Frank C. Detterbeck

There is increased recognition that some lung cancers arise from or are associated with air-filled cystic spaces. Recognition of precursors is important because these are often overlooked and because some of these cancers progress rapidly once a solid component develops. A systematic review suggests that such precursors typically appear as irregular air cysts; these should be distinguished from bullae and smooth round cysts with paper-thin walls that are often seen incidentally with increasing age. Such irregular cysts usually enlarge slowly before developing a ground glass or small solid component or becoming multiloculated. Such change warrants careful surveillance; continued progression of a solid component justifies intervention. Early intervention is associated with good outcomes; survival markedly diminishes if resection occurs when a more substantial solid component has developed.

Background: A recent study raised questions about health consequences of thymectomy in adults. International Thymic Malignancy Interest Group (ITMIG) members need a thorough understanding of this. Methods: The study hypothesis was that thymectomy leads to worse survival and increased subsequent cancer, autoimmune disease, and infection (due to immune compromise). The primary analysis compared patients undergoing thymectomy to matched controls undergoing cardiac surgery, with endpoints of survival, subsequent cancer, autoimmune disease, or infection. The secondary analysis aimed to correlate the primary findings with an increase in severity of subsequent cancers—by analyzing unmatched patient subsets (n=75) who developed cancer or autoimmune disease after thymectomy vs. cardiac surgery. A tertiary analysis assessed immune function markers in an unmatched subset in whom blood was available (n=19/22). Results: The primary analysis suggested that thymectomy was associated with worse survival and more cancers, but not autoimmune disease or infection. However, confidence in interpretation and attribution of the effect to thymectomy is weakened by questions regarding the comparator selection, matching process, the approach to confirmatory subset analyses and the time period when differences became manifest. The secondary analysis suggests that thymectomy is associated with more aggressive cancers and multiplicity of autoimmune diseases than the comparator cohort. However, the thymectomy and cardiac surgery cohorts were unmatched; differences in age and sex and ambiguities regarding endpoint definitions create uncertainly in interpretation and effect attribution. Interpretation of the tertiary analysis is hampered by the limited cohort of unmatched patients; however, evidence of diminished immune function was seen after thymectomy vs. controls, and in patients who developed cancer vs. those who didn’t. Conclusions: The NEJM study suggested that thymectomy may have health consequences, which is consistent with basic science data (reviewed separately) that immune compromise associated with thymic involution may be linked to the incidence of cancer, autoimmune disease and infections with increasing age. However, the questions regarding the structure of the NEJM study as discussed in this abstract leave uncertainties how clearly the observations can be attributed to thymectomy.