After Adjustment for Stage at Diagnosis, No Difference Evident in Melanoma-Specific Mortality Between Amelanotic and Pigmented Melanomas
In a large international population-based study reported in JAMA Dermatology, Thomas et al found that increased risk of melanoma-related mortality for patients with amelanotic vs those with pigmented melanomas was no longer evident after adjustment for tumor stage at diagnosis.
The study involved 2,995 patients with 3,467 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma (GEM) Study, which included incident cases of melanoma diagnosed between 1998 and 2003 from international population-based registries.
Factors Associated With Amelanotic Melanoma
Among all melanomas, 275 (8%) were amelanotic. Female sex (fully adjusted odds ratio [OR] = 1.4), nodular (OR = 2.7) and unclassified or other (OR = 3.5) histologic subtypes, increased Breslow thickness (OR = 1.6–6.9), presence of mitoses (OR = 1.9), severe solar elastosis (OR = 2.0), and lack of coexisting nevus (OR = 0.6 for coexisting nevus) were independently associated with amelanotic melanoma (all P < .05). Amelanotic melanoma was of higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis, with adjusted ORs (P < .001 for trend) vs T1a of 2.9 for T1b, 3.5 and 11.1 for T2a and T2b, 9.0 and 4.6 for T3a and T3b, and 24.6 and 29.1 for T4a and T4b.
Mortality Risk
The risk of death from melanoma was higher for patients with amelanotic vs pigmented melanomas (hazard ratio [HR] = 2.0, P < .001) after adjustment for age, sex, anatomic site, and study design variables. However, after adjustment for AJCC stage at diagnosis, there was no significant difference in risk of death (HR = 0.8, P = .36).
The investigators concluded: “At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biological properties of amelanotic melanoma are warranted.”
Nancy E. Thomas, MD, PhD, of University of North Carolina, Chapel Hill, is the corresponding author for the JAMA Dermatology article.
The study was supported by the National Cancer Institute, National Institute of Environmental Health Sciences, University of Sydney Medical Foundation Program, and Michael Smith Foundation for Health Research Infrastructure.
The authors reported no conflicts of interest.
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