IMPORTANCE Previous studies have reported that histopathologically
amelanotic melanoma is associated with poorer survival than pigmented
melanoma; however, small numbers of
amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare
melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented
melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary
melanomas centrally scored for histologic pigmentation from the Genes, Environment, and
Melanoma(GEM) Study, which enrolled incident cases of
melanoma diagnosed in 1998 through 2003 from international population-based
cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and
melanoma-specific survival of histologically amelanotic and pigmented
melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467
melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting
nevus were independently associated with
amelanotic melanoma (each P < .05).
Amelanotic melanoma was generally ofa higher American Joint Committee on
Cancer (AJCC)
tumor stage at diagnosis (odds ratios[
ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for
tumor stages between T1b and T3b and
ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented
melanoma. Hazard of death from
melanoma was higher for amelanotic than for pigmented
melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex, anatomic site, and study design variables, but survival did not differ once AJCC
tumor stage was also taken into account (HR, 0.8; 95%CI, 0.5-1.2)(P = .36).CONCLUSIONS AND RELEVANCE 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.