Sinonasal Papilloma Research Articles

Papillary‐cystic neoplasms of the middle ear are distinct from endolymphatic sac tumours

Papillary neoplasms of the middle and inner ear are rare and poorly characterised. The current World Health Organization classification divides them into two major subtypes: aggressive papillary tumours (APTs) and endolymphatic sac tumours (ELSTs). The aim of this article is to present two papillary neoplasms of the middle ear that do not fit into either the classic APT category or the classic ELST category, and compare them with three ELSTs. The patients were a 48-year-old female and a 59-year-old male without a history of other neoplasms. Histology showed papillary-cystic growth of predominantly oncocytic (Case 1) or mucinous (Case 2) cells surrounded by a p63-positive basal layer. The overall histology was reminiscent of oncocytic sinonasal papilloma (Case 1) and pancreatobiliary or salivary intraductal papillary mucinous neoplasms (Case 2). Ovarian-type stroma, invasion and malignant features were absent. Immunohistochemistry revealed expression of cytokeratin (CK) 7, but not carbonic anhydrase IX (CAIX) or paired box gene 8 (PAX8) (except for very focal PAX8 expression in Case 1). The TST15 gene panel and HRAS sequencing revealed no pathogenic mutations in BRAF, KRAS, EGFR, AKT1, or HRAS. The TruSight RNA fusion panel revealed an MKRN1-BRAF fusion in Case 1. No fusion was detected in Case 2. The three ELSTs showed classic features of the entity, expressed CK7, epithelial membrane antigen, PAX8, and CAIX, and lacked a basal cell layer. These novel cases suggest that papillary tumours of the ear represent a heterogeneous spectrum of distinct neoplasms unified by a prominent papillary-cystic pattern rather than a single entity. Future studies should clarify whether the MKRN1-BRAF fusion is a defining recurrent driver event, especially in those cases reported as sinonasal-type middle ear papillomas.

EGFR and BRAF mutations in inverted sinonasal papilloma \u2014\xa0a more complex landscape?

Inverted (Schneiderian) sinonasal papilloma (ISP) is a neoplasm derived from mucosa of the sinonasal tract characterized by local aggressive growth, a tendency to recur and an association with sinonasal carcinoma. The etiology of ISP remains unclear. Recently, identical mutations in exons 19 and 20 of the oncogene EGFR were reported in ISP and ISP-associated sinonasal carcinoma. Nevertheless, it remains unclear whether recurring ISPs show identical EGFR mutations at different time points or whether these mutations are identical throughout the respective ISP sample. We used Sanger sequencing to test 60 formalin-fixed paraffin embedded ISP samples from 40 patients regarding mutations in exons 19 and 20 of EGFR—together with exon 15 of BRAF. Overall, 32 samples of 22 patients showed a mutation in EGFR exon 20, whereas 28 samples of 18 patients showed none. No mutation in EGFR exon 19 was found in any sample. Four samples of four patients showed a BRAF exon 15 mutation. Interestingly, samples of four patients exhibited genetic heterogeneity, enabling us to report this in ISP for the first time.

Endoscopic Modified Danker's Approach for Management of Sinonasal Inverted Papilloma: Our Experience.

Sinonasal inverted papilloma (SNIP), Inverting papilloma, Schneiderian papilloma etc. It is a benign tumor with incidence nearly 70% of all sinonasal papilloma and 0.5-4.0% of all sinonasal neoplasms. The most common site of origin is lateral nasal wall and common presenting symptom is nasal obstruction followed by epistaxis. On histopathology examination, it is characterized by invagination of neoplastic epithelium into underlying stroma. With the advent of technology, the endoscopic modified dankers approach became the surgical approach of choice. The present study was undertaken to study its role in management of SNIP with reference to rate of recurrence and malignancy. An observational study was conducted in a tertiary health center in which 40 biopsy proven cases of SNIP, operated by endoscopic assisted modified Danker's approach between September 2008 and January 2019 with minimum follow-up period of 6months were analyzed. Male:Female ratio was 2.33:1. The most common symptom was nasal obstruction (97.5%) followed by rhinorrhoea (87.5%). Using various imaging and diagnostic measures, lateral nasal wall was found to be the most common site of origin. Out of total 40 cases, 9 (27.5%) patients had recurrence, of these, 6 were benign and remaining 3 had malignancy as confirmed by biopsy. Most of the cases of SNIP can be managed endoscopically, although extensive lesions or the lesions with malignant transformation, external approach may be needed so expertise in both endoscopic and conventional techniques is needed. Although most of the recurrences occurred in first 2years, but life time follow-up is advisable.

