Epidermolysis bullosa (EB) is classified into the three major subtypes depending on the level of skin cleavage within the epidermal keratinocyte or basement membrane zone. Tissue separation occurs within the intraepidermal cytoplasm of the basal keratinocyte, through the lamina lucida, or in sublamina densa regions of the basal lamina (basement membrane) in EB simplex, junctional EB, and dystrophic EB, respectively. Transmission electron microscopy (TEM) is an effective method for determining the level of tissue separation and hemidesmosome (HD) and anchoring fibril morphology if performed by experienced operators, and has proven to be a powerful technique for the diagnosis of new EB patients. Recent advances in genetic and immunofluorescence studies have enabled us to diagnose EB more easily and with greater accuracy. This contribution reviews TEM findings in the EB subtypes and discusses the importance of observations in the molecular morphology of HD and basement membrane associated structures.
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