Body site of cutaneous malignant melanoma : primary tumor location in relation to phenotypic and prognostic factors

Abstract

The main purpose of this thesis was to analyze the primary body site of cutaneous malignant melanoma (CMM) in relation to phenotypic traits and prognosis. It is clear that several characteristics of CMM are different, and vary with the skin location where the tumor originated. The different types of sun exposure (chronic/occupational and/or intermittent/recreational) on different parts of the skin could be one of the reasons for this. A new computer program, EssDoll©, developed for detailed studies of site of CMM was used in this thesis.

A cohort of 756 patients, with head-neck CMM was analyzed. The CMM density was 3.4 times higher in the face compared to skin surfaces outside the head-neck area. Similarly, nodular melanoma (NM) was 2.3- and lentigo maligna melanoma (LMM) 74 times more dense in the face. It is known that chronic exposure to UV-fadiation is a risk factor for LMM, and our findings suggest such a relationship for NM as well. 'Me mean age at diagnosis was 12 years higher for CMM in the head-neck compared to sites outside the head-neck (66 vs. 54 yr.). Ibis relatively later diagnose supports the view of a natural tan to be somewhat protective for CMM. We found tumor thickness to be the only statistically significant prognostic factor for patients with head-neck CMM. The surgical resection margin at operation of the primary tumor (1-10 vs. 2: 11 mm) had no impact on patient outcome.

A software, EssDoll©, was developed and used in a cohort of 2517 patients with 2608 primary CMMs. The primary sites of CMMs was plotted on a movable doll and linked to patient ID. With this software one or more skin area(s) can be chosen for analysis. Using this type of analysis we confirmed that the predominant site for CMM in men was the trunk, and in women the lower extremities. Superficial spreading melanoma (SSM) and NM were most common on the trunk while LMM was most common in the head-neck.

Patients with hereditary CMM (HCMM) and patients who have been treated for a sporadic CMM have an increased risk to develop new CMM. The anatomic sites of CMM in these patient groups were analyzed separately. in the database there were 104 patients with HCMM and 69 patients with more than one sporadic CMM (MCMM). For patients with sporadic MCMM, the second tumor often arose in the same body field as the first. The concordance was statistically significant (p<0.0001). This might imply that the skin surrounding a CMM has undergone predisposing changes for yet another CMM ("field effect"). Furthermore, the patients with HCMM had significantly less CMM on the head-neck and more on the trunk compared to patients with one sporadic CMM (p=0.05). The reason for this could be an increased sensitivity to intermittent sun exposure in HCMM patients.

The site-specific prognosis was analyzed in a cohort of 1,891 patients. The body surface was divided into 48 separate areas (which, for reasons of statistical power, were combined into 24 areas) with no consideration taken to outcome. The multivariate analyzes, adjusted for previously established prognostic factors for patents with localized disease, showed a significantly elevated risk for CMM death in patients with primary CMM site in the middle and lower back (odds ratio 2.0, p=0.03) compared to those with tumors in the reference area. In another model, where all areas were analyzed in pairs also the middle and lower back and, in addition, the dorsal shoulders, clavicular areas superior back, supra mammary and mammary areas were associated with an adverse prognosis. Tumors on the arms, calves, achilles, knee and poplitea. area were associated with a more favorable prognosis.

In conclusion, a number of different characteristics of CMM have been connected to the primary anatomical site.