Controversies and consensus on immune function and long-term health risks following adult thymectomy: a comprehensive review of molecular mechanisms and real-world evidence

Objective To evaluate the long-term immunological, oncological, and clinical consequences of adult thymectomy by synthesizing recent basic, translational, and real-world clinical evidence. Background Historical surgical paradigms regarded the post-pubertal adult thymus as an immunologically redundant, fatty involuted organ, justifying routine “incidental” resection during cardiac procedures. A high-profile 2023 cohort study in The New England Journal of Medicine (NEJM) challenged this concept, reporting that adult thymectomy significantly increased 5-year all-cause mortality and cancer risk. Subsequent population-level studies (US SEER/NCDB, French PMSI) and deep-learning imaging cohorts have sparked debate, offering both corroborating and conflicting insights into adult thymic function. Methods and synthesis This review synthesizes cellular mechanisms (TREC dynamics, TCR repertoire contraction, senescence-associated T cells, Treg lineage stability) and endocrine factors (thymulin-mediated myeloid regulation) with clinical data stratified by age at surgery, indication, resection extent, and follow-up duration. Conclusions The adult thymus remains functionally active, exporting naïve T cells and humoral immunomodulators like thymulin that maintain peripheral immune tolerance and restrain inflammaging. Clinical evaluation must differentiate between incidental resection (which induces avoidable iatrogenic immunosenescence) and therapeutic resection (e.g., for thymic epithelial tumors or myasthenia gravis), where removing a diseased, immunosuppressive microenvironment can reduce secondary cancer risk. Partial thymectomy (PT) is emerging as an option to preserve immunocompetence when oncologically feasible.