Severe oral cGVHD is characterized by increased infiltration in the epithelial layer and apoptosis of keratinocytes. (A) Oral chronic GVHD is classically characterized by “dyskeratotic” epithelial cells and mononuclear cell satellitosis (small arrow) and lichenoid infiltrate (large arrow) under the basement membrane (dotted line), hematoxylin and eosin [H&E] × 40). Apoptotic cells (green) closely associated with infiltrating CD45 cells (red) are increased in the keratinocyte layer of the patient with severe oral GVHD (B) but not in the control patient lacking oral cGVHD symptoms (C). Apoptosis within epithelial layer is limited to keratinocytes. Cells within epithelial layer expressing active (cleaved) caspase-3 (D, red) also express cytokeratin (E, cyan). (F) Overlay. Both apoptotic cells (G) and CD45 cells (H) are significantly increased in the patients with severe disease (n = 8, n = 16, and n = 11 for control, mild, and severe groups, respectively; *P < .01; error bars represent SEM).