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Epidermodysplasia Verruciformis

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Skin biopsies from epidermodysplasia verruciformis (EV) lesions show acanthosis, hyperkeratosis, and hypergranulosis. The upper epidermis shows large keratinocytes arranged in clusters or columns. There is perinuclear vacuolization, keratohyaline granules, and a striking blue-gray cytoplasm.

Advanced lesions show dysplastic changes consisting of nuclear enlargement and hyperchromasia and disorderly maturation. The changes progress to in-situ carcinoma and eventually to invasive carcinoma (30-50% of cases).

Most cases of EV contain loss-of-function mutations in one of the two adjacent transmembrane channel (TMC) genes termed TMC6 (encoding EVER1) and TMC8 (EVER2). They have been mapped to 17q25.3 locus. The EVER1 and EVER2 proteins form a complex with calcium- and integrin binding protein (CIB1 protein). The disruption of CIB1-EVER1-EVER2-dependent immunity underlies increased susceptibility to HPV skin infections caused by beta genus.

Image courtesy of: Silvija Gottesman, MD, New York, USA; used with permission.

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