Detection of multinucleated giant cells in differentiated keratinocytes with herpes simplex virus and varicella zoster virus infections by modified Tzanck smear method

Herpes simplex virus (HSV) and varicella zoster virus (VZV) infections induce the formation of intraepidermal vesicles containing acantholytic cells and multinucleated giant cells in the skin. The Tzanck smear is most commonly used to diagnose cutaneous herpetic infections, but it leads to many false‐positive and ‐negative results. This study aimed at establishing a method detecting much larger multinucleated giant cells using the Tzanck smear because these cells characterize the viral cytopathic effect in skin infections. Morphological changes were analyzed among several layers of keratinocytes with HSV‐ or VZV‐related cutaneous lesions, clinically and in vitro. We compared the sensitivity of the Tzanck smear to detect large acantholytic cells using both the removed roof tissue part (our approach) and the floor of the lesion (conventional approach) of a fresh vesicle. Large acantholytic cells were detected 2.0‐times more frequently in the removed roof tissue part of the vesicle than in the floor of the lesion. Round cells were much larger in the removed roof tissue part of the vesicle corresponding to the granular or prickle layer of the epidermis than in its floor of the lesion corresponding to the basal or prickle layer with the Tzanck smear. Differentiated cultured keratinocytes formed multinucleated giant cells by cell‐to‐cell fusion with resolution of cell membrane with VZV infection. Differentiated keratinocytes promote multinucleated giant cell formation by cell‐to‐cell fusion with HSV‐1 or VZV infection. To increase the sensitivity, the Tzanck smear should be prepared from the removed roof tissue part of a fresh vesicle to detect multinucleated giant cells in herpetic infections.