The WHO classification of salivary gland tumours has increased significantly from nine histological types of epithelial tumors in the first edition (1972) to 36 in the current fifth edition (2022). This is largely because of the global accumulation of case data, advances in immunohistochemistry, and developments in molecular analysis techniques. However, the important and frequent histological types (e.g., Pleomorphic adenoma, Warthin tumor, Basal cell adenoma/adenocarcinoma, Mucoepidermoid carcinoma, Adenoid cystic carcinoma, Acinic cell carcinoma, Salivary duct carcinoma and Epithelial-myoepithelial carcinoma) described in the second edition (1991) have not changed, and various differential diagnoses among them remain challenging in routine practice. 　Although the recent elucidation of tumorspecific gene mutations has opened the door to new molecular targeted therapies and brought about major changes in clinicians (i.e., antiandrogen agents, trastuzumab, TRK inhibitors), the first step in a pathological diagnosis is still to interpret detailed histological findings and perform appropriate immunostaining. This article describes the evolution of the WHO classifications and the main diagnostic points in the major tumor groups, and provides an overview of the new tumor entities adopted in the current classifications. Furthermore, I outlined the current status of new therapeutic strategies based on specific molecular pathological findings.

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Saliva is functional water that affects the entire body. The author has been focusing on the functionality of saliva and has been proposing a new concept of saliva “quality” for more than 10 years. Saliva should then be viewed in terms of both quantity and quality. The author found that expression of the brain-derived neurotrophic factor BDNF is induced in salivary glands during stress. Furthermore, they found that salivary gland BDNF increases plasma BDNF levels via the oral floor region. Salivary gland-derived plasma BDNF may mildly increase BDNF levels in brain tissue and activate hippocampal TrkB receptors, thereby enhancing GABA production and contributing to the maintenance of hippocampal neuronal function from stress. Salivary glands and the brain are also in close proximity as blood flow-mediated root. The results of this study have led us to infer the existence of a salivary gland-brain correlation and have demonstrated new possibilities for the salivary glands. Now, salivary BDNF research, which taught us that salivary components are important for health, has develop a new health concept called “saliva care” and is advancing into a new social activity that contributes to the health of the public.

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