Decreased melanogenic activity correlate with enhanced aggressiveness of cutaneous malignant melanoma

Abstract

Introduction. Cutaneous malignant melanoma exhibits marked heterogeneity in clinical behaviour and histopathologic appearance. Although tumour thickness, Clark level, and invasive growth patterns remain key prognostic indicators, the significance of melanocytic pigment synthesis remains incompletely defined. Amelanotic melanomas are often associated with delayed diagnosis and poorer outcomes. Loss of pigmentation may reflect melanocytic dedifferentiation, altered melanogenesis pathways, and enhanced invasive potential. The relationship between pigmentation status and established markers of aggressiveness has not been consistently quantified. This study investigates the relationship between pigmentation status and histopathologic indicators of tumour aggressiveness in superficial spreading melanoma. Materials and Methods. A retrospective analysis was performed on 47 cases of superficial spreading melanoma from the Oncology Institute of Chisinau. Histopathologic evaluation included tumour thickness, Clark level, ulceration, mitotic activity, microsatellitosis, pigmentation status, lymphovascular invasion, perineural invasion, and lymph node involvement. Pigmentation was assessed on hematoxylin–eosin–stained sections and classified as pigmented or non-pigmented. Correlations were analysed using Pearson correlation coefficients, with significance set at p ≤ 0.05. Results. The cohort included 47 patients (mean age 65.6 ± 12.15 years), comprising 24 females (51.1%) and 23 males (48.9%). Pigmented melanomas accounted for 34 cases (72.3%), while 13 cases (27.7%) were non-pigmented. Pigmentation status demonstrated statistically significant inverse correlations with several established histopathologic markers of tumour aggressiveness. A moderate negative correlation was observed between pigmentation and tumour thickness (r = −0.42, p = 0.0001), indicating that non-pigmented melanomas were associated with increased tumour thickness. Similarly, pigmentation was inversely correlated with Clark level (r = −0.38, p = 0.001). Pigmentation showed significant negative associations with both, lymphovascular invasion (r = −0.26, p = 0.04) and perineural invasion (r = −0.24, p = 0.05), suggesting a higher frequency of invasive features in nonpigmented tumours. No other parameters showed significant correlations. Conclusions. Loss of pigmentation in superficial spreading melanoma is associated with a more aggressive histopathologic profile, including greater tumour thickness, higher Clark level, and increased invasive features. Pigmentation status may serve as an additional prognostic indicator and warrants careful evaluation in routine histopathologic assessment.