Pemphigus and the odd man under the microscope

Pemphigus vulgaris is an autoimmune blistering disorder characterized by acantholysis and suprabasal blister formation. Multinucleated giant cells (MNGCs) on cytology are classically associated with herpetic infections and may lead to diagnostic confusion when encountered in vesiculobullous disorders. Their presence in pemphigus is uncommon and warrants careful clinicopathological correlation. This article also explores the complex relationship between pemphigus and herpetic infection. It sheds light on an exhaustive list of causes of multinucleate giant cells in dermatology. A 47-year-old male presented with vesicles and non-healing erosions involving the oral cavity, trunk, extremities, and crusted scalp plaques of 1-month duration. Clinically, pemphigus was suspected. Tzanck smear revealed acantholytic cells along with MNGCs showing nuclear molding, suggestive of herpetic infection. However, viral serology was negative, and there was no response to antiviral therapy. Histopathology demonstrated suprabasal acantholysis with blister formation, and direct immunofluorescence showed intercellular IgG and C3 deposition, confirming pemphigus vulgaris. Multinucleate giant cells, some of which may be diagnostic, are seen in a variety of dermatoses. These are most commonly seen in herpetic and varicella infections in vesicular disorders but have rarely been reported in pemphigus in the absence of viral co-infection. These may represent macrophage-derived giant cells engulfing acantholytic cells. Pemphigus and herpesvirus infections share a complex relationship, wherein they may coexist, mimic each other, or possibly share immunopathogenic mechanisms. The presence of MNGCs in Pemphigus vulgaris can mimic herpetic infection and pose a diagnostic challenge. Histopathology and immunofluorescence are essential for accurate diagnosis and to exclude viral co-infection.