Matteo Gelardi
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which type 2 inflammation, epithelial dysfunction, and tissue remodeling determine severity, recurrence, and treatment response. Although molecular biomarkers have clarified disease endotypes, their routine use remains limited by cost, availability, and invasiveness. Nasal cytology offers a simple, repeatable, and minimally invasive method to assess-at the mucosal surface-both epithelial morphology and the dominant inflammatory infiltrate, whether neutrophilic, eosinophilic, mast cell, or mixed. Clinical-Cytological Grading (CCG) integrates the dominant cytological pattern with selected comorbidities, including asthma, allergy, and NSAID-exacerbated respiratory disease (N-ERD), into a weighted clinical-cytological framework. In the founding cohort, the highest relapse association was observed when mixed eosinophil-mast cell inflammation coexisted with asthma and N-ERD. This review discusses the rationale, clinical relevance, and translational applications of CCG in CRSwNP, addressing eosinophilic and mixed mast cell-eosinophilic inflammation, epithelial morphology, disease recurrence, difficult-to-treat phenotypes, biologic monitoring, and the operative dialogue between nasal cytology and histopathology. By linking cytological findings with selected clinical comorbidities, CCG may support biologically informed patient characterization and may prompt targeted mast cell assessment in tissue. However, its prognostic accuracy, incremental clinical value, and role in therapeutic decision-making require independent external validation.