Germinal Centers in Thymus Act as Prognostic Factor in Thymoma-Associated Myasthenia Gravis

Ectopic germinal centers (GCs) were found to be a prognostic factor for poor outcomes for patients with thymoma-associated myasthenia gravis (TAMG), according to a new study published in the Journal of Neuroimmunology.¹ The pathogenesis of TAMG will require future studies to predict outcomes of treatment.

Weakness and fatigue of muscles are primary symptoms of MG, and cases with autoantibodies against the acetylcholine receptor (AChR-Ab) have been associated with thymic abnormalities. TAMG is a more severe version of MG and requires surgery to treat.² The main mechanisms of TAMG pathogenesis are established to be a loss of thymic tolerance and damage to the thymic environment, but the presence of GCs has also been linked to the pathogenesis of the condition due to their presence in TAMG vs MG. This study aimed to evaluate if clinical outcomes of MG after thymoma resection were associated with the presence of ectopic GCs in the thymus of patients diagnosed with TAMG.

Patients at Severance Hospital who had a thymectomy between January 2005 and October 2021 were eligible for the study. Patients who had thymic carcinoma or atypical thymoma, thymectomy before onset of MG, follow-up duration of less than 1 year, or insufficient thymic tissue slides were excluded from the study. Medical records were reviewed for clinical features of MG, date of onset, sex, treatment of MG, histological features of thymoma, and levels of serum AChR-Ab before and after the operation. Every patient with TAMG had an extended thymectomy.

There were 111 patients who had a thymectomy and were included in the study. A total of 62.2% had at least 1 GC, and 37.8% had none. Thymic lymphofollicular hyperplasia (TFH) grade 3 was found in 36.2% of those with at least 1 GC, and grade 2 was found in 23.2%. Patients with grade 2 or 3 TFH were in the GC-positive group.

The GC-positive group had a mean younger age at MG onset compared with the GC-negative group (41.4 [12.0] vs 47.9 [11.8] years). The GC-negative group had more patients on preoperative prednisolone treatment compared with the positive group (34.3% vs 9.8%). The AChR-Ab level was higher in the GC-positive group compared with the GC-negative group after the operation (10.3 [5.0] nmol/L vs 8.1 [3.9] nmol/L). Histology type B thymomas were also more common in the GC-positive group (90.2% vs 74.3%).

In patients who had not been treated with prednisolone before their thymectomy, minimal manifestation was significantly higher in the GC-negative group compared with the GC-positive group; pharmacological remission was not significantly different between the groups. The achievement of minimal manifestation was negatively associated with higher levels of AChR-Ab after operations, GC-positivity, and World Health Organization histology type B thymoma, which was confirmed with a multivariate Cox proportional hazards regression model, where GC-positivity was negatively associated with achieving minimal manifestation (HR, 0.479; 95% CI, 0.237-0.968).

There were some limitations to this study. There were many patients with MG who were excluded due to their tissue slides being insufficient for the analysis. The association between TFH grade and prognosis of MG was marginal and only analyzed semi-quantitatively. Treatment-related confounding could not be precisely quantified. Assessment of MG also relied on narrative documentation.

“This study observed that the presence of ectopic GCs in thymomas may be a prognostic factor for poor outcomes in patients with TAMG,” the authors concluded. “Knowledge concerning the risk factors for poor prognosis is needed for adequate clinical care and to plan for future treatment.”

References

1. Chung HY, Shin HY, Park HJ, Kim GJ, Kim SW. Germinal centers are associated with poor prognosis in patients with thymoma-associated myasthenia gravis. J Neuroimmunol. 2026;417:578926. doi:10.1016/j.jneuroim.2026.578926
2. Myasthenia gravis. Mayo Clinic. August 22, 2025. Accessed April 7, 2026. https://www.mayoclinic.org/diseases-conditions/myasthenia-gravis/symptoms-causes/syc-20352036