There is limited understanding of the impact of anti-IL5 treatment on nasal polyp tissue biology in chronic rhinosinusitis with nasal polyps (CRSwNP). This study examined nasal polyp tissue cellular proteome and transcriptome responses to anti-IL5 treatment in CRSwNP utilizing spatial profiling. GeoMx Digital Spatial Profiling of 80 proteins and 1,833 messenger RNA targets in the polyp stroma and the whole transcriptome (18,815 messenger RNA targets) in polyp epithelia was undertaken on sinonasal biopsies collected from 20 individuals with eosinophilic CRSwNP before and after 16 and 24 wk of mepolizumab treatment. Anti-IL5 therapy in patients with eosinophilic CRSwNP had significant tissue biological impact. Treatment-related changes in polyp stroma proteins associated with checkpoint inhibition (PD-1), neutrophil degranulation (CD6b, CD44, STING1), and the innate immune system (CD14, CD68, STING, CD163) were identified in a protein interaction network. Transcriptionally, there were significant reductions in gene sets associated with the reactome terms "innate and adaptive immune system," "neutrophil degranulation," and "TGFβ receptor signaling in epithelial-to-mesenchymal transition within polyp stroma," as well as "enhancing antioxidant pathways." In polyp epithelia, increases in gene sets associated with the reactome terms "cilium assembly" and "keratinization" and a reduction in the regulation of KIT signaling were observed. Spatial profiling demonstrates that the effects of anti-IL5 treatment within nasal polyp tissue extend beyond simple eosinophil reduction to regulation of innate and adaptive immune cells and in improving epithelial barrier biology. The clinical relevance of changes to improved barrier function may relate to quality-of-life metrics observed previously with anti-IL5 treatment.

BACKGROUND:A greater benefit of biologics is observed after surgery in Type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). However, the extent of surgery remains undefined in many studies. This study evaluated the extent of surgery on disease control in patients receiving biologics for refractory Type 2 dominant CRSwNP. METHODS:A cross-sectional study was performed on patients with CRSwNP treated with biologics for ≥ 6 months at a tertiary center. All patients had undergone prior sinus surgery, which included a sphenoethmoidectomy and then extension via Draf I, IIa, IIb, IIc, or III. Disease control was defined as having a SNOT-22 ≤ 30, endoscopic modified Lund-Mackay ≤ 4, and the absence of rescue therapy within 6 months. Comparisons were made across surgical and biologic groups, and logistic regression was used to identify factors associated with disease control. RESULTS:A total of 159 patients were assessed (age 50.9 ± 12.8 years, 45.3% female). Disease control was achieved in 49.1% of patients. Disease control was greater with extended surgery (Draf III 60.8% [49.7%-70.8%] vs. Draf IIc 68.3% [53.0%-80.4%] vs. Draf IIa 8.7% [2.4%-26.8%] vs. Draf I 0% [0.0%-19.4%]; p < 0.001). The control was similar across biologic types (anti-IL-4αR 63.3% [45.5%-78.1%] vs. anti-IL-5/5R 45.7% [37.3%-54.3%]; p = 0.083). On regression, extended surgery (Draf III + IIc) was associated with disease control (Draf III/IIc vs. Draf IIa/I OR: 110.2 [12.7-14,682.5]) but not biologic type (anti-IL-4αR vs. anti-IL-5/5R OR: 2.2 [0.7-7.2]). However, class switching had already occurred in 15.1% of patients initially treated with anti-IL-5/5R. CONCLUSIONS:Disease control was greatest in CRSwNP patients who had both extended sinus surgery and optimized biologic treatment.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nasal mucosa characterised by a heterogeneous immune cell infiltrate and that is largely unresponsive to clinical management. The pathology of CRSwNP remains poorly understood and new approaches are needed to study this condition. We used CosMx™ Spatial Molecular Imaging (SMI) and CellScape™ Spatial Immune Profiling (SIP) to examine the molecular and proteomic spatial biology of nasal polyps. CosMx SMI was undertaken on formalin-fixed paraffin-embedded sections of sinonasal biopsies. Slides were analysed with the Human 6,000-plex RNA Discovery Panel. CellScape SIP was conducted on serial sections to validate spatial proteomic immune cell signatures. Of 116,372 cells profiled and 3,993 genes detected, 15 distinct cell types and 231 pairwise ligand-receptor interactions were identified. T-cell niches and plasma subsets were co-localised near epithelial cells. Pairwise ligand receptor interactions were identified between fibroblasts and plasma cells, T-cells, granulocytes and B-cells. Cellscape SIP confirmed the presence of immune cell types and allowed characterization of immune cell neighbourhoods in the epithelial compartment. Our findings advance the understanding of the heterogeneous immune microenvironment in eCRSwNP and identify potential therapeutic targets needed for new treatment options. Collaborative supportive funding from GSK Immune Mechanisms of Human Disease (HUM)

