Author:
Dessinioti Clio,Dimou Niki,Geller Alan C,Stergiopoulou Aravella,Lo Serigne,Keim Ulrike,Gershenwald Jeffrey E,Haydu Lauren E,Ribero Simone,Quaglino Pietro,Puig Susana,Malvehy Josep,Kandolf-Sekulovic Lidija,Radevic Tatjana,Kaufmann Roland,Meister Laura,Nagore Eduardo,Traves Victor,Champsas Grigorios G,Plaka Mihaela,Dreno Brigitte,Varey Emilie,Ramirez David Moreno,Dummer Reinhard,Mangana Joanna,Hauschild Axel,Egberts Friederike,Peris Ketty,del Regno Laura,Forsea Ana-Maria,Zurac Sabina A,Vieira Ricardo,Brinca Ana,Zalaudek Iris,Deinlein Teresa,Linos Eleni,Evangelou Evangelos,Thompson John F,Scolyer Richard A,Garbe Claus,Stratigos Alexander J
Abstract
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.
Funder
Institute of Dermatologic Research and Education
European Union
Reinforcement of Postdoctoral Researchers
Human Resources Development Program, Education and Lifelong Learning
National Strategic Reference Framework
National Institutes of Health Specialized Program of Research Excellence
National Cancer Institute
National Institute on Aging
Melanoma Unit in Barcelona
MARATÓ de TV3 Foundation
Publisher
Oxford University Press (OUP)