Histopathology of Recalcitrant Maxillary Sinusitis Necessitating Endoscopic Medial Maxillectomy.

OBJECTIVES: Endoscopic medial maxillectomy (EMM) is an effective intervention for patients with recalcitrant maxillary sinusitis after previous middle meatal antrostomy. The pathophysiology of refractory maxillary sinusitis is incompletely understood. We aim to identify trends in structured histopathology (SHP) to better understand how tissue architecture changes contribute to refractory sinusitis and impaired mucociliary clearance. METHODS: All patients who underwent EMM or standard maxillary antrostomy for recalcitrant maxillary sinusitis of various forms were included. Retrospective chart review was conducted to collect information on demographics, disease characteristics, comorbid conditions, culture data, and SHP reports. Chi-squared and logistic regression analyses were performed for SHP variables. RESULTS: Forty-one patients who underwent EMM and 464 patients who underwent maxillary antrostomy were included. On average, the EMM cohort was 10 years older (60.9 years vs. 51.1 years; p = 0.001) and more often had a history of prior sinus procedures (73.2% vs. 40.9%; p < 0.001). EMM patients had higher rates of fibrosis (34.1% vs. 15.1%, p = 0.002), and this remained statistically significant when controlling for prior sinus procedures and nasal polyposis (p = 0.001). Cultures positive for pseudomonas aeruginosa (38.2% vs. 5.6%, p < 0.001) and coagulase negative staphylococcus (47.1% vs. 23.5%, p = 0.003) were more prevalent in the EMM group. CONCLUSION: Fibrosis and bacterial infections with Pseudomonas and coagulase negative Staphylococcus were more prevalent in patients requiring EMM. This may contribute to the multifactorial etiology of impaired mucociliary clearance in patients with recalcitrant maxillary sinusitis. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2646-2652, 2024.

Computed Tomography Imaging Patterns of Sinonasal Inverted Papillomas: Comparison of Primary and Recurrent Disease.

OBJECTIVE: To analyze clinical and radiographic features that may impact the rate of focal hyperostosis (FH) on computed tomography (CT) for primary and recurrent sinonasal inverted papillomas (IPs) as well as highlight factors that may affect concordance between FH and IP true attachment point (TAP). METHODS: All IPs resected between 2006 and 2022 were retrospectively reviewed. CTs were read by a neuroradiologist blinded to operative details. IP with malignancy was excluded. Operative reports and long-term follow-up data were evaluated. RESULTS: Of 92 IPs, 60.1% had FH, 25% had no CT bony changes, and 20.7% were revision cases. The recurrence rate for rhinologists was 10.5% overall and 7.3% for primary IPs. Primary and revision IPs had a similar rate of FH (63% vs. 52.6%; p = 0.646) and FH-TAP agreement (71.7% vs. 90%; p = 0.664). Nasal cavity IPs, especially with septal attachment, were more likely to lack bony changes on CT (57.1%) compared to other subsites (p = 0.018). Recurrent tumors were 16 mm larger on average (55 mm vs. 39 mm; p = 0.008). FH (75.0% vs. 60.9%; p = 0.295), FH-TAP concordance (91.7% vs. 74.4%; p = 0.094), and secondary IP (18.8% vs. 20.3%; p = 0.889) rates were similar between recurrent and nonrecurrent tumors. CONCLUSION: Primary and revision IPs have a similar rate of FH and FH-TAP agreement. Nasal cavity IPs are less likely to exhibit bony CT changes. Lower recurrence was associated with smaller size and fellowship training but not multiple TAPs, revision, FH absence, or FH-TAP discordance. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1591-1596, 2024.

