The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous cell carcinomas (SCCs) and 38% of papillomas. There is limited data from geographical regions with low prevalence of high-risk (HR)-HPV on the association of HR-HPV in sinonasal neoplasms and on utility of p16 as a surrogate marker. p16 immunohistochemistry, HR-HPV mRNA ISH and quantitative real-time PCR (qPCR) were performed on a retrospective cohort of sinonasal papillomas and SCCs. KRAS mutation analysis was done in oncocytic papillomas. p16 positivity was present in 22/142 cases (15.5%) including eight inverted papillomas, one oncocytic papilloma (OP), and 13 SCC. Among these, mRNA ISH showed HR-HPV in the OP and two SCC, while another SCC was found to harbour HPV18 by qPCR. Two HPV-associated SCCs had foci of OP. mRNA ISH was negative in all p16 negative cases. p16 immunohistochemistry showed 68% concordance with mRNA ISH, and had sensitivity and negative predictive value of 100%; specificity was 67%, and positive predictive value was 14.3%. Association with HR-HPV in sinonasal papillomas and SCC is rare, and may be seen in cases demonstrating oncocytic morphology. p16 immunohistochemistry has low specificity and positive predictive value in low-prevalence populations; thus, reflex direct HR-HPV testing should be performed in p16 immunopositive cases. This two-step approach is viable in resource-limited settings, as the proportion of p16 positive cases is small.

OBJECTIVE: To examine the epidemiology, subtypes, trends over time, and predictive factors for recurrence and malignant transformation of sinonasal papillomas.
METHODS: A retrospective chart review of 118 patients with sinonasal papillomas from 2009 to 2019 was conducted at the University of California, Los Angeles. This study is a follow-up to a previously published study from 2000 to 2009 at the same academic center.
RESULTS: The mean age was at presentation was 58.5 years, with a 2:1 male to female ratio, and average follow-up of 30.1 months. The rate of recurrence after complete resection was 19% with an average of 32.6 months to recurrence. The time to recurrence followed a bimodal distribution with 57% of cases recurring within 24 months (mean = 10) and 43% from 40 to 103 months (mean = 61). The proportion of the inverted papillomas rose from 38% in 2000-2004 to 89.6% in 2015-2019. Patients presenting at a younger age had a higher chance of recurrence (mean age 52 with recurrence vs. 61 without recurrence). Age did not correlate with histopathologic transformation in surgical pathology. Furthermore, histopathological transformation did not raise the chance of recurrence. Smoking, alcohol use, chronic rhinosinusitis, and allergic rhinitis were not associated with any of the outcome measures in this study. The most significant factor predicting recurrence, beside age at presentation, was the history of two or more prior sinus surgeries for papillomas or other reasons (OR = 3.52 and 5.81).
CONCLUSIONS: This study explored the features of sinonasal papillomas as well as the risk factors for recurrence and transformation. Younger age at presentation and two or more prior surgeries for papillomas were associated with recurrence. Time to recurrence followed a bimodal distribution, with late recurrences happenning from 40 to 103 months after surgery, emphasizing the importance of long-term follow-up for timely resection of tumors and prevention of malignancy.

OBJECTIVE: Sinonasal oncocytic papilloma (SOP) is a rare subtype of sinonasal papilloma. There are currently few reports on its clinical features and outcomes after endoscopic surgical resection. This study aims to explore the clinical characteristics of SOP and potential factors predicting tumor recurrence through a single-center retrospective case series analysis.
METHODS: We conducted a retrospective analysis of 69 patients who underwent endoscopic surgery of SOP from June 2012 to April 2019. The data of patients\' demographics, clinical features, follow-up period, and treatment outcomes were collected.
RESULTS: The series includes 43 males and 26 females with an average age of 60.2 years. The tumor commonly involved the nasal cavity (n = 59; 89.4%), followed by maxillary sinus (n = 31; 44.9%), ethmoid sinus (n = 28; 40.6%), frontal sinus (n = 6; 8.7%) and sphenoid sinus (n = 6; 8.7%). The follow-up period ranged from 3 months to 96 months (mean, 34.6 months) and nine patients (13%) developed tumor recurrence during the follow-up period. Univariate analysis found that the recurrence of SOP was significantly related to tumor attachment site, Oikawa tumor stage, and histological dysplasia (p<0.05). Multivariate COX regression analysis found that Oikawa staging system (p = 0.024) and presence of dysplasia (p = 0.04) were significantly related to tumor recurrence.
CONCLUSIONS: SOP had low recurrence rate which was comparable to sinonasal inverted papilloma in the endoscopic era. Our findings also demonstrated that presence of dysplasia is an independent prognostic factor for recurrence free survival.

