Immune dysregulation in thymoma: a potential mechanistic link to secondary lung cancer-a case report

Thymoma is a rare mediastinal neoplasm derived from thymic epithelial cells and is frequently associated with paraneoplastic autoimmune syndromes. Beyond these classical manifestations, thymomas can induce chronic systemic inflammation through impaired central tolerance, cytokine release, and immune dysregulation. This inflammatory microenvironment has been increasingly recognized as a potential contributor to secondary malignancies, although reports remain scarce.

We report a 71-year-old male with a significant smoking history who was diagnosed with non-small cell lung carcinoma (NSCLC), adenocarcinoma subtype, harboring an ERBB2 mutation and programmed death ligand 1 (PD-L1) expression of 0%. Staging studies revealed a small anterior mediastinal mass initially interpreted as a metastatic lesion from NSCLC. However, biopsy performed for staging purposes demonstrated type A thymoma. Histology demonstrated spindle-shaped epithelial cells (AE1/AE3⁺, p40⁺) within a background rich in CD3⁺ T-cells, terminal deoxynucleotidyl transferase (TdT)⁺ and CD1a⁺ immature thymocytes, and CD20⁺ B-cell aggregates. The patient developed spontaneous acute pericarditis with elevated inflammatory markers, while infectious and autoimmune causes were excluded. Flow cytometry and T-cell receptor (TCR) gene rearrangement studies were negative, indicating unexplained inflammation in the context of thymoma. We hypothesize that thymoma-associated immune dysregulation contributed to lung carcinogenesis through cytokine-driven inflammation and impaired autoimmune regulator (AIRE)-mediated central tolerance, leading to reduced tumor immunosurveillance. Prior reports describing elevated pro-inflammatory cytokines in thymic lesions and lung cancer support the concept of a paracrine inflammatory niche.

This case highlights a potential mechanistic link between thymic-associated immune dysregulation, chronic inflammation, and secondary malignancies. Recognition of this relationship is important for clinical management, long-term surveillance, and therapeutic decision-making in patients with thymoma. Future studies are warranted to further define the oncogenic consequences of thymic dysfunction and its implications for cancer development.