Multiple skull base defects in the setting of spontaneous cerebrospinal fluid rhinorrhea; a dual institution view.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a condition of high cerebrospinal fluid (CSF) pressure that presents with CSF leak. The implications of multiple skull base defects (SBD) and associated synchronous CSF leaks have not been previously explored. MATERIALS AND METHODS: A dual institutional case-control study examined multiple SBD's and encephaloceles on the risk of CSF leak and postoperative failures post-repair. IIH patients with CSF leaks and IIH controls without leaks were selected retrospectively. Chi square analysis evaluated for statistically significant alterations in probability with CSF leak development. RESULTS: 192 patients were selected with 108 IIH controls and 84 spontaneous CSF leak cases. Signs and symptoms for IIH controls and CSF leak cases respectively were pulsatile tinnitus (60.2 % and 29.8 %), headaches (96.3 % and 63.1 %), papilledema (74.1 % and 12.5 %), visual field defects (60.8 % and 13 %) (p < 0.001). Encephalocele formation in controls was 3.7 % compared to cases at 91.6 % (p < 0.001). Multiple SBD's in controls compared cases was 0.9 % and 46.4 % respectively (p < 0.001). Subgroup analysis of CSF leak cases showed 15 patients with two CSF leak repairs due to a recurrence. 27 (39.1 %) single leak cases had multiple SDB's while 12 (80 %) recurrent leaks had multiple SDB's (p = 0.004). CONCLUSIONS: Patients with radiographic evidence of multiple SBD's and encephaloceles represent a high-risk population with a propensity for CSF leaks. Secondary SBD's are common in patients with spontaneous CSF rhinorrhea and higher in patients with a recurrence.

Histopathology of Allergic Fungal Rhinosinusitis Versus Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Structured histopathology (SHP) is a method of analyzing sinonasal tissue to characterize endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP). Allergic fungal rhinosinusitis (AFRS) shares several features with certain endotypes of CRSwNP. Our objective was to compare the histopathology of AFRS and eosinophilic CRSwNP to further understand whether they are separate endotypes or disease entities altogether. METHODS: A retrospective review of AFRS and CRSwNP patients undergoing endoscopic sinus surgery was performed. Data were collected on demographics, comorbidities, subjective and objective severity scores, and 13-variable SHP reports. CRSwNP patients with >10 eosinophils per high-power field (eCRSwNP) were included. Chi-squared and t-tests were used for statistical analysis. RESULTS: A total of 29 AFRS and 108 eCRSwNP patients were identified. AFRS patients were younger and more often Black. Symptom severity scores (SNOT-22, Lund-MacKay, and Lund-Kennedy) were uniform between groups. AFRS patients had a higher rate of Charcot-Leyden crystals (41.4% vs. 10.2%; p < 0.001). Severe degree of inflammation, eosinophilic inflammatory predominance, eosinophil aggregates, subepithelial edema, and basement membrane thickening were common in both groups, and their rates were not statistically significantly different between groups. Metaplasia, ulceration, fibrosis, and hyperplastic/papillary change rates were low (<30%) and similar between groups. CONCLUSION: The SHP of eCRSwNP and AFRS are highly consistent, which suggests AFRS is a severe subtype of CRSwNP overall rather than a separate disease entity. This also lends credence to AFRS belonging on the endotypic spectrum of CRSwNP. LEVEL OF EVIDENCE: 3 Laryngoscope, 2023.

Histopathologic features of biologic therapy nonresponders in chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non-type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders. METHODS: A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected. RESULTS: Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as <5 per high power field (55% vs. 31.2%, p = 0.044) and increased basement membrane thickening (100% vs. 78.1%, p = 0.019). The remaining 11 variables did not reach statistical significance. CONCLUSION: Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non-type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS.

A metagenomic analysis of the virome of inverted papilloma and squamous cell carcinoma.

INTRODUCTION: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The role of human papillomavirus (HPV) in its pathogenesis has been controversial. The purpose of this study was to determine the virome associated with IP, with progression to carcinoma in situ (CIS), and invasive carcinoma. METHODS: To determine the HPV-specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from eight controls, 16 IP without dysplasia, five IP with CIS, and 13 IP-associated squamous cell carcinoma (IPSCC). Paired with next-generation sequencing, 48 types of HPV with 857 region-specific probes were interrogated against the tumors. RESULTS: The prevalence of HPV-16 was 14%, 42%, 70%, and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV-18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%, respectively. The assay allowed region-specific analysis, which identified the only oncogenic HPV-18 E6 to be statistically significant when compared with control tissue. The prevalence of HPV-18 E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC. CONCLUSIONS: There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high-risk. Our study demonstrated a trend of increasing prevalence of HPV-18 E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP.

