Abstract:

Background: Primary scalp melanomas (PSM) are associated with worse outcomes compared to non-scalp counterparts of cutaneous head and neck melanoma (CHNM). Despite differences in stage at diagnosis, melanoma subtypes and anatomical variances, these features alone do not explain these outcomes. Mutational drivers including genotypes of BRAF differ according to anatomical site, age and degree of cumulative sun damage (CSD), but have not been characterised in the context of scalp melanoma. We sought to characterise mutation status and CSD associated with PSM, compared to non-scalp CHNM, to determine whether driver mutations account for the adverse outcomes. Methods: All patients with stage III/IV CHNM with molecular biomarker testing performed between 2000-2021 were identified from our institution database. Patients with multiple primary tumours, or those without records of histopathological variables were excluded from analysis. Results: Of all CHNM (n=395), 166 (42%) arose on the scalp. PSM had a higher incidence in males (79% male, p=0.0219), greater Breslow thickness (3.3mm vs 2.1mm, p<0.0001) and with higher mitotic rate (6/mm2 vs 4/mm2, p=0.0006) than their non-scalp CHNM counterparts. BRAF was mutated in equal frequency in PSM and non-scalp CHNM (X2 p=0.2472), but more commonly in superficial spreading (p=0.0002) and less in desmoplastic (p=0.0001) melanoma subtypes. High CSD correlated with a higher proportion of BRAF V600K mutations (vs V600E, p=0.0006), with a similar BRAF genotype profile seen in both scalp and non-scalp melanomas (p=0.5648). Conclusion: Provisional genotype analysis suggests that CSD contributes to the development of BRAF V600K mutations in scalp melanomas in a similar way to non-scalp sites. The study will further explore the prognostic effects of these molecular drivers, in an attempt to account for the more aggressive biological behaviour of these tumours.

Financial Disclosure:
No current or relevant financial relationships exist.

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Alison Potter, MBBS (Hons)