Conventional and Liquid-based Cytology of Eosinophilic Sialodochitis: Evidence of Eosinophil Extracellular Trap Cell Death (EETosis)?

Summary: Introduction: Eosinophilic sialodochitis (ES) is a rare, allergy-related, eosinophilic disease of the salivary glands, characterized by recurrent gland swelling, due to duct obstruction by eosinophil-rich mucus plugs or periductal eosinophilic infiltration. The primary aim of this study was to delineate the cytomorphological features of ES both in conventional and liquid-based cytology (LBC) samples. Materials and Methods: We present the preliminary first-year findings of a 5-year prospective study of all ES cases diagnosed in the cytopathology department of Aretaieion Hospital (start date: 01/01/2023). Demographics, clinical presentation and other relevant medical data were obtained from the treating physicians. All samples (mucus plugs, obtained after gland massage) were processed using both conventional and LBC techniques but also as cell blocks. Cytomorphology, immunocytochemical and cell block features were recorded and correlated to the remaining clinicopathological data. Results: A cytological diagnosis of ES was documented only in 2 cases (male to female ratio: 1/1; mean age: 43.5 years) throughout the preliminary study period, reflecting the extremely low prevalence of this rare condition. An abundance of eosinophils and fewer ductal cells, often in close proximity to eosinophils or, more rarely, with features of mucous metaplasia, were the main cytomorphological findings (Fig.1 and 2). Mast cells, staining positive for CD117/KIT, and/or tryptase were also observed (Fig. 3). Interestingly, features supporting the presence of Eosinophil Extracellular Trap Cell Death (EETosis), i.e. nuclear rounding with loss of nuclear lobulation and rupture of plasma membrane of eosinophils, resulting in the release of extracellular granules, were found in one case (Fig. 4). Conclusions: Exhaustive processing of mucus plugs may disclose not only an abundance of eosinophils, but also the presence of ductal cells with eosinophilic infiltration and focal mucous metaplasia, reflecting the corresponding prominent histopathological features of ES. The potential involvement of EETosis in the pathophysiology of ES, as suggested by our preliminary findings, must be further explored.