A Rare Case of Extramammary Paget Disease With Concurrent Herpes Simplex Virus Infection: Three-Color Immunohistochemical Analysis for Re-Evaluating Previous Hypotheses.

The coexistence of extramammary Paget disease and clinically apparent herpes simplex virus (HSV) infection is extremely uncommon, with only two cases previously described in detail. Herein, we present the case of an elderly woman with an extensive vulvar lesion showing concurrent extramammary Paget disease and HSV infection. Triple immunohistochemical staining for cytokeratin 7, cytokeratin 10, and HSV antigen was performed to re-evaluate the hypothesis that HSV-mediated fusion between Paget cells and keratinocytes contributes to multinucleated giant cell formation. HSV antigen was detected in both Paget cells and keratinocytes. HSV-positive multinucleated giant cells displayed a cytoplasmic staining pattern similar to that of keratinocytes, whereas no Paget cell-like cytoplasmic staining pattern was observed. These findings indicate that HSV can directly infect Paget cells and that the multinucleated giant cells in this case were of keratinocytic origin. No definitive evidence of cell fusion-either among Paget cells or between Paget cells and keratinocytes-was observed in the examined sections. However, the possibility of rare fusion events in unexamined tissue cannot be entirely excluded.