Prognostic significance of novel histological parameters compared to Breslow thickness and tumour burden: An investigation.

Abstract

The clinical progression of cutaneous malignant melanoma (cMM) is primarily predicted using clinical and histopathological prognostic factors (Breslow thickness (BT), ulceration status and mitotic rate). However, BT is an absolute measurement and does not account for variations in skin anatomy nor does it convey accurate indication of the primary tumour burden. We evaluated whether the BT to dermal thickness (DT) ratio (BT/DT) or 3D assessments, such as estimated tumour volume (TV) are better prognosticators. A retrospective cohort study was conducted on 90 patients treated with cMM at a tertiary cancer centre between 1 January to 31 December 2005. Histological measurements of BT, DT, tumour width, and distance from the base of the tumour to the nearest subcutaneous fat (TF) were performed. TV was estimated using conical and hemispherical models. The collected data were analysed and prognostic significance for recurrence, metastasis and/or melanoma-specific death was assessed. The two novel parameters were not reliable independent prognostic indicators: BT/DT was non-significant on univariable analysis (p>0.05); although it reached nominal significance when modelled together with BT, this most likely reflects collinearity between the two measures. Furthermore, TF distance was also non-significant. However, adverse outcomes were observed in all cases where the tumour invaded into fat tissue (TF=0). In contrast, estimated tumour volume (tumour burden) was found to be statistically significant under both geometric models (p<0.001). Despite the crudeness of volume estimation, both models concordantly identified 3D tumour burden (TV) as prognostic, consistent with previous reports in the literature. BT/DT and TF distance were not significant prognostic indicators, although fat invasion indicated poorer outcomes. The study results suggest that intrinsic tumour biology and total burden outweigh the relative invasion depth within the dermis.