Clinicopathologic Significance of EGFR Mutation and HPV Infection in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma-related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma-related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non-ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.

MON-260 Sinonasal Papilloma Masquerading as a Pituitary Macroadenoma

Background: Sinonasal tumors are rare, with annual worldwide incidence of approximately 1 in 100,000, and are not commonly considered in the differential diagnosis of pituitary tumors (1). Sinonasal tumors are well known for their invasiveness, tendency to recur and association with malignancy. We present a case of sinonasal papilloma presenting as a large suprasellar mass. Clinical Case: A 61 year-old male with a past medical history including type 2 diabetes mellitus presented with chief complaints of headaches and visual disturbances over the past 6 months. Prior to admission he experienced episodes of left eye midline deviation associated with diplopia. New onset dysphagia associated with leftward tongue deviation prompted him to seek medical attention. The social history was notable for chemical exposures in his work at a hair salon; he is sexually active with his husband. He has had no sexually transmitted infections and has been vaccinated against human papilloma virus (HPV). CT of the brain showed a large sellar mass.A subsequent MRI of the pituitary demonstrated a large destructive mass centered on the clivus elevating the pituitary gland into the suprasellar cistern. The mass measured 6 cm x 4.5 cm in the axial plane with displacement without invasion of the cavernous sinuses. The mass extended anteriorly into the ethmoid sinuses and extended posteriorly into the prepontine cistern displacing the basilar artery.Pituitary hormonal analysis included a 250 mcg Cosyntropin stimulation test resulting with a random cortisol of <1.0 ug/dl rising to 17.7 ug/dl following Cosyntropin administration. Additional anterior pituitary results included FSH of 3.8 mIU/ml (1.5-14 mIU/ml), LH of 1.3 mIU/ml (1.4-7.7 mIU/ml), total testosterone of 230 ng/dl (300-700 ng/dl), and prolactin 11.1 ng/ml (2.6-13 ng/ml). Ophthalmology was consulted for visual field testing which proved normal, however a partial left cranial nerve VI palsy was noted likely secondary to cavernous sinus involvement. A biopsy of the sellar mass was obtained by bedside nasal endoscopy. The initial biopsy was consistent with a non-dysplastic, inverted sinonasal papilloma with negative HPV and P16 serologies. The patient underwent resection of the pituitary mass, with surgical pathology showing superficially invasive squamous cell carcinoma arising from sinonasal papilloma. Conclusion: This is one of the very few cases reported in the literature of a sinonasal papilloma masquerading as a pituitary mass. Sinonasal papilloma should be considered when evaluating large destructive suprasellar tumors. Although a benign tumor, the local aggressiveness of sinonasal papilloma and the potential to give rise to squamous cell carcinoma highlights the significance of identifying this lesion.

Identification of Rare and Common HPV Genotypes in Sinonasal Papillomas.

Sinonasal papillomas are rare, usually benign tumors arising from the Schneiderian membrane. Human papillomaviruses (HPV) can infect differentiating skin and mucosal cells and can induce uncontrolled growth patterns. Their effect on development of sinonasal papillomas has been discussed controversially in recent years. A monocentric, retrospective study was conducted to investigate histopathologic features of sinonasal papillomas and to establish an assay for HPV detection and genotyping in papillomas. Schneiderian papillomas are divided into three groups according to histopathologic features: the largest group are inverted papillomas, followed by fungiform (exophytic) and oncocytic papillomas. HPV screening was performed with high sensitivity by PCR employing My09/11 and 125 consensus primers. Adding a third primer pair (GP5+/GP6+) d increase sensitivity. Reverse hybridization microarrays achieved HPV genotyping better than pyrosequencing in our setting. HPV infection rates were higher in papillomas (46.7%) than infection rates reported for healthy mucosa (up to 13%). P16(INK4a) was not a reliable surrogate marker for HPV infection in sinonasal papillomas. Data from our study endorses the hypothesis that HPV infection promotes formation of sinonasal papillomas. However, apart from HPV genotypes that are frequently found in e.g. anogenital lesions (such as 6, 11, or 16), tissue samples of sinonasal papillomas also displayed infection with "rare" HPV types (such as 58, 42, 83, or 91).

