When Biology Meets Morphology: The Clinical Counterpart of Eosinophil Extracellular Traps in Nasal Cytology

We read with great interest the recent article reporting the prognostic significance of eosinophil extracellular traps (EETs) in chronic rhinosinusitis with nasal polyps (CRSwNP) [1]. The study elegantly demonstrates that eosinophils actively organise extracellular inflammatory structures and that these formations correlate with disease severity and recurrence risk. This work contributes to the growing understanding of type 2 inflammation as a structured and self-sustaining biological process rather than a mere quantitative cellular infiltration. However, the proposed biomarkers remain confined to tissue analysis. Although biologically informative, tissue-based assessment inevitably represents a late and invasive snapshot of the disease, usually obtained only after surgical indication. The translational question therefore becomes not whether EETs are relevant, but whether their inflammatory architecture can be recognised earlier and non-invasively in clinical practice. In this context, nasal cytology offers a complementary perspective. Long before extracellular traps were molecularly characterised, cytological examination of nasal secretions consistently revealed a peculiar eosinophilic organisation composed of free granules, nuclear debris, dense mucin aggregates and Charcot-Leyden crystals. Rather than isolated findings, these elements form a reproducible morphological pattern typical of severe type 2 inflammation and strongly associated with recurrence-prone CRSwNP phenotypes. Notably, Galectin-10 expression has been shown to correlate with clinical-cytological grading and disease prognosis in CRSwNP [2]. From a biological standpoint, this pattern can now be interpreted as the morphological counterpart of extracellular eosinophil activation. EET formation leads to extracellular dispersion of galectin-10 and cytotoxic proteins, which subsequently aggregate and crystallize within the mucus [3] (Figure 1). The Charcot-Leyden crystal therefore represents not merely a by-product of eosinophilic inflammation but the stable endpoint of the same molecular process described in tissue studies. Importantly, this information can be obtained directly from nasal mucus through a non-traumatic sampling procedure, rapidly examined on fresh material and without staining. Phase-contrast microscopy, achievable by simply adding a dedicated condenser to a standard optical microscope, allows immediate visualisation of these organised inflammatory structures in routine clinical settings at negligible cost. Furthermore, nasal cytology is now a standardised and reproducible technique according to an expert-based Delphi consensus, confirming its clinical reliability and applicability [4]. This interpretation bridges the gap between experimental immunology and bedside evaluation: tissue biomarkers explain the mechanism, while cytology visualises its clinical expression in real time. Rather than representing alternative approaches, molecular biomarkers and cytological morphology appear to describe the same phenomenon at different observational scales. EETs provide the mechanistic explanation for patterns clinicians have long observed microscopically. We therefore believe that integrating tissue biology with bedside morphology may enhance translational relevance and facilitate earlier identification of severe CRSwNP phenotypes. Matteo Gelardi conceived the study, analysed the data, interpreted the findings and wrote the manuscript. The author approved the final version of the manuscript. The author has nothing to report. The author declares no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.