Sun exposure and host phenotype as predictors of cutaneous melanoma associated with neval remnants or dermal elastosis

Abstract

Recent research suggests that cutaneous melanomas may arise through 2 distinct pathways, characterized by chronic sun exposure on one hand and nevus-prone phenotype of the host on the other. Two histological characteristics of melanoma consistent with these divergent origins are dermal elastosis in adjacent skin and neval remnants contiguous with the tumor, respectively. To further explore causal heterogeneity in melanoma, we compared sun exposure histories and phenotypic characteristics among a population-based sample of patients newly diagnosed with cutaneous melanoma with and without contiguous neval remnants or dermal elastosis. Tissue blocks were obtained for 141 patients: 53 with superficial spreading melanoma (SSM) of the back, 42 with SSM of head and neck (H & N), and 39 and 7 with lentigo maligna/lentigo maligna melanoma (LM/LMM) of the H & N and back, respectively. Melanomas of the H & N were less likely than those on back to have neval remnants (adjusted OR 0.6, 95% CI 0.3-1.4), but were significantly more likely to have dermal elastosis (adjusted OR 9.3, 95% CI 3.5-25). In site-specific analyses, we found that H & N melanomas with neval remnants were more likely than those without neval remnants to arise in people with more than 60 nevi (adjusted OR 2.1, 95% CI 0.3-14.3), but were less likely to arise in those with more than 20 actinic keratoses. Less marked associations were observed for melanomas of the back. High levels of sun exposure strongly predicted dermal elastosis for H & N melanomas (OR 22.5, 95% CI 2.1-245), but not for melanomas of the back (OR 2.1, 95% CI 0.4-11). We conclude that melanomas with different histologic characteristics have different risk factor profiles, particularly on the head and neck. These data accord with the hypothesis that melanomas arise through different causal pathways. ' 2006 Wiley-Liss, Inc.

Changing biology of cutaneous melanoma

“…The first one is induced by an increased intermittent sun exposure and is associated with a younger age at the time of diagnosis, multiple nevi and CM of the trunk and lower limbs. According to that theory, in our population a higher percentage of CM would be expected to develop on the trunk over the time [2,19]. As in other European countries, tumors were indeed predominantly located on the trunk or lower limb, but there were no statistical changes in the frequency of tumors on the trunk between the periods [5,18].…”

“…The second developmental pathway is associated with chronic sun exposure and markers of skin damage (dermal elastosis). CM is located predominantly on the head and neck and occurs later in life [2,19]. On the basis of the increased age of patients at the time of diagnosis (53.32 years in the last observed period vs. 36.58 in the first), it is possible that the increased amount of intermittent sun exposure has led to the changes in tumor development that are usually associated with chronic patterns of exposure [2,3].…”

Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006

“…30,31 Patients with cutaneous head and neck melanoma were older than those with melanoma on other skin sites, whereas patients with melanoma on the trunk were younger at diagnosis. 32 A meta-analysis, based on information from 29 published articles and 24 independent study groups, found that associations of intermittent sun exposure, continuous sun exposure, and sunburns were each higher for usually sunexposed anatomic sites than for occasionally sunexposed sites.…”

Testing the divergent pathway hypothesis for melanoma: recent findings and future challenges

“…The concordant findings from descriptive and analytical studies are consistent with melanomas at different body sites arising through different pathways, but do not shed light on the mechanisms of pathogenesis. To address this issue, investigators have systematically appraised histological features and noted that melanomas arising from a benign melanocytic nevus differ from those arising de novo, being more frequent on the trunk than the head and neck, and being associated with young age and high nevus counts [20][21][22][23]. These congruent findings point to one group of melanomas arising through a high-nevus/low-sunlight pathway (predominantly on the trunk) and another group of mainly head and neck melanomas arising through a low-nevus/high-sunlight pathway.…”