Histopathological study of lesions of nasal cavity and paranasal sinuses

Histopathological study of lesions of nasal cavity and paranasal sinuses - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2020.017, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

Sinonasal papillomas: A single centre experience on 137 cases with emphasis on malignant transformation and EGFR/KRAS status in “carcinoma ex papilloma”

Among the three major histological subtypes of sinonasal papillomas, inverted (ISP) and oncocytic (OSP) sinonasal papillomas tend to undergo malignant transformation to carcinoma. However, criteria determining risk of recurrence and malignant progression have not been established. Recently, EGFR and KRAS mutations were detected to be characteristic for ISP and OSP, respectively. In this study, we analyzed 137 sinonasal papilloma cases (132 ISP and 5 OSP) for clinicopathological characteristics, frequency of recurrences/malignant transformation, and histological types and genetic features of carcinoma ex Schneiderian papilloma. OSP presented at a higher age than ISP (median, 75 vs. 57 years) and affected predominantly females. Overall frequency of recurrences and malignant transformation was 23.1% and 9.5%, respectively. Rates of recurrence (33.3% vs. 22.0%) and malignant transformation (33.3% vs. 8.8%) were higher in OSP compared to ISP, respectively. Carcinomas (n = 10) occurred mostly synchronously, more frequently in females and mainly associated with ISP (n = 9). Squamous cell carcinoma (SCC) was the most frequently associated malignancy. Concordant EGFR (in ISP/associated carcinoma) and KRAS (in the OSP/associated carcinoma) mutations were detected in all successfully analyzed matching papilloma/carcinoma pairs, confirming their shared clonal origin. Results of this large study are in line with recent studies showing frequent EGFR and KRAS mutations in sinonasal carcinoma ex Schneiderian papilloma. As the papilloma component might on occasion be missed on biopsy of synchronous carcinoma ex papilloma, EGFR and KRAS mutation testing represents a promising molecular surrogate for sinonasal “carcinoma ex papilloma”, at the same time offering an opportunity for targeting mutant EGFR in this rare cancer type.

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

Frequent KRAS and HRAS mutations in squamous cell papillomas of the head and neck.

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.

Clinical outcome of endonasal endoscopic prelacrimal approach in managing different maxillary pathologies.

BackgroundThe aim of the study was to evaluate the treatment outcomes of endoscopic prelacrimal recess approaches (EPLAs) in managing different sinus pathologies, analyzing associated adverse events and post-treatment quality-of-life.MethodsWe enrolled 21 consecutive patients (22 lesions) who received endoscopic sinus surgical procedures with EPLAs in two tertiary medical institutes between 2015 and 2018. Quality-of-life and self-rated symptom severity data were collected using the 22-item Sino-Nasal Outcomes Test (SNOT-22) and 10-point visual analog scales (VAS), respectively.ResultsA total of 21 patients (mean age (standard deviation) 51.7 (14.5) years; 16(76.2%) male) were followed up for 12.7 months. The most common symptoms were nasal discharge and nasal airway obstructions. Nine lesions (40.9%) were sinonasal papilloma’s, seven lesions were other types of neoplasms (31.8%; five benign and two malignant), two were trauma-related (9.1%), and four inflammatory diseases (18.2%). Patients with non-papilloma lesions had higher presurgical SNOT-22 than those with papillomas (P-value = 0.021). After EPLAs, non-papilloma patients had significant improvements in SNOT-22 and VAS (P-values = 0.012 and 0.012, respectively), while those with papillomas had only marginally significant improvements in VAS (P-value = 0.061). The most common adverse events was temporary cheek/tooth numbness (n = 11), and patients with sinonasal papillomas were more likely to have post-treatment complications than those with other disease entities.ConclusionsEPLAs were found to effectively manage various sinus diseases. Short-term life-quality improvements were promising. Future large-scale studies with longer follow-up periods are recommended.

Prognostic factors and risk factors for development and recurrence of sinonasal papillomas: potential role of different HPV subtypes.

