Distribution of Ectopic Germinal Centers in Thymic Epithelial Tumors and Their Relationship With Thymic Involution

Ectopic germinal centers (GCs) are often formed in the thymus of patients with anti-acetylcholine receptor antibody (anti-AChR Ab)-positive thymic epithelial tumors (TETs) and are considered sites where B cells undergo affinity maturation to produce high-affinity anti-AChR Abs, contributing to the development of myasthenia gravis. To evaluate the clinical relevance of these ectopic GCs, we analyzed their distribution and associations with thymic involution and anti-AChR Ab titers using paraffin-embedded surgical specimens from 79 TET patients. Thymic involution was scored, and immunohistochemistry was performed to identify cells involved in GC formation. GCs were identified in 32 of the 79 cases. The anti-AChR Ab+ group had significantly higher frequencies of GCs in the residual thymus compared to the Ab- group. In all cases with GCs in the residual thymus, GCs were found both near the tumor and at distances greater than 1 cm from the tumor. Within the anti-AChR Ab+ group, GC+ patients were significantly younger and showed milder thymic involution than GC- patients. The number of GCs per unit area positively correlated with serum antibody titer. In Ab+ cases, AChR-α1 antigens were significantly more frequent in GC+ cases. In mildly involuted thymus, AChR antigens, antigen-presenting cells, and B cells were detected in the medulla, whereas these were rarely observed in severely involuted thymus. These findings suggest that GC formation occurs preferentially in a less involuted thymus and that surgical resection of at least the extent of a total thymectomy may be indicated in younger patients with anti-AChR Ab+ TETs.