Pathology of Severe Influenza Virus Pneumonia: What Is the Importance of Alveolar Mouths?

Alveolar mouths (AMs) are very important points for the formation of Masson bodies (MBs) and hyaline membranes (HMs), which are considered serious complications of influenza virus pneumonia. MBs arise by injury, caused by influenza virus infection of AMs, which cover the epithelial and endothelial cells of AMs. Resulting exudates of AMs, mesenchymal cells, fibroblasts, and myofibroblasts proliferate, forming polyp-like MBs which protrude into air spaces. These structures are very sensitive to steroid therapy and are absorbed rapidly after steroid administration. However, if the MBs contain fibrin, as seen in acute fibrinous organizing pneumonia (AFOP), and myofibroblast proliferation, absorbed MBs remain in the septal and luminal spaces as pulmonary fibrosis. Massive MBs cause serious disturbance to respiratory function in peripheral airways. In HM formation, following injury to the epithelial cells of AMs irregular shaped fluffy fragmented substances form at AMs, becoming larger and flat in shape and forming membranous HM structures that disturb peripheral gas exchange. These HMs are immunopositive for cytokeratins, epithelial membrane antigen, KL-6, surfactant protein A, and Factor VIII-related antigens, but never fibrin. Following HM and MB formation, peripheral airways including alveolar orifices, such as respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli lose their gas-exchange capacity. Moreover, HMs form rapidly at AMs in the structurally retained pulmonary parenchyma, leading to acute respiratory insufficiency and numerous associating MBs in the peripheral airways.