Histopathological Differences in Adult and Elderly Patients With Chronic Rhinosinusitis.

BACKGROUND: Adult and elderly patients with chronic rhinosinusitis (CRS) undergo similar therapeutic management. Few studies have undertaken sinonasal tissue-level comparisons of these groups. This study examines histopathological differences between adults (>18, <65 years) and the elderly (≥65 years) with CRS, with the goal of optimizing medical management. METHODS: In a retrospective cohort analysis, demographic factors, comorbidities, and a structured histopathological report of 13 variables were compared across adult and elderly patients with CRS who underwent functional endoscopic sinus surgery. These cohorts of adult and elderly patients included patients with and without nasal polyps (NP). RESULTS: Three hundred adult (158 aCRSsNP, 142 aCRSwNP) and 77 elderly (38 eCRSsNP, 39 eCRSwNP) patients were analyzed. Mean age of the adult cohort was 44.4 ± 12.4 years, while that of the elderly cohort was 71.9 ± 5.9 years (P < .001). Significantly more adults compared to elderly individuals demonstrated a positive atopic status (79.7% vs 64.0%, P = .004). Elderly patients exhibited higher rates of comorbid diabetes mellitus than adult patients (21.6% vs 10.3%, P = .009). Adults exhibited more tissue eosinophilia (43.4% vs 28.6%, P = .012) and presence of eosinophil aggregates (25.0% vs 14.3%, P = .029) compared to elderly patients, regardless of NP status. Conversely, the elderly demonstrated significantly more fungal elements (11.7% vs 3.0%, P = .004), and trended toward increased overall inflammation (63.6% vs 55.3%, P = .118) and tissue neutrophilia (35.1% vs 27.3%, P = .117), compared to adults. CONCLUSION: Sinonasal tissue of adult and elderly patients with CRS demonstrates clear histopathological differences. Patient comorbidities, in addition to histopathological characterizations, may provide further context for management optimization. LEVEL OF EVIDENCE: 2. SHORT SUMMARY: Sinonasal tissue samples from adult and elderly patients with CRS demonstrate clear histopathological differences. These patient populations also exhibit unique comorbidities. These distinctions have the potential to inform and optimize management of this condition.

Histopathologic Features of Chronic Rhinosinusitis in Diabetic Patients.

OBJECTIVE: To explore how diabetes mellitus impacts chronic rhinosinusitis clinically and on structured histopathology to provide insights on new potential chronic rhinosinusitis endotypes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. METHODS: A retrospective study of chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery from 2015 to 2020 was performed. Structured 13-variable histopathology reports were generated from intraoperative sinonasal specimens. These variables were compared against demographic factors, comorbidities, culture data, and preoperative Lund-Mackay and SNOT-22 scores using logistic regression. RESULTS: There were 411 patients, including 52 diabetics. Diabetes was associated with higher mean body mass index (34.9 vs 29.2; p < .001), age (57.8 vs 48.0; p < .001), and Gram-negative (40.2% vs 22.7%; p < .030) and coagulase-negative Staphylococcus (49.0% vs 28.5%; p = .008) culture rates. Black (23.1% vs 18.7%) and Hispanic (23.1% vs 8.6%) races were more common with diabetes (p = .026). Gender, smoking, polyp status, and Lund-Mackay and SNOT-22 scores did not differ between groups. Diabetics had more fungal elements (13.5% vs 3.3%, p = .018); no other histopathological differences were seen. When controlling for demographic variables and comorbidities, diabetes independently predicted the presence of fungal elements (HR 4.38, p = .018). CONCLUSION: Diabetic chronic rhinosinusitis patients demonstrated increased fungal elements on structured histopathology. Other histopathological features were unaffected by diabetes. These findings may have important implications on the medical and surgical management of diabetic chronic rhinosinusitis patients in which early fungal disease assessment is paramount.

Impact of Treatment Modalities upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis.

Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63-5.76; p < 0.001), diagnosis between 2010 and 2015 (HR: 0.49; 95% CI: 0.26-0.90; p = 0.022), tumor size >5 cm (HR: 2.29; 95% CI: 1.26-4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24-4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status ( p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Histopathologic differences between adult and pediatric patients with chronic rhinosinusitis.

