ALM is the least frequent of the four major histologic subtypes of CMM overall; however, it is a higher percentage of total melanoma in people of color. ALM was first described in the late 1970's and not documented by SEER as a distinct melanoma histologic subtype until 1986. The distinct histologic and phenotypic characteristics of ALM, in conjunction with its higher proportion of melanoma subtypes in Blacks, Hispanics, and Asians, has fostered speculation that this histologic variant of melanoma might differ biologically from its counterparts. However, accurate assessment of ALM in the United States has been difficult because ALM accounts for such a small proportion of melanomas.23
This study is the largest population-based evaluation of ALM yet conducted. We provide new data, particularly in Hispanic Whites and Asian/Pacific Islanders, on current incidence and survival patterns in the United States.
The proportion of ALM among all melanoma subtypes was greatest in people of color, with Blacks having the highest percentage (36%). These results are in contrast to former studies showing that SSM was the most common histologic subtype for all racial groups, including Blacks.12,13
It is important to note that our study included all SEER registry areas, representing approximately 26% of the US population. We also include the latest data from the years 2004 and 2005. Zell et al showed trends for melanoma in the state of California from 1993-2003, representing ~12% of the US population.13
Cormier et al showed trends for melanoma in the SEER 11 registries from 1992-2002,12
representing ~14% of the US population.
The incidence of ALM in the United States has remained relatively steady over time, unlike CMM overall, where the incidence has been steadily increasing. During the 1970's, the incidence rate of CMM increased rapidly by about 6% per year.1
Since 1981, the rate of increase has slowed to 1 to 3% per year. The steady increase in CMM incidence is most likely due to increased ultraviolet radiation, even though increased surveillance, physician and patient education, and sun safety measures have dramatically slowed the rate of increase. Our study showed that the incidence of ALM increased slightly from 1.6 to 2.1 per 1,000,000 person years from 1992 to 2005. This increase is most likely a result of ALM being recognized as a separate histologic subtype of melanoma in the mid 1980's and represents an overall increase in diagnosis. The incidence rate for ALM was similar in Non-Hispanic Whites and Blacks, but statistically lower in Asian/Pacific Islanders. Interestingly, Hispanic Whites had statistically higher incidence rates of ALM. In a recent population-based study of invasive melanoma in Hispanics, Cockburn et al reported an increasing incidence rate of CMM overall in the Hispanic population of California.14
Given our results and the increasing rate of melanoma overall in Hispanic populations, education campaigns should also provide information on ALM, particularly because of its atypical locations.
Melanoma in people of color has been shown to have a predilection for acral locations, especially on plantar regions.7,12,24
This also appeared to be true in our study in which the most frequent locations for ALM were on the lower limbs in all racial groups. This predilection for ALM on plantar locations has led many to believe that trauma may be important in the etiology for ALM, since sun exposure has not been shown to be a risk factor for ALM.8,25
The majority of ALM are found on the lower limbs, even though the surface area of the palms and soles is similar. The sole of the foot is constantly exposed to pressure, friction, maceration, and irritation.8
In two retrospective ALM case series where a trauma history was taken, 13% of 119 patients25
and 25% of 35 patients7
reported prelesional trauma (ie—puncture wounds, stone bruises, friction blisters, contact dermatitis). Arguments against the trauma theory include the fact that the hand is exposed to more UV light and acute trauma.8
Furthermore, no change in incidence of melanoma of the soles was seen when African tribes became urbanized and began to wear shoes.7,26,27,28
Another factor that may play a role in the predilection of ALM for plantar locations is the fact that the density of melanocytes is 50% higher there than on the palm.8
Thickness and stage are important prognostic indicators for melanoma.12,17,18,21
Overall, about 70% of CMM were thin (0.01-1.00 mm) at diagnosis, and 68% were Stage I. In contrast, only 41% of ALM were classified as thin, and 38% were Stage I. ALM had significantly poorer melanoma-specific survival rates when compared to CMM overall. The distribution of thickness and stage at diagnosis between ALM and CMM may account for a large part of the survival differences. Interestingly, when controlled for thickness, ALM 10-year survival rates for tumors <1.00mm and those 2-4.00mm were still ~10-20% lower than for CMM overall. When controlled for stage, ALM 10-year survival rates for tumors at Stages II and III were 10-15% lower than for CMM overall. The lower survival rates seen in ALM may be secondary to reported different biological characteristics of the melanoma subtypes. It has been suggested that there are different genetic pathways in the development of melanoma.29
ALM have been reported to have significantly lower frequencies of BRAF mutations, which are often found in melanomas from intermittent sun exposure (ie—SSM or NM).30, 31
Furthermore, one study suggested that ALM are unique, in that they have constitutive activation of the phosphatidyl inositol 3 kinase signaling pathway.32
Another suggested that ALM are characterized by focused gene amplifications occurring early in tumorigenesis, and malignant cells are present beyond the histologically detectable boundary, thereby revealing one mechanism of local recurrence.33
Although these differences specific to ALM have been reported, they may not necessarily translate into survival differences; hence, the exact cause remains unknown.
Gender differences were also present in the distribution of ALM thickness and stage. Females had significantly higher percentages of Stage I and thin melanomas, while males had higher percentages of Stage III and thick melanomas. The distribution of tumor stage and thickness may also explain survival differences in males and females, since females had statistically significantly higher survival rates than males. When we adjusted for thickness or stage, there were no statistical differences in survival rates between males and females. Similarly, male patients with CMM overall have also been shown to have poorer survival rates relative to female patients in other studies, with increased tumor thickness at diagnosis being implicated as a causal factor.34,35
Non-Hispanic Whites had the highest percentage of thin and Stage I ALM, whereas Asian/Pacific Islanders had the highest percentage of Stage III and thick (>4.00 mm) ALM. Hispanic Whites also had high percentages of Stage III tumors. This distribution of ALM tumors may partly explain survival discrepancies among the different racial groups, since Asian/Pacific Islanders and Hispanic Whites also had the lowest survival rates. These results are consistent with previous results by Cormier et al who showed that minority populations had lower melanoma survival rates secondary to advanced stage presentation.12
When controlled for thickness or stage, there were no statistical difference between 5- and 10-year melanoma-specific survival rates in the different racial groups. These results are similar to previous studies that showed, after controlling for stage, similar survival rates among different racial groups with ALM.12,23,36,37
Our study had several limitations. Approximately 50% of the melanoma cases in the SEER database were classified histologically as “not otherwise specified,” and therefore excluded from the analyses. Reporting of melanomas as “NOS” has been a common problem and data limitation in SEER-based analyses.38
Exclusion of the “NOS” melanomas, however, had no statistically significant effects on the results. Furthermore, 74 tumors coded as ALM were reported to be located in anatomic sites other than the upper limbs and lower limbs. These tumors were excluded from the analyses, given their inconsistency with the definition of ALM. In addition, data was extremely limited for AJCC staging for ALM, with only ~60% of cases available for stage analyses. Finally, we used SEER data for this study. We had no information on socioeconomic status and access to health care, and therefore we were unable to examine these issues in the current study. These factors have been shown to be important for evaluating disparities in cancer survival and health care overall for minorities.12,13