ABSTRACT Background Type 2 inflammation dominates eosinophilic chronic rhinosinusitis (eCRS) and adult onset asthma. IL‐4, ‐5, and ‐13 are prominent disease mediators. Disease control can be achieved with biologic therapies. However, despite some patients entering remission, others experience poor control. Aim We aimed to describe eCRS patients treated with anti‐IL‐5R antibody (benralizumab) and assess characteristics between responders and those requiring class switching to anti‐IL‐4/13R (dupilumab). Method A retrospective cohort study was performed on consecutive adult patients with eCRS and asthma who had commenced benralizumab. Disease control was defined as controlled or poorly controlled (EPOS2020 partly control/uncontrolled). Poorly controlled patients were switched to dupilumab. Baseline and post‐IL‐5R characteristics including age, sex, 22‐item Sinonasal Outcome Test (SNOT‐22), Asthma Control Questionnaire (ACQ) score, and serum/tissue eosinophilia were assessed. Disease control post‐class switching was reassessed. Factors predicting poorly controlled disease on anti‐IL‐5R therapy were sought. Results Fifty patients were assessed (51.44 ± 12.73 years, 56% female). Poorly controlled disease on anti‐IL‐5R requiring class switch to dupilumab was seen in 42%. Poorly controlled patients were younger (46.14 ± 10.76 vs. 55.28 ± 12.83 years, p = 0.01) with higher baseline SNOT‐22 (61.42 ± 19.19 vs. 42.32 ± 21.55, p < 0.01). Baseline ACQ scores and eosinophil count (0.78 ± 0.49 vs. 0.62 ± 0.34 × 10 9 cells/L, p = 0.23) and were similar between groups. In the poorly controlled patients on anti‐IL‐5R therapy, eosinophilia had reduced in both serum (0.78 ± 0.5 vs. 0.02 ± 0.1 × 10 9 cells/L, p < 0.01) and tissue (>100 cells/HPF: 100% vs. 29%, p = 0.01). Class switching resulted in disease control for 65%. Conclusion Neither eosinophilia nor its reduction predicted a non‐responder group to anti‐IL‐5R therapy. While the eosinophil population may be a good marker for the CRS phenotype seen in nasal polyps, it is unlikely to be the cell population driving the disease process.

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Context The recent WHO 2022 Classification of pituitary tumours identified a novel group of ‘plurihormonal tumours without distinct lineage differentiation (WDLD)’. By definition, these express multiple combinations of lineage commitment transcription factors, in a monomorphous population of cells. Objectives To determine the expression of stem cell markers (SOX2, Nestin, CD133) within tumours WDLD, immature PIT-1 lineage and acidophil stem cell tumours, compared with committed cell lineage tumours. Methods Retrospective evaluation of surgically resected pituitary tumours from St Vincent’s Hospital, Sydney. Patients were selected to cover a range of tumour types, based on transcription factor and hormone immunohistochemistry. Clinical data was collected from patient files. Radiology reports were reviewed for size and invasion. Samples were analysed by immunohistochemistry and RT-qPCR for SF-1, PIT-1, T-PIT, SOX2, Nestin and CD133. Stem cell markers were compared between tumours WDLD and those with classically “mature” types. Results On immunohistochemistry, SOX2 was positive in a higher proportion of tumours WDLD compared with those meeting WHO lineage criteria, 7/10 v 10/42 (70 v 23.4%, p = 0.005). CD133 was positive in 2/10 tumours WDLD but 0/41 meeting lineage criteria, P = 0.003. On RT-qPCR, there was no significant difference in relative expression of stem cell markers (SOX2, CD133, Nestin) between tumours with and WDLD. Conclusions Our study is the first to biologically characterise pituitary tumours WDLD. We demonstrate that these tumours exhibit a higher expression of the stem cell marker SOX2 compared with other lineage-differentiated tumours, suggesting possible involvement of stem cells in their development.

