melanoma is the sixth most common malignancy in the united states ; there were an estimated 68,120 new cases of invasive melanoma in 2010 with 8,700 deaths due to the disease 1 , 2 . when compared to younger age groups ,
mortality is significantly higher in the elderly implicating age as a poor prognostic factor 3 . as the proportion of the elderly among the world population continues to grow3 ,
nearing 20% in developed countries4 , so will the importance of melanoma characterization and proper risk stratification in that age group .
the clinical presentation and pathological characteristics in melanoma of the elderly differ from that of their younger counterparts .
melanoma of the elderly has been shown to be more common in men and to be discovered later in its development .
the incidence of ulceration , high mitotic index , and advanced breslow thickness have been shown to be higher in older age groups5 - 8 .
paradoxically , despite lower overall survival in elderly with malignant melanoma , the rate of positive sentinel lymph nodes ( sln ) decreases with age3 , 9 - 11 .
this observation remains unexplained but is likely related at least in part to atrophy of skin lymphatics that occur with age12 .
given the differing clinical presentation , pathological characteristics , and heightened mortality rates of elderly melanoma patients , we aimed to compare disease characteristics and clinical outcomes of patients 70 years of age and older versus under 70 years old .
we reviewed 610 patients with malignant melanoma requiring sln biopsy entered into a prospective sln database from mayo clinic arizona , treated from june 1997 to june 2010 .
disease characteristics and clinical outcomes were compared between patients 70 yrs vs. < 70 yrs of age .
subset analysis was performed with a breakdown between age groups of < 50 , 50 - 59 , 60 - 69 and > 70 , but the statistical power of this analysis was limited due to the smaller number of events in the groups .
primary melanoma anatomic locations were divided in four locations : head and neck , lower extremity , trunk , and upper extremity .
characteristics of the primary melanoma that were analyzed included : breslow 's depth , t - stage ( < 1 mm , 1 - 2 mm , 2.01 - 4 mm , > 4 mm ) , ulceration , tumor infiltrating lymphocytes ( til ) , preexisting nevus , angiolymphatic invasion , perineural invasion , and mitotic rate .
disease outcome measures included type of recurrence ( local / in - transit , regional , systemic ) , time to recurrence , time to local / in - transit recurrence , disease - specific mortality , and overall mortality .
continuous variables were compared between groups using two - sample independent samples t - tests .
disease outcomes were plotted using kaplan - meier curves and compared between groups using cox proportional hazards models .
the mean age in the < 70 years old group was 52.2 ( 14 - 69 ) . among the elderly group ( 70 yrs ) ,
the mean age was 77.3 ( 70 - 97 ) , there was a greater predominance of men , 153 ( 65% ) compare to those < 70 yrs , where men comprised 56% ( p=0.04 ) , table 1 .
the location of melanomas was significantly different between the elderly and younger patients ( p<0.001 ) .
the elderly patients had a higher proportion of head and neck melanomas ( 34% ) relative to the younger patients ( 19% ) , whose most prevalent site was the trunk ( 35% ) .
elderly patients had thicker tumors , with 43% of elderly patients had a t3 or t4 melanoma compared to 23% in the non - elderly ( p<0.001 ) .
patients with age 70 had a greater mean number of mitotic figures , 3.6/mm vs. 2.7/mm ( p=0.005 ) including a greater preponderance of lesions with a high mitotic rate > 5/mm ( 29% vs 17% , p=0.003 .
tumors in the elderly were less likely to arise from a pre - existing nevus , 17% vs. 36% ( p=0.003 ) .
overall , the prevalence of sln metastases was similar between elderly and non - elderly patients .
when the incidence of sln metastases was stratified by t stage ( t1/t2 and t3/t4 ) , the rate of positive slns was dramatically less common in elderly patients with t3 or t4 melanoma versus their younger counterparts ( 18% vs. 33% , p=0.02 ) .
the median follow up time was 3.8 years ( range 0 - 12.6 years ) .
the elderly patients had a higher rate of recurrence ( including local / in - transit , regional , or systemic recurrence ) relative to the younger patients ( 25.2% vs 9.1% 5 years after surgery ; hazard ratio [ hr]=2.6 , p<0.001 ; figure 1a ) .
additionally , the elderly patients had a higher rate of local / in - transit recurrence ( 14.5% vs 3.4% 5 years after surgery ; hr=3.6 , p<0.001 ; figure 1b ) and systemic recurrence ( 14.9% vs 6% 5 years after surgery ; hr=1.83 , p=0.05 ; figure 1c ) .
subset analysis of age groups < 50 , 50 - 59 , 60 - 69 and > 70 showed progressively worse outcomes with age , as expected .
recurrence - free survival rates in the subset analysis were 91.8% , 85.6% , 82% , and 60% respectively for age groups in ascending order .
relative to age group < 50 , hazard ratios for the age groups 50 - 59 , 60 - 69 , and > 70 were 1.98 ( p=0.08 ) , 2.15 ( p=0.03 ) , and 5.42 ( p<0.001 ) respectively .
