BACKGROUND: Whereas the clinical manifestations and treatment of post-kala-azar dermal leishmaniasis (PKDL) have been adequately described before, the pathology received little attention, particularly the African form of PKDL which shows some clinical differences from the disease in India. Therefore, our aim was to characterize the pathology and the immunohistopathology in PKDL lesions and correlate the histopathological findings with the clinical features of the disease. METHODS: Biopsies of skin lesions were examined for histopathological changes in formalin-fixed tissues and for cell phenotypes and adhesion molecules by immunohistochemistry. RESULTS: The epidermis showed various changes in different combinations. The dermis was infiltrated by lymphocytes and macrophages, but plasma cells were scanty or absent. The majority of cells were CD3 T cells, with a preponderance of CD4 over CD8 cells. Degenerating basal keratinocytes expressed HLA-DR, ICAM-1 and Leishmania antigen and closely interacted with CD4 T cells. Regional lymph nodes showed hyperplasia of the B- and T-cell zones. Conclusions: The inflammatory reaction in PKDL lesions is in response to Leishmania parasites and/or antigen. The majority of cells are CD4 T cells. Degeneration of the basal keratinocytes is probably due to the action of cytotoxic CD4 T cells interacting with leishmania-expressing epidermal cells. Ismail A, Gadir AFA, Theander TG, Kharazmi A, El Hassan AM. Pathology of post-kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and ultrastructural study of skin lesions and draining lymph nodes.