Distinct clinicopathological and prognostic features of thin nodular primary melanomas: an international study from 17 centers.

Abstract

BACKGROUND\nNodular melanoma (NM) is more likely to be fatal compared to other melanoma subtypes, an effect attributed to its greater Breslow thickness.\n\n\nMETHODS\nClinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n\u2009=\u200915), USA and Australia between 2006 and 2015, were analyzed by multivariate logistic regression analysis, with emphasis in thin (T1 ≤ 1.0\u2009mm) melanomas. Cox analysis assessed melanoma-specific survival (MSS). All statistical tests were two-sided.\n\n\nRESULTS\nIn all, 20,132 melanomas (NM: 5,062, SSM: 15,070) were included. Compared to T1 SSM, T1\u2009NM was less likely to have regression (OR: 0.46, 95% CI: 0.29-0.72) or nevus remnants histologically (OR: 0.60, 95% CI: 0.42-0.85), and more likely to have mitoses (OR: 1.97, 95% CI: 1.33-2.93) and regional metastasis (OR: 1.77, 95% CI: 1.02-3.05). T1\u2009NM had a higher mitotic rate than T1 SSM (adjusted geometric mean 2.2 [95% CI:1.9-2.4] vs 1.6 [95% CI:1.5-1.7] per mm2, p\u2009<\u20090.001). Cox multivariate analysis showed a higher risk for melanoma-specific death for NM compared to SSM for T1 (HR: 2.10, 95% CI: 1.24-3.56) and T2 melanomas (HR: 1.30, 95% CI: 1.01-1.68), while after accounting for center heterogeneity, there was statistical significance only for T1 (HR: 2.20, 95% CI: 1.28-3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis).\n\n\nCONCLUSIONS\nT1\u2009NM (compared to T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.