Melanoma in children: A systematic review and individual patient meta‐analysis

Abstract

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross‐checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient‐level meta‐analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma‐specific survival (MSS) and progression‐free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de‐novo (DNM) and acquired or congenital nevus‐associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus‐associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over‐diagnosed as melanoma in childhood.

Pembrolizumab Versus High-Dose Interferon-α2b as Adjuvant Therapy for Pediatric Melanoma: A Retrospective Study

“…Distinct from melanoma in adults, spitzoid melanoma is one of the most common histologic subtypes in pediatric patients with melanoma. Interestingly, a recent meta-analysis including 1002 patients with melanoma have demonstrated that spitzoid melanoma with higher occurrence in children younger than 10 years harbors higher Breslow thickness and more propensity to nodal metastasis than non-spitzoid melanomas, but shows a more indolent biological behavior and a better prognosis [ 7 ]. Additionally, nevus-associated melanoma is more frequently observed in children than in adults, as a higher number of pediatric melanomas are associated with congenital nevi in younger patients.…”

Deconvoluted methylation profiles discriminate between closely related melanocytic nevi

“…Malignant transformation of any nevus is rare; however, a quarter of all superficial spreading melanomas (SSM) originate from a pre-existing AMN (Pampena et al 2023). In contrast, multiple medium to giant CMN are associated with significantly increased risk for prepubertal melanoma, particularly nodular (NM) but also extracutaneous, in direct proportion to the size and number of congenital lesions.…”

Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma

“…However, the incidence increases significantly in adolescents and reaches about 10 times the incidence of children in the age group of 15–19 years (Ferrari et al., 2019; Strouse et al., 2005). Most pediatric melanomas have a rather benign course, but there are also fatal outcomes in this age group (Pampena et al., 2023). The prognosis differs significantly between the subtypes of pediatric melanoma.…”