Abstract:

Epidermodysplasia verruciformis (EV) is a rare autosomal recessive hereditary condition associated with mutations in EVER1/2 genes. It is characterized by uncontrolled beta-HPV infections and increased risk of cutaneous squamous cell carcinoma. Acquired EV (AEV) occurs in patients with acquired immunodeficiencies, including organ transplant recipients and in the context of HIV infection. Here we report an AEV in a 27-year-old African American female with congenital HIV who had hundreds of 2-4 mm disseminated circular depigmented spots on her face, neck, upper thighs, and scattered on the rest of her body since her teens. A biopsy of one of the skin lesions showed epidermal acanthosis and papillomatosis with superficial keratinocytes exhibiting conspicuous viral cytopathic changes including enlarged nuclei, ample basophilic cytoplasm, and perinuclear halos. HPV-5 was detected using RNA in situ hybridization (RNAscope). The latter confirmed the abundant expression of HPV-5 RNA in areas histologically displaying epidermal hyperplasia and viral cytopathic changes, but not in the histologically unremarkable epidermis. The upper portion of the epidermis was predominantly involved. The biology of AEV in humans has recently gained more scientific interest. However, the studies of AEV predominantly utilize PCR-based nucleic acid detection assays which are limited by possible contamination by beta-HPVs that are ubiquitous on the skin surface of healthy individuals. Introduction of in-situ hybridization methods, such as RNAscope implemented here, allows for correlation between histomorphology and sensitive studies of nucleic acid detection. This offers means for a reliable virus detection, insight in viral compartmelization and may eliminate some confounding factors such as contamination. Our report convincingly links HPV-5 with AEV pathogenesis in humans. It also illustrates the utility of RNA in-situ hybridization methods in studying cutaneous diseases driven by beta-HPVs.

Financial Disclosure:
No current or relevant financial relationships exist.

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Kate Yu, MD, PhD