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 pathology review, or no adjustment for stage limit
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
Survival analysis with median follow-up of 7.6 years.
Setting
The Genes, Environment, and Melanoma study enrolled incident cases of
melanoma diagnosed in 1998-2003 from international population-based cancer
registries.
Participants
A total of 2,995 patients with 3,486 invasive primary melanomas
centrally scored for histologic pigmentation.
Main Outcomes and Measurements
Clinicopathologic predictors and melanoma-specific survival of
histologically amelanotic and pigmented melanoma were compared using
generalized estimating equations and Cox regression models,
respectively.
Results
Eight percent of melanomas (275 of 3,467) 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 co-existing nevus were independently associated
with amelanotic melanoma (each P < .05). Amelanotic
melanoma was generally of a higher American Joint Committee on Cancer (AJCC)
tumor stage at diagnosis (P for trend <.001) than
pigmented melanoma. Hazard of death from melanoma was higher for amelanotic
than pigmented melanoma [hazard ratio (HR), 2.0; 95%
confidence interval (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 biology of amelanotic melanoma are warranted.