Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis.

Abstract

Non-neoplastic thymuses from 20 patients with myasthenia gravis (MG) have been studied by routine stains on paraffin sections and by immunohistological methods on frozen sections using a panel of monoclonal antibodies against thymic epithelial cells, macrophages/reticulum cells, lymphoid cells and myoid cells. Three types of thymic histology in MG were distinguished: (1) thymitis with lymphoid follicular hyperplasia (11 cases), (2) thymitis with diffuse B-cell infiltration (5 cases) and (3) thymic atrophy (4 cases). Thymitis was more common in younger females and thymic atrophy in older patients. Both types of thymitis were associated with conspicuous structural disturbance of the thymic perivascular space (PVS) and medulla, characterized by a distinct enlargement of the PVS and disruption of the epithelium and reticulin fibre network at the medullary boundary, leading to fusion of the two compartments. The PVS and medulla contained a striking B-cell infiltration. Large well-developed germinal centers (GCs), showing the same cellular organization as in the peripheral lymphatic system, occurred in thymitis with lymphoid follicular hyperplasia, whereas thymitis with diffuse B-cell infiltration merely exhibited a few tiny lymphoid follicles, which could be demonstrated only by immunostaining of dendritic reticulum cells. In thymic atrophy a diffuse B-cell infiltration of the PVS and the medulla was also observed, but only minor alterations of the epithelial framework were seen. There was an increased number of interdigitating reticulum cells with variable expression of the T-6 antigen in all the thymuses examined, indicating an immune stimulation of the intrathymic T-cells. Myoid cells, the supposed target of the intrathymic immune reaction in MG, were found to be less frequent in thymic atrophy than in thymitis. This variable number of myoid cells may explain the different grades of immune stimulation and different types of histology seen in the thymus in MG.