Does the Morphology of Cutaneous Melanoma Help to Explain the International Differences in Survival?

Results From 1,578,482 Adults Diagnosed During 2000-2014 in 59 Countries (CONCORD-3)

Veronica Di Carlo; Charles A. Stiller; Nora Eisemann; Andrea Bordoni; Melissa Matz; Maria P. Curado; Laetitia Daubisse-Marliac; Mikhail Valkov; Jean-Luc Bulliard; David Morrison; Chris Johnson; Fabio Girardi; Rafael Marcos-Gragera; Mario Šekerija; Siri Larønningen; Eunice Sirri; Michel P. Coleman; Claudia Allemani


The British Journal of Dermatology. 2022;187(3):364-38. 

In This Article

Abstract and Introduction


Background: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000–2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma.

Objectives: We aimed to assess whether the differences in morphology may explain global variation in survival.

Methods: Patients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722–8723, 8726–8727, 8730, 8740–8741, 8746, 8761, 8770–8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All-ages survival estimates were standardized using the International Cancer Survival Standard weights. We fitted a flexible parametric model to estimate the effect of morphology on the hazard of death.

Results: Worldwide, the proportion of nodular melanoma ranged between 7% and 13%. Acral lentiginous melanoma accounted for less than 2% of all registrations but was more common in Asia (6%) and Central and South America (7%). Overall, 36% of tumours were classified as superficial spreading melanoma. During 2010–2014, age-standardized 5-year net survival for superficial spreading melanoma was 95% or higher in Oceania, North America and most European countries, but was only 71% in Taiwan. Survival for acral lentiginous melanoma ranged between 66% and 95%. Nodular melanoma had the poorest prognosis in all countries. The multivariable analysis of data from registries with complete information on stage and morphology found that sex, age and stage at diagnosis only partially explain the higher risk of death for nodular and acral lentiginous subtypes.

Conclusions: This study provides the broadest picture of distribution and population-based survival trends for the main morphological subtypes of cutaneous melanoma in 59 countries. The poorer prognosis for nodular and acral lentiginous melanomas, more frequent in Asia and Latin America, suggests the need for health policies aimed at specific populations to improve awareness, early diagnosis and access to treatment.


The incidence of cutaneous melanoma has been rising steadily in most white populations over the past 50 years.[1,2] It is now one of the 10 most common malignancies in Oceania, North America and Europe, with age-standardized incidence rates in the range of 7.0–36.6 per 100 000 person-years. By contrast, melanoma is rare in populations of Asian and African origin, where incidence rates are in the range of 0.4–3.0 per 100 000 person-years.[3] The histopathological features of cutaneous melanoma vary markedly worldwide. The proportion of melanomas with the more aggressive acral lentiginous or nodular histological subtypes is higher in populations with predominantly dark skin than in populations with predominantly fair skin.[4,5]

The third cycle of the CONCORD programme for the global surveillance of cancer survival (CONCORD-3)[6] highlighted wide disparities in 5-year net survival from cutaneous melanoma, which was lower in Asian populations than in the rest of the world. Age-standardized 5-year net survival for adults (15–99 years) diagnosed during the period 2010–2014 was 90% or higher in the USA, Australia, New Zealand and most Nordic countries, but was 60% or lower in Ecuador, China, Korea, Singapore and Taiwan.

Stage at diagnosis is recognized as the most important predictor of survival.[7–10] Age at diagnosis is also a prognostic factor, and several studies have shown much higher survival for younger patients.[11–15] However, the prognostic role of morphology in cutaneous melanoma is controversial. Traditionally, melanomas of the skin have been classified into the following three fairly well-defined subgroups, characterized by different patterns of growth: superficial spreading and lentigo maligna melanoma, which is characterized by a long period of superficial growth; nodular melanoma, which is more likely to penetrate into the deeper layers of the skin if not removed; and acral lentiginous melanoma, which mostly develops on the extremities but displays similar biological behaviour to that of nodular melanoma.[16] Despite the advent of high-resolution genomics and other proposed approaches for the classification of melanocytic tumours, the diagnosis of the different subtypes should continue to be based on the pathologist's interpretation of the histology and how it fits into the World Health Organization (WHO) Classification of Tumours, commonly known as the WHO 'Blue Books'.[17] However, the morphological classification has not been considered useful for prognostic purposes because of the commonly held view that the clinical development of all melanomas is similar, whatever the histological subtype, spreading horizontally within the epidermis and then extending vertically into the dermis, and that they converge in their biological behaviour once they metastasize.[18]

In this study, we aimed to describe the histological distribution of cutaneous melanoma for adults diagnosed during 2000–2014 in the 59 countries that contributed data to CONCORD-3 and to produce the first international comparison of trends in population-based age-standardized 5-year net survival by morphological subtype. We also aimed to examine the role of morphological subtype in the prognosis of cutaneous melanoma.