Relationship between structure and T-lymphocyte maturation in human thymomas. Enzyme histochemical and...

Twenty-six human thymomas were studied in an attempt to correlate their morphological appearance with the type and degree of T-lymphocyte maturation, as determined by acid alpha-naphthyl-acetate esterase (ANAE) activity and immunological analysis. Four normal human thymuses were used for purposes of comparison. Two morphological patterns were identified in the thymomas. The distinction was based largely on similarities between the neoplastic epithelial cells and normal cortical and medullary epithelial cells, and on the relative proportions of epithelial cells and lymphocytes. By these criteria "medullary" and "cortical" patterns were identified. In several thymomas both patterns were present in the same tumor ("mixed-type pattern"), producing alternating dark cortical-like areas and lighter foci of medullary differentiation. A good correlation was found between the two patterns and the phenotype of the T-associated lymphoid component. ANAE activity, which was completely lacking in normal cortical thymocytes, was almost absent in the phenotypically immature T-cells of cortical-type thymomas. By contrast, in the medullary-type thymomas, T-cells showed immunological features in common with medullary thymocytes. This was characterized by strong ANAE activity in the majority of cells with a staining pattern corresponding to that of peripheral T-lymphocytes. In addition, most of the proliferating epithelial cells in medullary-type thymomas stained strongly with anti-cytokeratin and anti-epidermal-type keratin antisera. In the mixed-type thymomas the epithelial cell morphology and the immunohistochemical and enzymic features of the T-cells were found to be closely related to the respective cortical--or medullary-like areas. It was concluded that the various characteristics of normal thymic cortex and medulla studied are also present in thymomas. In particular, in medullar-type thymomas the presence of many of the features of normal thymic medulla, such as a squamous cell component, macrophages and interdigitating reticulum cells, may constitute a microenvironment which operates actively in T-cell education. This may account for the functional activities, characteristic of peripheral T-lymphocytes, which T-lymphocytes attain in these thymomas.