial approaches. Minimally invasive extended endoscopic endonasal approaches have recently become increasingly available but have anatomical limitations and require incremental experience and thus high patient volume. Our objective was to assess the applicability of a novel combination of the minimally invasive supraciliary incision and the limited maxillofacial osteotomy as a combined surgical approach for large tumors invading both the anterior skull base and the sinonasal area. The well-established technique of supraciliary incision with a 2.5× 3.0-cm craniotomy was combined for the first time with limited facial translocation approach. This series involves 11 cases (female/male ratio 4:7; ranging in age from 6 to 61 years). Intracranial tumor propagation with intranasal and ethmoidal extension was detected in all patients. The pathologic diagnoses included adenocarcinomas, esthesioneuroblastoma, rhabdomyosarcoma, sinonasal papilloma, meningioma, and neurofibroma. The postoperative approach-related mortality rate was zero. No case of cerebrospinal fluid leak was detected. The 3-year survival rate was 70%. The limited transfacial approach in combination with a supraciliary extension is associated with minimal mortality and morbidity and facilitates gross total tumor removal. We highly recommend this approach for the surgical treatment of large tumors invading both the anterior skull base and the sinonasal area, especially for those being out of indication for extended endoscopic endonasal surgery.

Sinonasal Papillomas in a Private Referral Otorhinolaryngology Centre: Review of 22 Years Experience

ObjectivesTo evaluate the clinical presentation, treatment outcome and follow-up of all patients managed with sinonasal papillomas (SP), at a tertiary private otorhinolaryngology centre in Caracas (Venezuela). Material and methodsWe reviewed 94 patients with SP that were treated at our otolaryngology centre, from July 1st 1993 to June 31st 2015. The demographic data, clinical features, radiological findings, anatomical origin, disease extension into the adjacent structures, surgical approaches performed, histopathology outcomes, recurrent risk, malignant transformation rate and coadjuvant therapies were assessed. ResultsSixty-five patients (69.1%) were male and 29 (30.9%) female with an average age of 44.5 years (range 9–80 years). All patients underwent endoscopic sinus surgery. The most commont histologic subtypes of SP were inverted papilloma (58 patients; 61.7%), fungiform papilloma (35 patients; 37.2%) and oncocytic papilloma (one patient; 1.1%). SP was associated in 2 patients with undifferentiated squamous cell carcinoma. Twelve patients (12.8%) had disease with extension beyond the sinus without associated malignancy. All these patients received adjuvant treatment with advanced techniques of radiotherapy. The mean duration of the follow-up period was 9 years and 2 months. Eighteen patients (19.1%) had recurrent disease during the entire course of follow-up. ConclusionsComplete endoscopic surgical removal of SP is the treatment of choice. In less endoscopically accessible tumours, with peripheral extension or incompletely resected, Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy may be indicated. Timely post-operative endoscopic follow-up with biopsy of suspected lesions is important for early detection of recurrences and associated malignancy.

New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull base.

The World Health Organization recently published the 4th edition of the Classification of Head and Neck Tumors, including several new entities, emerging entities, and significant updates to the classification and characterization of tumor and tumor-like lesions, specifically as it relates to nasal cavity, paranasal sinuses, and skull base in this overview. Of note, three new entities (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were added to this section, while emerging entities (SMARCB1-deficient carcinoma and HPV-related carcinoma with adenoid cystic-like features) and several tumor-like entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal hamartoma) were included as provisional diagnoses or discussed in the setting of the differential diagnosis. The sinonasal tract houses a significant diversity of entities, but interestingly, the total number of entities has been significantly reduced by excluding tumor types if they did not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. Refinements to nomenclature and criteria were provided to sinonasal papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall, the new WHO classification reflects the state of current understanding for many relatively rare neoplasms, with this article highlighting the most significant changes.

