{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:27:38Z","timestamp":1791973658597,"version":"4.4.0"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Warthin\u2019s 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\u2019s tumors contain abundant lymphocytes with lymph follicles (germinal centers) that are surrounded by epithelial cells. The pathogenesis of Warthin\u2019s tumor is not fully understood, and several hypotheses have been proposed. The risk factors for the development of Warthin\u2019s 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\u2019s tumor. Several reports regarding the origin of the tumor have suggested that (1) Warthin\u2019s tumor is an IgG4-related disease, (2) epithelial cells that compose Warthin\u2019s tumor accumulate mitochondria, and (3) Warthin\u2019s tumor is a metaplastic lesion in the lymph nodes. It is possible that the pathogenesis of Warthin\u2019s 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\u2019s tumor.<\/jats:p>","DOI":"10.3390\/cancers16050912","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T11:31:21Z","timestamp":1708947081000},"page":"912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Pathogenesis of Warthin\u2019s Tumor: Neoplastic or Non-Neoplastic?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1164-9051","authenticated-orcid":false,"given":"Ryogo","family":"Aoki","sequence":"first","affiliation":[{"name":"Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-l Kashima-Cho, Gifu City 500-8513, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-1582","authenticated-orcid":false,"given":"Takuji","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-l Kashima-Cho, Gifu City 500-8513, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.oraloncology.2005.10.017","article-title":"Clinical features of cystadenolymphoma (Warthin\u2019s tumor) of the parotid gland: A retrospective comparative study of 96 cases","volume":"42","author":"Teymoortash","year":"2006","journal-title":"Oral Oncol."},{"key":"ref_2","first-page":"41","article-title":"Pathogenesis of Warthin\u2019s tumors","volume":"8","author":"Kuzenko","year":"2016","journal-title":"Interv. 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