BACKGROUND: Adult and pediatric patients with chronic rhinosinusitis (CRS) may have differing philosophies in therapeutic management. Few studies have examined sinonasal tissue-level comparisons of these groups. This study examines histopathologic differences between children and adults with CRS, with the goal of understanding disease pathogenesis and optimizing medical management for both populations. METHODS: In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery (FESS), demographic factors, pertinent comorbidities, and a structured histopathologic report of 13 variables were compared across pediatric and adult CRS patients with and without nasal polyps (pCRSwNP, pCRSsNP, aCRSwNP, aCRSsNP, respectively). RESULTS: A total of 378 adult (181 aCRSsNP, 197 aCRSwNP) and 50 pediatric (28 pCRSsNP, 22 pCRSwNP) patients were analyzed. Significantly more children compared with adults had a comorbid asthma diagnosis (64.5% vs. 37.2%, p = 0.003). Adults with CRS exhibited significantly more tissue neutrophilia (28.9% vs. 12.0%, p = 0.006), basement membrane thickening (70.3% vs. 44.0%, p < 0.001), subepithelial edema (61% vs. 30.0%, p < 0.001), squamous metaplasia (22.0% vs. 4.0%, p < 0.001), and eosinophil aggregates (22.8% vs. 4.0%, p < 0.001) than children with CRS. The majority (66.5%) of adult CRS patients exhibited a lymphoplasmacytic-predominant inflammatory background, whereas the majority (57.8%) of children with CRS exhibited a lymphocyte-predominant inflammatory background. CONCLUSIONS: Sinonasal tissue of adult and pediatric CRS patients demonstrates clear histopathologic differences. Our findings provide insight into differing pathophysiology, which may enable optimization of targeted therapies for patients in each of these unique clinical groups.

Jugular Foramen Cerebrospinal Fluid Leak Repaired Via the Infralaybryinthine Approach With Adjunct Use of Intrathecal Fluorescein and Stereotactic Navigation.

OBJECTIVE: This report describes a case of a spontaneous cerebrospinal fluid leak at the jugular foramen that was surgically repaired via the infralabyrinthine approach with adjunct use of intrathecal fluorescein and stereotactic navigation. PATIENTS: A 39-year-old woman presenting with clear otorrhea confirmed to be cerebrospinal fluid (CSF) emanating from a defect in the jugular foramen. INTERVENTION: Surgical repair of the skull base defect using an infralabyrinthine approach to the jugular foramen. During surgery, intrathecal fluorescein and stereotactic navigation were used to localize the defect and confirm a successful repair. MAIN OUTCOME MEASURE: Recurrence of a CSF leak. RESULTS: The defect was successfully repaired using the techniques described, resulting in cessation of the patient's CSF leak. There was no recurrence of the CSF leak up to a 4-month postoperative outpatient follow-up. CONCLUSIONS: Diagnosis and repair of spontaneous otogenic CSF leaks in an uncommon location like the jugular foramen are challenging. This report demonstrates the successful use of the infralabyrinthine approach for control of a CSF from the jugular foramen. In addition, use of techniques, such as intrathecal fluorescein and stereotactic navigation that are not routinely used in otology and neurotology allowed for safe, effective repair of the leak in this case.

Impact of Routine Surveillance Imaging on Recurrence in Sinonasal Malignancies.