Inverted papilloma (IP) is a common proliferation of squamous epithelial cells of the sinonasal tract. Although considered benign, IP is known to cause local destruction, has a high rate of recurrence, and a low, but significant rate of malignant transformation. Differentiating an IP from its histologic mimickers is essential for appropriate risk stratification and long-term surveillance. A classic case of sinonasal inverted papilloma is discussed.

UNASSIGNED: Schneiderian papillomas (SP) are aggressive sinonasal tumors that occasionally extend into areas that are surgically unresectable.
UNASSIGNED: evaluate the signifcance of cyclo-oxygenase-2 (COX-2) expression in SP.
UNASSIGNED: Immunohistochemistry for COX-2 was performed on SP samples and middle turbinates from chronic rhinosinusitis without nasal polyps controls obtained during surgical resection between 2009-2017. A positive stain was defined as having 10% or more cells exhibiting diffuse immunoreactivity. Comparisons were performed using Fisher Exact tests, t-tests, and ANOVA.
UNASSIGNED: The study included 67 tumor samples and 9 controls from two academic institutions. The mean age of the SP group was 55.4 years and 53.2 years in the control group (p = 0.71). Thirty-nine (58.2%) SP patients had previous surgery compared to 1 (11.1%) in the control group (p = 0.01). The most common tumor attachment sites were the maxillary (47.8%) and ethmoid (25.4%) sinuses. Fifteen (22.4%) SP samples stained strongly positive for COX-2 and 24 (35.8%) stained weakly positive compared to no positive stains in the control group (p < 0.01). When stratified by COX-2 intensity, there were no statistically significant differences in gender, smoking history, history of previous sinus surgery, site of attachment, papilloma subtype, or future recurrence between SP samples.
UNASSIGNED: COX-2 was overexpressed in 58.2% of SP cases, and strongly positive in 22.4% of cases, compared to no positive staining among controls. No significant differences in COX-2 expression were observed between SP subtypes or recurrent tumors. Further studies are warranted to evaluate COX-2 as a possible therapeutic target in tumors that overexpress the enzyme.

UNASSIGNED: The inverted and oncocytic subtypes of sinonasal Schneiderian papillomas are benign tumors with possible rare malignant transformation and are typically managed with complete surgical resection and close follow-up. While computed tomography (CT) and magnetic resonance imaging (MRI) are mainstays in preoperative evaluation of bony invasion and soft tissue extension of the lesion, their imaging characteristics by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is less well characterized.
UNASSIGNED: To describe the clinical presentation and management of a PET positive sinonasal lesion. To conduct a literature review of FDG uptake in benign sinonasal papillomas.
UNASSIGNED: Case report (n = 1) and literature review of similar cases (n = 32).
UNASSIGNED: We report the case of a 69-year-old man presenting with an isolated left maxillary sinus mass with avid FDG uptake, discovered on PET/CT imaging. An endoscopic left maxillary mega-antrostomy provided successful definitive treatment for final pathologic diagnosis of oncocytic papilloma. Literature review of cases of sinonasal papillomas with avid FDG uptake found that oncocytic papillomas, on average, exhibit greater uptake than inverted papillomas and both may be mistaken as malignancies on PET.
UNASSIGNED: While PET imaging demonstrating avid FDG uptake is associated with an increased risk of malignancy, it does not rule out the possibility of a benign sinonasal papilloma nor other benign inflammatory lesions. Particularly, oncocytic papillomas may have very high FDG uptake and mimic malignant lesions.

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.

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.

OBJECTIVE: 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.
RESULTS: 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.
CONCLUSIONS: 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.

The nasal cavity and paranasal sinuses are covered with ciliated respiratory mucosa of ectodermal origin, known as Schneiderian epithelium, which can give rise to different types of sinonasal carcinomas. A 42-year-old woman with a history of nasal polypectomy 3 years previously presented with nasal obstruction and rhinorrhea. She was found to have a papillary mass involving the left nasal cavity, and the left maxillary and ethmoidal sinuses by radiologic examination. She underwent endonasal resection under the diagnosis of oncocytic papilloma. The resected specimen showed exuberant invasive growth of papillary or inverted architectures of epithelial cells. The neoplastic cells were very bland, showing a round to polygonal shape, low nuclear-to-cytoplasmic ratio, abundant oncocytic cytoplasm, uniform nuclei, indistinct nucleoli, and scarce mitosis. The overall features were identical to those of a recent report of a low-grade papillary Schneiderian carcinoma. The main differential diagnosis is Schneiderian papilloma, and awareness of this novel entity is important for its proper treatment.