{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T18:59:37Z","timestamp":1785265177793,"version":"3.55.0"},"reference-count":96,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"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>Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good\u2019s syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.<\/jats:p>","DOI":"10.3390\/cancers18050747","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:58:03Z","timestamp":1772114283000},"page":"747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-5179","authenticated-orcid":false,"given":"Matthew","family":"Abikenari","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshav","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, 300 Pasteur Dr. Lane Research Building, L200, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-5317","authenticated-orcid":false,"given":"Vratko","family":"Himic","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-1474","authenticated-orcid":false,"given":"George","family":"Nageeb","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7052-9906","authenticated-orcid":false,"given":"James","family":"Poe","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Joy","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, 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