Myasthenia gravis: immunohistological heterogeneity in microenvironmental organization of hyperplastic and neoplastic thymuses suggesting different mechanisms of tolerance breakdown

Abstract

Four samples of thymoma obtained from patients affected by myasthenia gravis have been immunohistologically analysed on cryostat sections using a panel of antisera and monoclonal antibodies specific for antigens which define different stages of intrathymic lymphocyte differentiation and antigens specific for different types of thymic epithelial cells (cortical, medullary). When the thymoma samples were compared to age-matched normal thymuses and hyperplastic thymuses obtained from patients with myasthenia gravis some evident microenvironmental differences could be demonstrated using these reagents. In all the thymoma samples in fact the neoplastic lobules appeared as grossly enlarged cortical-type areas, formed by accumulations of T lymphocytes exhibiting the cortical immature phenotype (TdT+, T6+, etc.) within a network of putatively neoplastic epithelial cells characterized by cortical phenotype as defined by reactivity with various monoclonal antibodies (RFD4-, MR3+). These 'cortical' epithelia showed some abnormal features such as lack or irregular distribution of HLA-DR and enhanced keratin expression. Small areas of 'medullary' differentiation could be observed in 3/4 thymoma samples. In thymic hyperplasia, on the other hand, the cortical areas appeared somewhat compressed (but comparable to those observed in normal age-matched samples) by enlarged medullary areas. The expansion of medullary areas was due to the infiltration of 'peripheral' lymphoid tissue intruding through the extraparenchymal zone and forming organized B and T areas. These observations are discussed in the light of the clinical heterogeneity observed in myasthenia gravis.