Early Stages of Hyaline Membrane Formation Detected in Alveolar Mouths in Diffuse Alveolar-Damage-Associated Diseases: A Detailed Immunohistochemical Study.

To study the early stages of hyaline membrane (HM) formation, diffuse alveolar damage (DAD) was thoroughly investigated using immunohistochemical methods in 15 autopsy cases, which consisted of various types of interstitial pneumonias and pulmonary diseases derived from nonmalignant or malignant diseases. Alveolar mouths (AMs) that were presumed to be normal were ultrastructurally examined in detail, by using pulmonary tissues in the pneumothorax. It is interesting to note that during the initial stages of HM formation in AMs, fragmented eosinophilic masses were closely attached to AMs as irregular fragments or by a cap-like structure. The ultrastructure revealed some distance between the capillary spaces and surface epithelium of the AMs, indicating that the epithelial cells at the AMs might be often easily damaged even by minor stimuli; they can be considered as "locus minoris resistentiae." HMs were found to be formed initially at the site of AMs derived from fragmented eosinophilic masses in not only pulmonary but also extrapulmonary diseases, including both nonmalignant and malignant diseases. These irregular eosinophilic masses, representing the early shape of HMs, were immunohistochemically positive for the epithelial membrane antigens, namely, surfactant protein A and factor VIII antigen, and occasionally for KL-6 and cytokeratins. These results suggested that fragmented irregular masses represent the initial phase of HM formation. Five of 15 cases were focally negative for KL-6 at the initial irregular mass of HMs. Because KL-6 is one of the fundamental components of pulmonary surface elements, it needs to be studied further by detailed clinicopathological examination.