1. Amelanotic melanoma was typically diagnosed at a later AJCC tumor stage than pigmented melanoma.
2. After having accounted for Breslow depth, amelanotic melanoma was independently associated with histologic features that were suggestive of increased growth rate.
Evidence Rating Level: 2 (Good)
Study Rundown: Amelanotic melanoma poses a distinct challenge in diagnosis, as lack of pigment makes these tumors difficult to identify at early stages. Previous studies have indicated that poorer survival rate of amelanotic melanoma as compared to pigmented melanoma is due to advanced stage at diagnosis; however these studies had several limitations including limited number of cases and lack of centralized pathologic review. These authors sought to establish clinicopathologic features and survival of amelanotic vs. melanotic melanomas. Results corroborated that amelanotic melanoma was associated with advanced tumor stage at diagnosis, and increased mitoses on histology. The study was the only international study with an expansive cohort that utilized definition of tumor pigmentation by histopathology rather than clinical definition. Despite employing central pathologic review, the study was limited by the retrospective design and by moderate inter-rater agreement for histopathologic pigment. Future studies are needed to identify barriers to timely diagnosis and to improve diagnostic methods for these types of melanomas.
In-Depth [case-control study]: 2995 patients with a total of 3486 primary cutaneous melanomas from Australia, USA, Italy and Canada were selected from the Genes, Environment, and Melanoma Study Group. 8% of melanomas were amelanotic and the median follow-up time was 7.6 years. Melanomas with increased AJCC tumor stage were more likely to be amelanotic; the OR for stage T4b as compared to T1a was 29.1 (95% CI 15.5-54.9, P value <.001). Although there were increased death from melanoma in amelanotic melanoma as compared to pigmented melanomas (HR 2.0, 95% CI: 1.4-3.0), this difference was mitigated once AJCC tumor stage was accounted for. Other features associated with amelanotic melanoma were female sex, nodular subtype, increased Breslow thickness, presence of mitoses, solar elastosis, and lack of co-existing nevi (p<0.05). The independently aggressive histologic features associated with amelanotic melanoma suggest that apart from merely the challenge of early-diagnosis, amelanotic melanomas may also be more rapidly growing tumors.