Malignant Melanoma With Transdifferentiation Into a Ganglioneuroblastic Phenotype After Anti-PD-1 Therapy

The clinicopathologic spectrum of dedifferentiated, undifferentiated, and transdifferentiated melanoma occurring de novo or following systemic therapy is gaining recognition. Here, we present a patient with locally advanced cutaneous melanoma who received neoadjuvant anti-PD-1 therapy and whose post-treatment excisional pathology revealed transdifferentiation into a ganglioneuroblastic phenotype. This rare phenotype is hypothesized to be connected to melanoma's shared origin from pluripotent neural crest cells. This case report highlights the proposed pathogenic mechanisms underlying this transition after immune checkpoint therapy, including the pathways and factors that affect the tumor and its microenvironment.