A retrospective study was conducted to identify and assess potential clinical and molecularbiological risk factors for development and recurrence of sinonasal papillomas (i.e. inverted (IP), fungiform (FP), and oncocytic papillomas (OCP)). Investigated risk factors included age, gender, tumor size and localization, tobacco smoking, regular alcohol consumption, essential hypertension, anticoagulant medication, allergies, surgical approach, and HPV infection. Risk factors were evaluated by regression analysis. Apart from age and incomplete tumor resection, the recurrence of Schneiderian papillomas is independent of conventional risk factors. Patients in this study displayed higher HPV infections rates in IP (38.8%) and in FP (100%) than in healthy mucosa, which is reported 0-5.8% in Germany and central Europe. The proportion of HPV-positive IP decreased with advanced tumor stages: 100% HPV positivity of T1 IP (2/2), 40.9% of T2 IP (9/22), and 35.7% of T3 IP (20/56). Most commonly detected HPV types were HPV 6, 11, and 16; however, patients in this study also displayed HPV types that have rarely or not at all been described in sinonasal papillomas before, such as HPV 58, 42, 83, and 91. Recurrent sinonasal papillomas displayed higher rates of HPV infections than non-recurrent tumors. Young age at initial diagnosis and incomplete tumor resection are risk factors for recurrence of sinonasal papillomas. Our data suggest that HPV infection supports development and/or perpetuation of sinonasal papillomas. Additionally, sinonasal papillomas seem to display a unique subset of HPV genotypes, including genotypes that have not often been described before.

Low prevalence of human papillomavirus infection in sinonasal inverted papilloma and oncocytic papilloma.

The aim of this study was to investigate the role of human papillomavirus (HPV) in sinonasal inverted papilloma (SIP) and sinonasal oncocytic papilloma (SOP) from a single institution and whether p16 can serve as a surrogate marker for HPV infection. This study included 49 subjects with SIP and 36 subjects with SOP. Formalin-fixed paraffin-embedded tissues were used to extract genomic DNA, and HPV detection was performed by utilizing a valid nested polymerase chain reaction approach that can detect all known HPV subtypes. Immunohistochemistry was used to evaluate the expression of p16 in all tumor sections. The presence of HPV DNA was found in 6.1% (3/49) of the SIP patients and 11.1% (4/36) of the SOP patients. All identified HPV subtypes in SIP were high-risk HPV, including HPV-16 (two patients) and HPV-58 (one patient). Regarding SOP, there were three patients positive for HPV-16 and one with low-risk HPV (type 6). In total, 11/49 (22.4%) SIP lesions and 10/36 (27.8%) SOP lesions were considered p16 positive, with p16 staining in more than 70% of tumor cells. There was only one SIP and one SOP that were positive for both HPV (high-risk HPV type 16) and p16 staining. HPV does not play an etiologic role in inverted papilloma or oncocytic papilloma of the sinonasal region. p16 immunostaining should not be used as a surrogate marker to evaluate the HPV infection status in these lesions.

Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papilloma

ObjectivesSinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology. AimsThe aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort. Material and methodsSubjects were identified from our regional center cohort of 88 SIP patients treated between 1984–2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test. ResultsHPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples. ConclusionSince only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.

Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification.

Sinonasal papillomas and carcinomas are uncommon head and neck neoplasms that comprise a broad clinicopathologic and morphologic spectrum, and thus frequently represent a diagnostic challenge for surgical pathologists. Recent molecular interrogation of these tumors has delineated a number of recurrent alterations that correspond to distinct entities with potential diagnostic and/or therapeutic clinical utility. To summarize the salient clinicopathologic, morphologic, and molecular features of sinonasal papillomas and carcinomas. Review of pertinent literature regarding sinonasal papillomas and sinonasal carcinomas. Despite their relative rarity in many surgical pathology practices, sinonasal papillomas and carcinomas frequently demonstrate characteristic morphologic features that are important for accurate diagnosis. Given our emerging understanding of the molecular basis for these tumors, judicious use of available ancillary tools-including immunohistochemistry and in situ hybridization-may be helpful in subsets of cases, whereas additional molecular testing may be useful for diagnostically challenging and/or clinically aggressive sinonasal tumors.

Sinonasal Oncocytic Papilloma-A Series of 20 Cases With Special Emphasis on Recurrences.

