Mast cells: The forgotten players in type 2 inflammation - From nasal cytology to chronic rhinosinusitis with nasal polyps and beyond.

Mast cells represent key regulators within type 2 inflammation and contribute significantly to the pathophysiology of chronic inflammatory airway diseases. Nasal cytology has enabled their consistent identification, highlighting how their interaction with eosinophils influences inflammatory persistence, tissue remodeling, and disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP). In contrast, conventional hematoxylin-eosin histopathology does not reliably visualize mast cells, potentially limiting comprehensive cellular characterization. Through cytological assessment, distinct inflammatory endotypes have been defined, including nonallergic rhinitis with mast cells and nonallergic rhinitis with eosinophils and mast cells, which may represent stages along a continuum progressing toward CRSwNP. The Clinical-Cytological Grading integrates cellular patterns with clinical parameters, identifying eosinophil-mast cell coinfiltration as a marker associated with increased disease severity and recurrence risk. Evidence from both sinonasal and extra-nasal mucosae, including eosinophilic esophagitis, further supports the relevance of mast cells within the broader network of type 2 inflammation. As therapeutic strategies increasingly target specific inflammatory pathways, accurate cellular endotyping becomes essential for refining risk stratification and optimizing biologic therapy selection. Integrating nasal cytology with histological and molecular approaches offers a pragmatic framework for advancing precision medicine in type 2 inflammatory diseases.