Influence of follow-up time on outcome of children and adolescents with atypical Spitz tumor/Spitz melanoma (AST/SM): Results from the MACMEL registry.

Abstract

e21558 Background: Pediatric melanoma is a rare and challenging diagnosis, requiring an integrated clinicopathologic and genomic approach to optimize diagnosis and clinical care. The Molecular Analysis of Childhood Melanocytic Tumors (MACMEL) registry (Pappo A Cancer. 2021 Oct 15;127(20):3825-3831) was developed to better characterize pediatric melanocytic lesions by including clinical information, central pathology review, and genomic analysis. The AST/SM subtype of melanocytic lesions often affects younger patients, have a high incidence of nodal involvement, and are genomically characterized by copy number aberrations and kinase fusions. Methods: A review of the MACMEL registry data for patients with AST/SM enrolled from May 2016 to December 2022. Patient data included demographics (age, sex, ethnicity), anatomic location of lesion, sentinel node involvement, AJCC staging, genomic and germline findings, therapy, and disease outcomes. Results: We identified 60 patients with AST (n=17) and SM (n=43). 28 patients had stage III disease and 16 had stage IIIC disease. There were 38 females, and 22 males. The most common primary sites were the extremities and the most common gene rearrangements included MAP3K8 (n= 10) and ALK (n= 12). Other genomic alterations identified included kinase fusions NTRK, ROS1, BRAF, FLOT2-ARAF, RAC1, BRIP1, SDHAF2, ATM, GPNMB-ERBB2, and CDKN2B. None of the 55 patients that underwent TERT promoter analysis had a mutation. Adjuvant treatment was given to 8 patients (interferon 3, pembrolizumab 4, larotrectinib 1). The median follow-up time for the cohort is 3.1 years, with 57 patients alive with no evidence of disease. 1 patient had a local relapse treated with wide local excision and is currently alive with no evidence of disease. 3 patients were lost to follow up. Event free survival (EFS) for the cohort is 98% and overall survival (OS) is 100%. Conclusions: Patients with AST/SM comprise the largest subtype of melanocytic lesions enrolled on the MACMEL registry and have an excellent clinical outcome. This supports our previous observations that patients with AST/SM who lack TERT promoter mutations may be able to be managed conservatively and that an integrated diagnostic approach incorporating genomic information is vital for optimal diagnosis and clinical management. [Table: see text]