ObjectiveReports on sinonasal oncocytic papilloma (SNOP) are scarce. The aim of this retrospective study was to evaluate the clinical features of this rarest form of sinonasal papilloma with special emphasis on the pattern of recurrences and on the potential factors predicting them.Study DesignRetrospective study.MethodsBetween the years 1994 and 2016, 20 patients (mean age 66 years; range 30–87) were diagnosed with SNOP at the Department of Otorhinolaryngology–Head and Neck Surgery, HUS Helsinki University Hospital (Helsinki, Finland). Hospital charts were reviewed to record various medical and sociodemographic patient characteristics, and the archived histological specimens were re‐evaluated. Postoperative follow‐up time varied between 26 days and 167 months.ResultsMaxillary sinus was the most common (60%) tumor location. None of the tissue samples showed dysplasia. Recurrence rate was 39% and the median time span to the first recurrence was 25 months (range 7–71). Smokers had more often a recurrence than nonsmokers (75% vs. 31%). Patients with perioperative purulent rhinosinusitis during the primary surgery had a higher recurrence rate compared with those without (60% vs. 31%). Tumors located in the sinuses recurred more often than those located in the nasal cavity (45% vs. 29%). However, all these findings remained statistically nonsignificant. None of the cases showed malignant transformation during the follow‐up.ConclusionSNOP has a propensity to recur. History of smoking, purulent rhinosinusitis during the primary surgery, and tumor location in the sinuses outside the nasal cavity seem to contribute to an increased trend in the risk of recurrence.Level of Evidence4

Sinonasal inverted papilloma: rate of recurrence and malignant transformation in 44 operated patients

IntroductionAlthough sinonasal inverted papillomas are benign lesions, they are locally aggressive and have a potential malignant transformation ranging from 5% to 15%, with a high recurrence rate. ObjectiveThe aim of this article is to describe the rate of recurrence and malignant transformation in patients with a diagnosis of inverted papilloma who underwent surgery in a tertiary hospital in São Paulo. MethodsWe performed a retrospective analysis of patients diagnosed with sinonasal papilloma who had undergone surgery in a tertiary hospital in São Paulo, between August 1998 and August 2017. A patient chart review was conducted to assess data of patients’ demographics, tumors characteristics, follow-up appointments, recurrence and malignancy. Inverted papillomas were analyzed and classified under the Krouse staging system. ResultsA total of 69 surgeries were performed in patients with diagnosis of sinonasal papilloma. Inverted papilloma was the most prevalent subtype (49 cases ‒ 80.33%), followed by exophytic papilloma (6 cases ‒ 9.84%) and by oncocytic papilloma (6 cases – 9.84%). The recurrence rate was 34.09% for inverted papilloma (15/44) and the mean time of recurrence was 24.6 months. Malignant transformation occurred in 6 patients (13.64%). Three of these patients presented carcinoma in the first surgery and three patients developed carcinoma during the follow-up. ConclusionThe high recurrence rate and malignancy potential allow us to consider inverted papillomas as aggressive tumors. In a tertiary hospital in São Paulo the recurrence rate the mean time to recurrence is 24.6 months. The recurrence after 10 years implies was 34.09% and the need for long-term follow up. It is possible that the high recurrence rate and the high malignant transformation rate we found are due to the large number of tumors discovered at an advanced stage (most of them staged T3 and T4), secondary to poor access to health system, in developing countries.

Abstract 3325: EGFR mutation and protein expression analysis in sinonasal inverted papilloma and squamous cell carcinoma

Abstract Introduction Inverted sinonasal papilloma has been demonstrated to be precursor to a subset of sinonasal squamous cell carcinoma and to carry frequent mutations in EGFR exon 20. The aim of this study was to evaluate EGFR mutation and protein expression as risk marker for malignant transformation of inverted papillomas. Experimental procedures The total number of samples studied was 41 inverted papillomas (ISP) and 32 squamous carcinomas (SCC). We defined patients with one single ISP, with multiple ISP (ISP-ISP) or ISP with malignant transformation (ISP-transformed). In addition, we classified SCC related with ISP (SCC-ISP) and those without relation (SCC de novo). EGFR exon 20 was amplified by PCR and analyzed by Sanger sequencing using the ABI PRISM 3100 and 3730 Genetic Analyzer, (Applied Biosystems, Foster City CA). Immunohistochemistry was performed on an automatic staining workstation (Dako Autostainer Plus; DakoCytomation, Glostrup, Denmark) using the antibody anti-pEGFR clone D7A5 (Cell Signaling Technology, Cambridge, UK). Results were evaluated by two experienced investigators (BV and MM). Results We found EGFR exon 20 mutations in 62% (8/13) ISP, 58% (7/12) ISP-ISP, 63% (10/16) ISP-transformed, 54% (7/13) SCC-ISP and 5% (1/19) SCC de novo. Protein expression of pEGFR was detected in 56% (5/9) ISP, 75% (6/8) ISP-ISP, 47% (7/15) ISP-transformed, 42% (5/12) SCC-ISP and 71% (10/14) SCC de novo. We observed an inverse correlation between EGFR exon 20 mutation and pEGFR expression (p=0.034). Overall survival was significantly better for SCC-ISP compared with SCC de novo (2-year survival 54% and 29% respectively; p=0.030). Conclusions EGFR exon 20 mutations occurred in a high frequency, both for cases with single or multiple ISP and for ISP-transformed, making it a characterizing genetic abnormality for ISP in general. This result also means that the presence of a EGFR exon 20 mutations is not of value as a risk marker for malignant progression. Among the SCC, EGFR exon 20 mutations were notably less and pEGFR expression more frequent in SCC de novo compared to SCC-ISP, suggesting that the EGFR signaling pathway is important in both types of SCC, albeit activated in a different manner. Patients with SCC-ISP had a more favorable clinical course, however, neither EGFR exon 20 mutations nor pEGFR expression demonstrated prognostic value. Nevertheless, EGFR exon 20 mutations can be targeted with specific inhibitors and may be of value for adjuvant therapy for SCC as well as ISP that are difficult to manage. Citation Format: Virginia N. Cabal, Marta Menéndez, Sira Potes-Ares, Blanca Vivanco, Laura Suárez-Fernández, Cristina Riobello, Rocío García-Marín, Fernando López, José Luís Llorente, Mario Hermsen. EGFR mutation and protein expression analysis in sinonasal inverted papilloma and squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3325.

