Perspective on thymectomy in adults

Kooshesh and colleagues, in their recent study (1), as well as a supporting editorial (2), have put forth the notion that surgical removal of the thymus from adults may increase overall mortality, the risk of cancer, and autoimmune diseases. They argue against total thymectomy whenever possible. My presentation during International Thymic Malignancy Interest Group (ITMIG) 2023 provided a counterargument to this sweeping conclusion. I believe that such a bold statement does a disservice to patients, surgeons, and physicians who may be considering procedures that involve thymus removal.

During fetal development and the first year of life, the thymus plays a pivotal role as the site where T cells mature and learn to distinguish between self-antigens and foreign invaders, such as bacteria and cancer cells. The thymus is highly metabolically active during this period, but over its natural lifespan, it begins to involute, having fulfilled its primary function by the first year of life (3). As Kooshesh et al. point out, for decades it was believed that thymic atrophy had no significant consequences. However, it has become increasingly clear that thymic atrophy may be linked to the broader phenomenon of immune senescence, which likely contributes to the age-related increase in susceptibility to infection, cancer, and possibly autoimmunity. Nevertheless, the crucial question remains: how significant is the impact of surgical thymus removal, especially in the context of therapeutic thymectomy?

The study in question is a retrospective, single-center evaluation, which inherently comes with certain limitations. Among the 1,146 subjects with matched controls who had undergone non-laparoscopic cardiac surgery, 871 had a cancerous or suspected thymic mass as the indication for surgery. This immediately raises questions about potential underlying genetic predispositions to future cancers, which cannot be adjusted for in the control population. Approximately 100 patients underwent therapeutic thymectomy for myasthenia gravis, a population known to have higher rates of autoimmune diseases and be treated with immunosuppressives, which increase the risk of infection and neoplasia (4). Consequently, they might exhibit biased results, not necessarily because of thymus removal. The indications for thymectomy included 183 cases of parathyroidectomy and 63 indeterminate cases. Notably, there is no assessment of the extent of thymectomy. Even when a surgeon aims for a “complete” thymectomy, this is seldom achieved due to the diffuse nature of the thymus, which extends across the mediastinum and up into the neck (5). Another methodological limitation is the reliance on the Mass General Brigham Research Registry (rc.partners.org), an excellent resource, but one that relies on electronic health record entries, thus inherently having limitations in data quality (6).

One significant concern is that the conclusions drawn from this study may discourage physicians and myasthenia gravis patients from considering thymectomy. Thymectomy for acetylcholine receptor antibody-positive myasthenia gravis has been shown to reduce disease severity (7). Previous studies of myasthenia gravis patients who underwent thymectomy did not reveal an increased risk of cancer (8-10). It is undeniable that patients with a thymoma, regardless of whether they have myasthenia gravis, should have the tumor removed. Furthermore, the removal of the surrounding thymic tissue may reduce the risk of tumor recurrence. Additionally, since the immune reaction to the tumor is triggered by the immune response and does not originate in the tumor itself, thymectomy has the potential to limit the development or reduce the severity of autoimmune diseases.

In conclusion, Kooshesh et al. conducted an intriguing study, but its findings do not warrant a recommendation to change current surgical practice. It is prudent to acknowledge that if one does not need to remove the thymus or any organ, then it should not be removed without due consideration of the potential risks and benefits.

Acknowledgments

Funding: This work was supported by NIH grant U54NS115054.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Malgorzata Szolkowska, Chul Kim, Mohammad Ashraghi, and Claudio Silva) for “The Series Dedicated to the 13th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2023)” published in Mediastinum. The article has undergone external peer review.

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-23-59/prf

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-23-59/coif). “The Series Dedicated to the 13th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2023)” was commissioned by the editorial office without any funding or sponsorship. H.J.K. is a principal investigator for the Rare Disease Network, MGNet supported by NIH grant U54NS115054 and a consultant for R43NS12432. He receives grants from Roche, UCB, and Takeda as site investigator. He is a consultant for Mimivax, Roche Pharma, Takeda, Cabaletta Bio, UCB Pharmaceuticals, EMD Serono, Ono Pharmaceuticals, Gilde Healthcare, Admirix, Inc., ECoR1 and Canopy. He received support from UCB for attending the Physician Education Meeting. He reports Stock options of Mimivax. Argenix provides an unrestricted educational grant to George Washington University. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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