OBJECTIVE:To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment. METHODS:A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis. RESULTS:The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease. CONCLUSION:The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated.

Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 +/- 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R-2 = -0.417, p = 0.010), smoking history (63.31 +/- 7.93 vs 54.44 +/- 9.21, p = 0.0060), and family headache history (68.13 +/- 7.01 vs 54.94 +/- 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 +/- 12.14 vs 47.18 +/- 10.15, p = 0.027) and sphenoid sinus invasion (58.87 +/- 8.97 vs 51.29 +/- 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R-2 = -0.682, p < 0.001, MIDAS: R-2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 +/- 18.68 vs 12.00 +/- 17.54, p = 0.0030). Conclusions Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.

Head and neck cancers, representing the seventh most common malignancy globally, have seen a shift in causative factors from traditional smoking and alcohol use to human papillomavirus (HPV) infection, now accounting for up to 80% of oropharyngeal cancers. We identify the cellular and clonal mechanisms underlying immune avoidance and metastasis by analysing single-cell and spatial genomic data from primary and metastatic cancers. We first map the clonal evolution of malignant cells based on the accumulation of mutations. We identify metastasising clones based on mutational similarity scores between cells in the primary and lymph node metastasis. Genomic analysis of metastasising and non-metastasising clones identified virally mediated protein translation relief ( P =4.24x10-24) pathway underlying metastatic expansion. We show that in metastatic clones, this process is driven through upregulation of transition-initiating factors, EIF4E ( P =1.5x10-13) and EIFG1 ( P <2.22x10-16), and suppression of regulatory kinases EIF4EBP1 ( P =2.1x10), EIF2AK2 ( P <2.22x10-16), and EIF2S1 ( P <2.22x10-16). We subsequently identify that metastatic clones have a corresponding downregulation of the JAK/STAT pathway and immunoproteasome genes PSMB8 ( P <2.22x10- 16) and PSMB9 ( P <2.22x10-16), suggesting these clones escape immune surveillance through decreased INF inflammatory response and antigen presentation. We validate these results using spatial RNA-seq data, where metastatic cancer clones show decreased cell-to-cell interactions with CD4 T-effector memory cells (CD4TEM) ( P =0.0077), CD8 T-exhausted cells (CD8Ex) ( P =0.0191), and innate lymphoid cells (ILC) ( P =0.04). Finally, we demonstrate that the upregulation of cap-independent translational drives cell proliferation in metastatic clones through the expression of translation initiation factors ( EIF4G1: P <2.22x10-16). Our results provide evidence of the mechanisms by which virally induced cancer clones lead to advanced disease and poor prognosis in patients. ### Competing Interest Statement The authors have declared no competing interest.

BACKGROUND Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. METHODS A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. RESULTS A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002). CONCLUSION Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.

Flow cytometry (FCM) is widely used in the diagnosis of mature B‐cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B‐cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM.

