Abstract

Spitzoid melanoma, subtype of melanoma, clinicopathologically resembles Spitz nevus, with differentiation based on morphology and molecular landscape. We present a 15-year-old male with metastatic Spitzoid melanoma progressing in a previously excised nevus diagnosed as Spitz nevus to illustrate potential pitfalls and the value of genomic confirmation. A nevus on his left cheek was removed by two resections due to positive margins, with a pathology consistent with inflamed compound Spitz nevus. Without regular follow-up, enlarged left cervical lymph nodes were found 2 years later, and pathology confirmed metastatic melanoma. Patient received neoadjuvant immunotherapy with trametinib and dabrafenib for 6 months followed by lymph node resection, with pathology revealing 2/24 nodes positive to melanoma. He then received another 6 months of this therapy without hypermetabolic lymphadenopathy by PET scan. After one-year follow-up, he was found to have numerous lymphadenopathies on left and right neck on PET scan. Initial biopsies showed reactive nodes, but subsequent biopsy identified metastatic melanoma with TMB of 24 muts/Mb including BRAF V600E, TP53 and TERT promoter mutation which defined the Spitzoid melanoma. Mutation pattern was found to be consistent with DNA mismatch repair deficiency mutation signature. PD-L1 expression in tumor cells was present (30%).  Pembrolizumab was started for one year and patient has had a complete remission with a close follow-up with repeated PET scan every 3 – 6 months. This case raises the awareness of the role of genetic testing in differentiation between Spitz melanocytic proliferation and melanoma with Spitzoid features (or Spitzoid melanoma) that requires close monitoring.