EGFR and KRAS mutations in Chinese patients with sinonasal inverted papilloma and oncocytic papilloma.

Sinonasal inverted papilloma (SIP) and sinonasal oncocytic papilloma (SOP) are uncommon, benign epithelial neoplasms located in the sinonasal region, that have the potential for malignant transformation. A recent study reported that EGFR and KRAS mutations occurred in the majority of Western patients with SIP and SOP, respectively. The aims of this study were to investigate the prevalence of KRAS and EGFR mutations in Chinese SIP and SOP patients, and to study the association between molecular alterations and their clinical features. We retrospectively collected 80 sinonasal papilloma specimens, including 44 cases with SIP, 33 cases with SOP, and three cases with mixed sinonasal papilloma, which harboured elements of both inverted and oncocytic types. Formalin-fixed paraffin-embedded tissues were used to extract genomic DNA, and EGFR and KRAS mutations were evaluated with direct Sanger sequencing. Thirty-five (78%) SIP patients harboured EGFR mutations, and all mutations were exon 20 insertions, whereas no KRAS mutations were detected. In contrast, KRAS mutations were detected in 82% of SOP patients, but no EGFR mutations were detected. Among the three mixed-type cases, two harboured both EGFR exon 20 insertions and KRAS mutations. Another case harboured a KRAS mutation, but no EGFR mutation was detected. SIP and SOP are two clinical entities with different genetic mutational patterns of EGFR and KRAS. Mixed types with elements of both SIP and SOP may harbour both EGFR and KRAS mutations.

Interplay between EBERS and P27 Tumor Suppressor Proteins in Molecular Transformation of Nasopharyngeal and Sinonasal Carcinomas

Epstein barr viruses are well known to induce tumorigenesis in proliferative epithelial tissues. Many studies have implicated EBV in the progression of benign and malignant head and neck tumors by affecting cell cycle proteins expression. This study designed to determine the rates of existential concomitance of EbV in relation to P27 gene expression in tissues from nasopharyngeal and sinonasal lesions. The study included a total number of (183) formalin fixed, paraffin-embedded tissue blocks including 35 inflammatory nasal polyps (INP), 35 sinonasal papillomas (SNP), 65 nasopharyngeal carcinomas (NPC), 18 sinonasal carcinomas (SNC) as well as 30 nasal healthy tissues as control group. After histopathological confirmatory re-examination, a Chromogenic In Situ Hybridization technique (CISH) for EbV-EbERs localization and immunohistochemistry technique (IHC) for p27 expression were performed. The positivity percentages of EBV-EBERs detection in NPC and SNC carcinoma tissues were (86.2% and 88.9%, respectively) while it was (57.1%) in SNP and INP. These results were with highly significant differences (P<0.01). The positively percentages of p27-IHC were (58.5% in NPC, 66.7% in SNC, 51.4% in SNP and 60% in INP) tissues in comparison to control healthy tissues in which only (3.3%) noticed as positive. The statistical analysis shows highly significant differences (P<0.01).