Ringertz Tumor with Malignant Transformation

ABSTRACT Introduction An inverted papilloma is a benign tumor that is found in the nasal cavity or paranasal sinuses. Inverted papilloma accounts for approximately 0.5 to 2.0% of all nasal tumors. While it is considered benign, an inverted papilloma can destroy the surrounding bone. In a small number of cases (5-15%), an inverted papilloma may be found with a squamous cell carcinoma; one such case is reported. Case report A 70-year-old male presented with complaints of right-sided nasal blockage, which progressively increased over time and nasal discharge since one and half years with occasional history of epistaxis. On anterior rhinoscopic examination, there was a fleshy polypoidal mass filling the right nasal cavity. Contrast-enhanced computed tomography revealed a soft tissue density mass filling maxillary sinus and posterior choana with mild enhancement. Endoscopic medial maxillectomy was performed with complete removal of mass. Histopathological diagnosis was given as inverted sinonasal papilloma with malignant transformation. The patient was referred to a cancer reference center for treatment and received combined radiotherapy and chemotherapy. Patient was disease free at 6-month follow-up. Conclusion An inverted papilloma is a benign tumor with a propensity for malignant change. For these reasons, inverted papilloma should be treated like malignant tumor of the nasal cavity and paranasal sinuses. How to cite this article Prinja S, Davessar JL, Luthra H, Kaur M. Ringertz Tumor with Malignant Transformation. Clin Rhinol An Int J 2017;10(1):39-41.

OSPs and ESPs and ISPs, Oh My! An Update on Sinonasal (Schneiderian) Papillomas.

Sinonasal (Schneiderian) papillomas are benign neoplasms that arise in the sinonasal tract. Since their initial descriptions, sinonasal papillomas have triggered debate regarding their classification, etiology, rate or predictors of malignant transformation, and other issues. While significant strides have been made in recent years, there are still aspects of sinonasal papillomas that remain unclear even now. This review will serve to update the practicing pathologist on the current understanding of sinonasal papillomas.

Clinical effects of p53 overexpression in squamous cell carcinoma of the sinonasal tract: A systematic meta-analysis with PRISMA guidelines.

Background:The level of p53 protein expression in sinonasal squamous cell carcinoma (SNSCC) has been estimated, but the results remain inconsistent and the point of consensus has not been reached. This study was first determined to evaluate the clinical effects of p53 expression in SCC of the sinonasal tract.Methods:According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, the potential literature was searched from diverse databases. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to assess the strength of association between p53 expression and SNSCC.Results:Final 17 eligible studies were included in a total of 258 cases and 748 controls. The result of p53 expression was shown to be notably higher in SNSCC than in benign sinonasal papillomas and normal sinonasal mucosa (OR = 26.93, P < 0.001; OR = 39.79, P < 0.001; respectively). Subgroup analyses of ethnicity revealed that p53 expression had significant association with SNSCC in Asian and Caucasian populations in cancer versus benign sinonasal papillomas or normal sinonasal mucosa. The expression of p53 was notably higher in moderately or poorly differentiated SNSCC than in well-differentiated SNSCC (OR = 3.51, P = 0.021), while p53 expression was not associated with histological type.Conclusion:The results suggested that p53 overexpression may be correlated with the carcinogenesis and progression of SNSCC. The p53 gene may become a novel drug target of SNSCC. Additional studies on the correlation of p53 expression with clinicopathological features are needed.

Papilomas rinosinusales en un centro de referencia otorrinolaringológico privado: revisión de 22 años de experiencia

