Abstract

Case presentation: A 74-year-old man presented with a rapidly enlarging, irregular, 14cm black plaque on the left shoulder with satellitosis. Initial biopsy showed invasive malignant melanoma with multifocal dermal nests, focal epidermal attachment and foci of lymphovascular invasion. Systemic immunotherapy was used due to the large lesional area, beginning with immune checkpoint inhibitor Pembrolizumab and followed by modified oncolytic herpesvirus Talimogene Laherparepvec (TVEC). Physical examination after 6 months showed limited interval fading and decreased lesion size. Multiple scouting biopsies showed extensive pigment incontinence and numerous melanophages in an inflammatory background rich in plasma cells, but no residual melanoma cells, consistent with complete regression in the sampled areas. Discussion: TVEC is an innovative therapy utilizing a genetically engineered, live oncolytic herpes simplex virus 1 approved for managing unresectable melanoma. This injectable immunotherapy exerts antitumor effect by enhancing antigen presentation, T-cell priming, and direct lysis of melanoma cells. TVEC has intriguingly demonstrated an association with a distinctive histological profile characterized by a robust inflammatory infiltrate prominently enriched with plasma cells, as well as pronounced melanin pigment incontinence that has been reported to interfere with the clinical evaluation of disease response. This case shows the complete histological regression of melanoma despite pronounced melanin pigment incontinence and dermal melanophages physically mimicking residual disease. This case reinforces the critical role of scouting skin biopsy in evaluating response to TVEC. Furthermore, the inflammatory pattern associated with this case underscores the potential immunomodulatory effects of TVEC therapy, warranting further investigation into its underlying mechanisms and clinical implications.