5-year mortality rate from all causes was greater in the elderly group , 29.8% vs. 12.3% 5 years after surgery ( hr=3.0 , p<0.001 ; figure 2a ) . additionally , 5-year disease - specific mortality was higher for those 70 years old : 16.1% vs. 8.2% ( hr=2.3 , p=0.004 ; figure 2b ) . in a multivariate model of melanoma - specific survival
, age remained significant after adjusting for known prognostic factors of tumor thickness and positive sln status .
in our cohort of patients undergoing sln biopsy , melanoma in the elderly was more common on the head and neck , less likely to arise from a pre - existing nevus , had greater mean tumor thickness and more mitotic figures than melanoma in their younger counterparts .
additionally , higher t - stage melanoma in the elderly was less likely to result in positive sentinel node biopsy .
they were more likely to have recurrence , including a higher rate of local / in - transit recurrence and systemic recurrence .
studied 399 patients with melanoma who underwent sln biopsy and compared patients 50 years vs. > 50 years .
they found the melanoma patients > 50 to have thicker lesions and a higher incidence of ulceration but no difference in the incidence of lymph node metastases .
overall survival was worse among the group > 50 and age was a significant prognostic variable in multivariate analysis13 .
data from the seer database and medicare enrollment and claims files , showed that increasing age after 65 years and melanoma detection by a dermatologist were significantly predictive of survival on multivariate analysis in a population of over 2000 patients 14 . in a large dataset of 17,600 melanoma patients , age was an independent prognostic factor for overall survival which was consistent within each thickness subgroup9 .
worse prognosis in the elderly may be attributable to the fact that the elderly , especially elderly men , melanoma has been shown to have a more rapid growth rate15 , thicker tumors16 and histologic ulceration16 .
age as a poor prognostic factor may be the result of weakened immune defense mechanisms 17 , 18 , which may play a role in melanoma progression .
lastly , competing co - morbidities are much more prevalent in older patients , further contributing to higher overall mortality .
elderly melanoma patients have been shown to present with tumors of advanced breslow level 3 , 9 , 19 , 20 .
late diagnosis has been implicated as a cause for thicker melanoma with poor prognosis in the elderly .
some reasons may include scarcely visible anatomical locations of new pigmented lesions ( i.e. scalp , back ) , loss of a partner 's input on home examination , poor vision , less importance placed on changing lesions , and confusing new or changing benign seborrheic keratoses for pigmented lesions21 , 22 .
studies have shown disproportionately low screening of elderly men despite this population accounting for 44% of melanoma cases discovered23 .
higher incidence of head and neck melanoma is likely attributable to cumulative photodamage and higher incidence of lentigo maligna melanoma as patients age .
showed that lentigo maligna melanoma was the only melanoma subtype with increasing incidence over a ten - year period and was more common in men 65 years 24 .
as the percentage of elderly persons in the world 's population continues to grow , physicians performing melanoma screening should devote heightened attention to heavily sun - exposed sites where melanoma is more and more commonly discovered . our data confirmed previously reported findings that the elderly are less likely to have melanoma associated with a pre - existing nevus25 .
malignant progression may be the result of continuous and cumulative photodamage to melanocytes not within a nevus26 .
this has clinical implications to patient education and early detection of melanoma in that age group . when counseling elderly patients regarding self - screening , a shift of focus from characteristics of changing nevi ( abcde of melanoma ) to awareness of any new growths may lead to more routine screening and earlier detection .
our data demonstrated that the mitotic rate in the elderly melanoma patients was higher than their younger counterparts .
mitotic rate has been associated with worse clinical outcomes in melanoma patients and has been identified as an independent prognostic factor in multiple studies 27 - 29 . in a multifactorial analysis of 10,233 patients with clinically localized melanoma ,
mitotic rate was the second best prognostic factor of survival behind tumor thickness 29 . in a series of more than 1200 cases ,
higher mitotic rate tumor burden has also been implicated as a factor contributing to a greater likelihood of local / in - transit recurrence and poor clinical outcomes 30 .