BACKGROUND/AIM: There is significant variation in post-treatment surveillance imaging for sinonasal malignancies. This study examined the utility of surveillance imaging in detecting recurrence in patients treated for sinonasal malignancies. PATIENTS AND METHODS: We performed a retrospective review on an IRB-approved dataset of patients with sinonasal malignancies treated at a single institution between 2005 to 2021. Patients were categorized into groups based on the frequency of annual imaging and total number of imaging studies. We compared time-to-recurrence between the groups using log-rank test. A two-sided p-value of <0.05 was considered as the threshold for significance. RESULTS: A total of 93 patients were eligible for this study with a median follow up of 42.3 months and 25.8% (n=24) of patients had documented recurrence. Sensitivity and specificity for recurrence based on computed tomography (CT) scans within one year of treatment completion were 50.0% and 19.5%; positron emission tomography/CT was 90.0% and 19.5%; and magnetic resonance imaging was 60.0% and 61.0%, respectively. Regardless of the type of imaging, symptomatic presentation after treatment had a specificity of 91.0% with a positive likelihood ratio of recurrence of 2.95 (95%CI=1.06-8.22). The frequency of scans was not associated with the risk of recurrence (HR=0.55; 95%CI=0.23-1.29, p=0.17). Similarly, no association was noted between the total number of scans and risk of recurrence (HR=0.64; 95%CI=0.27-1.51, p=0.31). CONCLUSION: The total number of frequency of scans within the first year after treatment had no association with time to recurrence of sinonasal malignancies. Symptomatic presentation was strongly associated with recurrence and should be investigated with appropriate imaging.

Adjuvant Therapy and Prognosticators of Survival in Head and Neck Mucosal Melanoma.

OBJECTIVES/HYPOTHESIS: To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). STUDY DESIGN: Retrospective database study. METHODS: The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. RESULTS: Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P = .036). SI (HR 0.425; P = .024) and SRI (HR 0.594; P = .045) were associated with superior OS than SR. Older age (HR 1.607; P < .001), female sex (HR 0.757; P = .006), paranasal sinus localization (HR 1.648; P < .001), T4 classification (HR 1.443; P < .001), N1 classification (HR 2.310; P < .001), M1 classification (HR 3.357; P < .001), and positive surgical margins (HR 1.454; P < .001) were survival prognosticators. Adjuvant radiotherapy use was negatively correlated with older age, oral cavity localization, and M0 or T3 tumors (all P < .05). Adjuvant immunotherapy use was positively correlated with younger age and M1 tumors (all P < .05). CONCLUSIONS: Although SR did not confer survival benefits in HNMM patients, SI and SRI yielded greater OS than surgery alone. SRI was associated with superior survival outcomes than SR. Certain demographic and clinical factors were associated with increased mortality risk. Patient age and certain tumor characteristics were predictors of adjuvant radiotherapy or immunotherapy use. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:584-592, 2022.

Prognostic Indicators of Survival in Sinonasal Diffuse Large B-Cell Lymphoma: A National Cancer Database Analysis.

OBJECTIVES/HYPOTHESIS: This study offers an update on the epidemiologic and prognostic factors and treatment-specific outcomes in patients diagnosed with sinonasal diffuse large B-cell lymphoma (DLBCL). STUDY DESIGN: Retrospective cohort study. METHODS: National Cancer Database was queried from 2004 to 2016 for patients with sinonasal DLBCL. Univariate Kaplan-Meier and multivariate Cox-regression analyses were performed to evaluate the association of suspected prognostic factors with overall survival (OS). RESULTS: A total of 2,222 patients with sinonasal DLBCL were analyzed. OS was 62% at 5 years and 42% at 10 years. Prognostic factors associated with increased survival included African-American race (HR: 0.48, 95% CI: 0.33-0.70), chemotherapy (HR: 0.30, CI: 0.25-0.35), and radiation (HR: 0.80, CI: 0.69-0.93). Prognostic factors associated with decreased survival included patients with Charlson-Deyo scores of 1 (HR: 1.51, CI: 1.25-1.84), 2 (HR: 2.25, CI: 1.67-3.03), and 3 (HR: 2.36, CI: 1.49-3.74) and patients with Lugano stage III (HR: 1.69, CI: 1.09-2.62) and IV (HR: 1.96, CI: 1.46-2.64) disease. Stage-based split multivariate analysis was performed and revealed chemotherapy was independently associated with increased OS in patients with stage I (HR: 0.24, CI: 0.19-0.30), II (HR: 0.17, CI: 0.11-0.28), and IV (HR: 0.41, CI: 0.26-0.64) disease. Radiotherapy was independently associated with increased OS in patients with stage I disease only (HR: 0.67, CI: 0.55-0.83), while immunotherapy was an independent prognostic factor in patients with stage IV disease only (HR: 0.60, CI: 0.37-0.98). CONCLUSION: This study is the largest to date to analyze the association of demographic features and treatment modalities with OS in patients with sinonasal DLBCL. It is the first to investigate the association of immunotherapy with OS in this population. A combination treatment of immunochemotherapy or radioimmunochemotherapy confers increased survival, particularly in patients with advanced disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1515-1522, 2022.