ObjectivesTo evaluate the clinical presentation, treatment outcome and follow-up of all patients managed with sinonasal papillomas (SP), at a tertiary private otorhinolaryngology centre in Caracas (Venezuela). Material and methodsWe reviewed 94 patients with SP that were treated at our otolaryngology center, from July 1st 1993 to June 31st 2015. The demographic data, clinical features, radiological findings, anatomical origin, disease extension into the adjacent structures, surgical approaches performed, histopathology outcomes, recurrent risk, malignant transformation rate and coadjuvant therapies were assessed. ResultsSixty-five patients (69.1%) were male and 29 (30.9%) female with an average age of 44.5 years (range 9-80 years). All patients underwent endoscopic sinus surgery. The most commont histologic subtypes of SP were inverted papilloma (58 patients; 61.7%), fungiform papilloma (35 patients; 37.2%) and oncocytic papilloma (one patient; 1.1%). SP was associated in 2 patients with undifferentiated squamous cell carcinoma. Twelve patients (12.8%) had disease with extension beyond the sinus without associated malignancy. All these patients received adjuvant treatment with advanced techniques of radiotherapy. The mean duration of the follow-up period was 9 years and 2 months. Eighteen patients (19.1%) had recurrent disease during the entire course of follow-up. ConclusionsComplete endoscopic surgical removal of SP is the treatment of choice. In less endoscopically accessible tumours, with peripheral extension or incompletely resected, Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy may be indicated. Timely post-operative endoscopic follow-up with biopsy of suspected lesions is important for early detection of recurrences and associated malignancy.

Activating KRAS mutations are characteristic of oncocytic sinonasal papilloma and associated sinonasal squamous cell carcinoma.

Oncocytic sinonasal papillomas (OSPs) are benign tumours of the sinonasal tract, a subset of which are associated with synchronous or metachronous sinonasal squamous cell carcinoma (SNSCC). Activating EGFR mutations were recently identified in nearly 90% of inverted sinonasal papillomas (ISPs) - a related tumour with distinct morphology. EGFR mutations were, however, not found in OSP, suggesting that different molecular alterations drive the oncogenesis of these tumours. In this study, tissue from 51 cases of OSP and five cases of OSP-associated SNSCC was obtained retrospectively from six institutions. Tissue was also obtained from 50 cases of ISP, 22 cases of ISP-associated SNSCC, ten cases of exophytic sinonasal papilloma (ESP), and 19 cases of SNSCC with no known papilloma association. Using targeted next-generation and conventional Sanger sequencing, we identified KRAS mutations in 51/51 (100%) OSPs and 5/5 (100%) OSP-associated SNSCCs. The somatic nature of KRAS mutations was confirmed in a subset of cases with matched germline DNA, and four matched pairs of OSP and concurrent associated SNSCC had concordant KRAS genotypes. In contrast, KRAS mutations were present in only one (5%) SNSCC with no known papilloma association and none of the ISPs, ISP-associated SNSCCs, or ESPs. This is the first report of somatic KRAS mutations in OSP and OSP-associated SNSCC. The presence of identical mutations in OSP and concurrent associated SNSCC supports the putative role of OSP as a precursor to SNSCC, and the high frequency and specificity of KRAS mutations suggest that OSP and OSP-associated SNSCC are biologically distinct from other similar sinonasal tumours. The identification of KRAS mutations in all studied OSP cases represents an important development in our understanding of the pathogenesis of this disease and may have implications for diagnosis and therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A clinicomorphological study of Schneiderian Papilloma

Background: Schneiderian papilloma are benign epithelial neoplasm of three subtypes- exophytic, oncocytic and inverted. The objective of the study performed is to illustrate the histopathological patterns and clinical presentation of schneiderian papilloma subtypes. Sinonasal papillomas are benign yet aggressive neoplasm characterized by high recurrence rate and associated with malignancy. Method: A prospective study was performed of schneiderian papillomas diagnosed in a period of three years. Results: Thirty five patients of sinonasal papilloma who underwent sinus surgery were observed. There were 25(71%) male and 10(29%) female subjects diagnosed at an average age of 53 years(range 10-74years). The three subtypes were classified as exophytic(13 cases); inverted(19cases) and oncocytic papilloma(3cases). Conclusion: Inverted papilloma are the most common sinonasal papilloma. Key Words: Exophytic, Inverted, Oncocytic, Sinuses

Role of ESS in sinonasal papillomas

Role of ESS in sinonasal papillomas