A gastric biopsy is performed on a patient with suspected graft-versus-host disease following bone marrow transplantation. The biopsy demonstrates many isolated dying epithelial cells in crypts showing fragmented, hyperchromatic nuclei and small discrete blebs containing both cytoplasm and nuclear fragments. The biopsy proves which of the following?

The changes described are those of apoptosis, which is a form of programmed cell death. Apoptosis can be seen in a variety of settings. In this case, it is occurring in the context of graft-versus-host disease, which is mediated by CD8+ and CD4+ cells. Apoptosis also occurs during embryogenesis, during hormone-dependent involution in the adult (eg, during menstruation), during rapid proliferation of cell populations (eg, intestinal crypt epithelia), and in the immune system (e.g., in developing thymus). It can also occur after duct obstruction in organs such as pancreas and during some viral diseases. The hallmark of this programmed method of cell death is the fragmentation of the cell with formation of cytoplasmic blebs and apoptotic bodies that are phagocytized by other healthy cells. Caseous necrosis, such as is seen in tuberculosis, shows necrotic, amorphous granular debris surrounded by a granulomatous response. Coagulative necrosis, such as is seen in myocardial infarction, shows coagulated, anuclear cell "ghosts." Gangrenous necrosis is a commonly used surgical term (eg, in diabetic feet) that does not have a precise pathologic counterpa.