Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland, mostly in the parotid gland. The epithelial cells constituting a tumor are characterized by the presence of mitochondria that undergo structural and functional changes, resulting in the development of oncocytes. In addition to containing epithelial cells, Warthin’s tumors contain abundant lymphocytes with lymph follicles (germinal centers) that are surrounded by epithelial cells. The pathogenesis of Warthin’s tumor is not fully understood, and several hypotheses have been proposed. The risk factors for the development of Warthin’s tumor, which predominantly occurs in males, include aging, smoking, and radiation exposure. Recently, it has been reported that chronic inflammation and aging cells promote the growth of Warthin’s tumor. Several reports regarding the origin of the tumor have suggested that (1) Warthin’s tumor is an IgG4-related disease, (2) epithelial cells that compose Warthin’s tumor accumulate mitochondria, and (3) Warthin’s tumor is a metaplastic lesion in the lymph nodes. It is possible that the pathogenesis of Warthin’s tumor includes mitochondrial metabolic abnormalities, accumulation of aged cells, chronic inflammation, and senescence-associated secretory phenotype (SASP). In this short review, we propose that DNA damage, metabolic dysfunction of mitochondria, senescent cells, SASP, human papillomavirus, and IgG4 may be involved in the development of Warthin’s tumor.
沃辛瘤是唾液腺中仅次于多形性腺瘤的第二常见肿瘤，主要发生于腮腺。构成肿瘤的上皮细胞特征在于存在经历结构和功能改变的线粒体，从而形成嗜酸细胞。除上皮细胞外，沃辛瘤还含有丰富的淋巴细胞及淋巴滤泡（生发中心），这些结构被上皮细胞包绕。沃辛瘤的发病机制尚未完全阐明，目前存在多种假说。该肿瘤好发于男性，其危险因素包括老龄化、吸烟及辐射暴露。近期研究表明，慢性炎症和衰老细胞可促进沃辛瘤生长。关于肿瘤起源的若干报道提出：（1）沃辛瘤属于IgG4相关性疾病；（2）构成沃辛瘤的上皮细胞存在线粒体蓄积；（3）沃辛瘤是淋巴结内的化生性病变。沃辛瘤的发病机制可能涉及线粒体代谢异常、衰老细胞累积、慢性炎症及衰老相关分泌表型（SASP）。本综述提出DNA损伤、线粒体代谢功能障碍、衰老细胞、SASP、人乳头瘤病毒和IgG4可能参与沃辛瘤的发生发展。
Pathogenesis of Warthin’s Tumor: Neoplastic or Non-Neoplastic?
肿瘤(癌症)患者之家