Epidermolytic hyperkeratosis may present as a solitary lesion (acanthoma), as in this case, as an incidental finding on histology, i.e. within a dysplastic nevus, or as a generalized phenomenon like in bullous congenital ichthyosiform erythroderma. There appears to be an association with KRT1 and KRT10 keratin defects. Although histologically characteristic, the differential diagnosis would also include viral warts.
The characteristic perinuclear clear cell change is evident in the upper stratum spinosum and granular layer. This vacuolization appears in association with large chunky keratohyaline granules. This "epidermolysis" does not involve the bland normal-appearing basal keratinocytes.