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma.

BACKGROUND: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. METHODS: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. RESULTS: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). CONCLUSIONS: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

The possibility of short-term hypothalamic-pituitary-adrenal axis suppression with high-volume, high-dose nasal mometasone irrigation in postsurgical patients with chronic rhinosinusitis.

BACKGROUND: Medically refractory chronic rhinosinusitis (CRS) is often treated with functional endoscopic sinus surgery (FESS) and high-volume steroid nasal irrigation. While budesonide is the most common steroid irrigation for this indication, mometasone has a superior pharmacokinetic profile, which may allow dose escalation. The safety and efficacy of mometasone at higher concentrations than previously used in treating CRS have not been explored. METHODS: Patients were recruited from a tertiary level clinic between June 2018 and December 2019. Inclusion criteria included adults (>18 years); CRS diagnosis; previous FESS; pre-treatment morning cortisol within normal range; minimum of twice daily high-volume sinonasal mometasone irrigations (total dose of 4 mg) for 12 weeks; and post-treatment morning cortisol measured within 2 weeks following the study period. Patients with potential for endogenous or exogenous disruption of the HPA axis were excluded. RESULTS: 14 patients were enrolled in this prospective cohort study. In all but one patient, pre- and post-treatment morning cortisol levels were not significantly different and were within normal limits (6.7-25.4 µg/dL). Following an uninterrupted 12-week treatment course, no evidence of HPA axis suppression was found (P = 0.915). The single patient who was found to have a low (1.3 µg/dL) post-treatment morning serum cortisol level reportedly received an intraarticular steroid shot several days prior to the blood draw. She remained asymptomatic and her rechecked serum cortisol was within normal limits at 12.3 µg/dL. CONCLUSIONS: High-volume 2 mg twice daily sinonasal mometasone irrigations did not cause HPA axis suppression in a representative sample of patients with refractory CRS post-FESS with normal baseline cortisol levels.

Distinct Histopathologic Features of Complicated Sinusitis.

BACKGROUND: Sinusitis complicated by intracranial or orbital extension can be life-threatening and require emergent intervention. Histologic features of complicated sinusitis have yet to be determined and may have significant implications for understanding pathophysiology. METHODS: A structured histopathology report was utilized to analyze sinus tissue extracted during functional endoscopic sinus surgery (FESS). A total of 13 histopathology variables were compared between patients with complicated sinusitis (CS), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP). RESULTS: About 24 CS, 149 uncomplicated CRSsNP, and 191 uncomplicated CRSwNP patients were analyzed. Nasal tissue from CS and CRSwNP patients demonstrated similar levels of overall inflammation (66.7% vs. 69.6% with moderate/severe inflammation, P = .466). Relative to CRSsNP, CS patients showed significantly greater overall inflammation (66.7% vs. 41.6%, P = .019). CS patients demonstrated significantly fewer eosinophils per high power field (eos/HPF) and eosinophil aggregates compared to CRSwNP patients (20.8% vs. 70.7% with 5+eos/HPF, P < .0001; 4.2% vs. 33.5%, P < .0001). Relative to CRSsNP patients, CS patients demonstrated enhanced neutrophil infiltration (45.8% vs. 28.0%, P = .011). About 91.7% of CS patients demonstrated a lymphoplasmacytic predominant inflammatory infiltrate, compared to 69.8% of CRSsNP and 62.8% of CRSwNP patients (P < .0001). CONCLUSION: Significant histopathological differences were evident in patients with CS, CRSsNP, and CRSwNP. CS patients did not perfectly fit either a CRSsNP or CRSwNP profile, underscoring the importance of delineating the histopathological features of CS. This study offers insight into the histologic aspects of CS, providing initial evidence that it is an aggressive neutrophilic inflammatory process.