. showed mitotic rate is associated with positive sln , but the impact of mitotic activity on sln result was less in the elderly compared to younger cohorts 31 .
our data was consistent with these observations as our elderly population had more mitotic figures , greater number of non - regional recurrences , and worse clinical outcomes .
additionally , they had a lower positive sln rate , indicating that mitotic activity had less impact on sln result in the elderly compared to younger patients . in advanced t - stage melanoma , despite worse disease - specific and overall mortality , the elderly had far fewer cases of positive sln biopsies .
studied 5 age groups of melanoma patients in a large series of over 3000 patients .
they showed a progressive decline in incidence of sln metastasis with increasing age across all five age groups .
the oldest group ( > 60 years ) had a positive sln rate of 14.4% , significantly less than the next nearest age groups 3 .
our cohort of elderly patients ( 70 years ) demonstrated a comparable rate of positive sln in 11% .
the reason for fewer cases of positive sentinel lymph node biopsies remains uncertain but may be accounted by altered lymphatic drainage in the elderly12 .
although the mode of spread in any cancer is never certain , it appears that like younger patients , melanoma in the elderly principally spreads along lymphatic routes as there are more in - transit metastases noted in this age group 32 .
uv irradiation has been shown to induce vegf - a - mediated damage of cutaneous lymphatic channels 33 , 34 .
lifelong accumulation of photodamage is likely contributory to disruption of lymphatic channels , as well as gravity - dependent degeneration , disallowing complete migration of tumor cells to the sentinel node in areas of atrophied lymphatic channels in the elderly .
time to recurrence has been shown to be an independent predictor of post - recurrence survival35 .
additionally , advanced age at the time of recurrence diagnosis has been associated with poor prognosis 36 - 38 .
studied 279 melanoma patients with recurrence and found that those patients who had recurrence in 12 months or less from treatment of primary melanoma had significantly worse post - recurrence survival and progression - free survival rates35 .
a recent long - term follow - up study of 2487 patients showed that advanced age , male sex , high pn , and distant metastases as the first site of recurrence were associated with worse survival outcomes after the manifestation of recurrent disease38 .
subset analysis of age groups < 50 , 50 - 59 , 60 - 69 , > 70 was of limited statistical power because of small number of events in each group .
data was retrieved only from patients undergoing sentinel lymph node biopsy ; given the potential selection bias , it may not be valid to generalize conclusions to the entire elderly population with melanoma .
lastly , the follow - up period is limited to a mean of 3.8 years , which may influence outcome data to reflect more poorly on the elderly population .
given the differing clinical presentation , primary melanoma characteristics , and disparate disease - specific outcomes of melanoma in the elderly compared to non - elderly patients , clinicians and surgeons should be mindful of proper screening and risk - stratification of elderly patients when participating in their care . due to the higher risk of in - transit disease , follow - up should focus on loco - regional recurrences .
many adjuvant clinical trials are geared to patients with lymph node positive disease . due to the fact that the elderly have a much lower incidence of lymph node positive disease but otherwise poorer prognosis
, age may need to be included when developing clinical trials in order to evaluate the efficacy of adjuvant therapy in this patient population .
 purpose : age is a poor prognostic factor in melanoma patients . 
 elderly melanoma patients have a different presentation and clinical course than younger patients . 
 we evaluated the impact of age 70 years ( yrs ) on the diagnosis and natural history of melanoma.methods : retrospective review of 610 patients with malignant melanoma entered into a prospective sentinel lymph node ( sln ) database , treated from june 1997 to june 2010 . 
 disease characteristics and clinical outcomes were compared between patients 70 yrs vs. < 70 yrs of age.results : 237 patients ( 39% ) were 70 yrs . 
 elderly patients had a higher proportion of head and neck melanomas ( 34% vs. 20% , p<0.001 ) , and greater mean tumor thickness ( 2.4 mm vs. 1.8 mm , p<0.001 ) . 
 a greater proportion of t3 or t4 melanoma was seen in the elderly ( p<0.001 ) as well as a greater mean number of mitotic figures : 3.6/mm2 vs. 2.7/mm2 ( p=0.005 ) . despite greater mean thickness , the incidence of sln metastases was less in the 70 yrs group with t3/t4 melanomas ( 18% vs. 33% , p=0.02 ) . 
 the elderly had a higher rate of local and in - transit recurrences , 14.5% vs. 3.4% at 5 yrs ( p<0.001 ) . 
 5 yr disease - specific mortality and overall mortality were worse for those 70 yrs : 16% vs. 8% ( p=0.004 ) , and 30% vs. 12% ( p<0.001 ) , respectively.conclusions : elderly ( 70 yrs ) melanoma patients present with thicker melanomas and a higher mitotic rate but have fewer sln metastases . 
 melanoma in the elderly is more common on the head and neck . 
 higher incidence of local / in - transit metastases is seen among the elderly . 
 five - year disease - specific mortality and overall mortality are both worse for these patients . 