Objectives To determine the clinical utility of assessment of tumour invasion, markers of proliferation, and the French clinicopathological classification in pituitary tumour prognostication. Methods This is a retrospective evaluation of adult patients undergoing pituitary surgery at Oxford University and St Vincent's Hospitals, between 1989 and 2016, with at least 12 months of clinical data. Invasion was assessed radiologically, proliferative markers (Ki67, mitotic count, p53) by immunohistochemistry. Tumours were graded according to the clinicopathological classification. Intra- and interlaboratory variability of histopathology reporting was evaluated. Outcomes (1) Tumour recurrence (radiological or reintervention & GE;12 months postoperatively) and/or (2) "aggressive behaviour" (& GE;4 interventions and/or invasive tumour with recurrence/reintervention between 12 and 24 months postoperatively). Results A total of 386 patients were included, age at surgery was 56 (interquartile range [IQR] 41-67) years, 54% were male, and median follow-up was 90 months (range 44-126). Tumours were predominantly clinically nonfunctioning (252, 65%), with overall 53% invasive, and 10% that demonstrated & GE;2 proliferative marker positivity. Recurrence was predicted by invasiveness (hazards ratio [HR] 1.6 [1.10-2.37], P .02), elevated mitotic count (HR 2.17 [1.21-3.89], P .01), grade (2b vs 1a HR 2.32 [1.06-5.03], P .03), and absence of gross total resection (HR 3.70 [1.72-8.00], P .01). Clinically defined aggressiveness was associated with elevated Ki67, mitotic count, and invasiveness. Ki67 reporting methodologies showed moderate correlation across laboratories (Phi 0.620), whereas p53 reporting reproducibility was poor (Phi 0.146). Conclusions Proliferative markers, including Ki67 and mitotic count, but not p53, are important in predicting the development of aggressive pituitary tumour behaviour.

Background Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. Objective This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. Methods A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. Results 38 participants were included (51.7 +/- 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 +/- 16.3 vs 44.5 +/- 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (tau(b) = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 +/- 1947 vs 746 +/- 519 cells/mm(2), p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. Conclusions Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

KEY POINTS:Culturable bacterial colonization is similar between type 2 CRS phenotypes Staphylococcus aureus coinfection is similar between eosinophilic CRS and CCAD Patients with CCAD were younger, consistent with current knowledge of the disease.

Objective:Pituitary tumours comprise a pathologically and clinically diverse group of neoplasms. Classification frameworks have changed dramatically in the past two decades, reflecting improving understanding of tumour biology. This narrative review examines the evolution of pituitary tumour classification, from a clinical perspective.Results:In 2004, pituitary tumours were classified as 'typical' or 'atypical', based on the presence of markers of proliferation, Ki67, mitotic count and p53. In 2017, the new WHO marked a major paradigm shift, with a new focus on lineage-based classification, determined by transcription factor and hormonal immunohistochemistry. The terms 'typical' and 'atypical' were omitted, though the importance of proliferative markers Ki67 and mitotic count was acknowledged. The recent WHO 2022 classification incorporates further refinements, specifically recognising some less common types that may represent less well-differentiated tumours. Whilst 'high risk' tumour types have been identified, further work is still required to improve prognostication.Conclusions:Recent WHO classifications have marked significant progress in the diagnostic evaluation of pituitary tumours, though shortcomings and challenges remain for both clinicians and pathologists in managing these tumours.

The Switch/Sucrose Non-Fermentable (SWI/SNF) protein complex functions as a tumour suppressor through chromatin remodelling. Mutations in genes that encode complex subunits have been identified in a rare subset of aggressive poorly differentiated malignancies across anatomical sites, including thorax, gastrointestinal, genitourinary and sinonasal tracts.1,2 The mutations are independent predictors of poor outcome. Cases presenting as isolated lymphadenopathy are uncommon.3 We report a case of a male in his fifties, with a heavy smoking history, who presented with an isolated right supraclavicular lymph node metastasis from a clinically and radiographically unknown primary site. A core biopsy and subsequent neck dissection revealed a poorly differentiated metastatic carcinoma with a non-specific immunophenotype that included loss of two SWI/SNF complex subunit genes, SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) and SMARCA2. This unusual presentation highlights that a diagnosis of SMARC deficient carcinoma should be considered in poorly differentiated cervical lymph node metastases. Increased recognition of these malignancies may improve diagnosis, prognostication, therapeutic management and patient outcomes. References 1. Nambirajan A, Jain D. Recent updates in thoracic SMARCA4-deficient undifferentiated tumor. Semin Diagn Pathol 2021; 38: 83–89. 2. Agaimy A. SWI/SNF-deficient sinonasal neoplasms: an overview. Head Neck Pathol 2022; 16: 168–178. 3. Nambirajan A, Parshad R, Goyal A, Mithun NK, Jain D. Innocuous clinical presentation of a SMARCA4-deficient thoracic sarcoma arising in a patient with chronic empyema thoracis. Pathology 2019; 51: 657–659.

Background Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = −8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = −2.37, p = 0.02). Conclusion Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.