Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers

Abstract

Background: Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness.

Methods: Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided.

Results: In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis).

Conclusions: T1 NM (compared with 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.

Figure 1.

Percentage of melanomas by nodular melanoma (NM) vs superficial spreading melanoma (SSM) histological subtype for increasing Breslow thickness by decimal point. A) In T1 melanomas. B) In T1 or T2 melanomas.

Figure 2.

Kaplan–Meier plots for melanoma-specific survival (MSS) rates for nodular melanoma (NM) compared with superficial spreading melanoma (SSM) for localized melanomas. A) In T1 cases: statistically significantly worse MSS for NM vs SSM (P = .002). B) In T2 cases (P = .29). C) In T3 cases (P = .12). D) In T4 cases (P = .66). P values were calculated using a two-sided log-rank test. Shaded areas indicate 95% confidence intervals. Vertical bold-dashed line indicates 5-year rates.