Special subtypes of pulmonary adenocarcinomas indicated by different tumor cell HLA-expression and stromal infiltrates. A light, electron microscopic and immunohistologic study.

A total of 31 human peripheral adenocarcinomas (AC) of the lung were subclassified by light and electron microscopy according to their phenotypic characteristics. The expression of HLA-A,B,C and HLA-DR on tumor cells, and the degree of subclassified mononuclear cell infiltration were determined using immunohistologic and morphometric methods. The study shows that pulmonary AC can be subdivided in two main types with different properties. The first type is characterized by mucin production comparable to that of bronchial goblet cells. These mucinous AC of type I show nearly no expression of HLA-DR; the tumor volume fraction with HLA-A,B,C expression is greatest in highly differentiated AC I, and decreases significantly with lower grades of differentiation. The AC of type II, possibly originating from the bronchioloalveolar transitional zone, show properties of Clara cells and of type II-pneumocytes by light and electron microscopy. These features include apically located electron-dense granules and lamellar bodies occurring often simultaneously. Both groups of HLA-antigens, HLA-A,B,C and HLA-DR, are homogeneously distributed in a similar phenotypic fashion to Clara cells and pneumocytes II of the normal lung. The significant differences in mononuclear cell infiltration between the two tumor types are possibly induced by the different HLA-DR expression, which have not been seen in AC from other sites. In AC II with homogeneous HLA-DR expression in the tumor epithelium, the numbers of tumor-infiltrating Langerhans cells, and T- and B-lymphocytes are significantly higher than in AC I, possibly indicating better host immunologic defense mechanisms against these tumors.