Does in situ melanoma really come before invasive melanoma? Descriptive epidemiology questions this relationship.

While the incidence rates for skin melanoma have increased worldwide in the last decades, Breslow tumor thickness has decreased1. The incidence of in situ melanoma has also increased, and it doubled in the USA between 1988 and 20062. These recent trends are in part due to the diffusion of early diagnosis1,2, which is based on the assumption that the detection of less invasive lesions (i.e., those susceptible to more effective treatment) will prevent the occurrence of the more invasive and deadly ones. If the pattern for melanoma indicated a worsening progression from in situ to invasive lesions-thin, first, then thick-the mean age at diagnosis for such lesions should increase accordingly. We retrieved melanoma cases incident between 2000 and 2005 from theTuscany Cancer Registry archive. This is a population-based cancer registry active in central Italy since 1985 on a population of about 1.2 million inhabitants. Between 2000 and 2005, 1513 skin melanomas were newly diagnosed, 318 (21.0%) in situ and 1195 (79.0%) invasive. Among the latter, 607 (50.8%) were ≤1 mm, 410 (34.3%) >1 mm, while the Breslow thickness of 178 lesions (14.9%) could not be assessed. Themean ages of patients at diagnosis of melanomas in situ (57.69 years) and invasive melanomas (57.52) were similar (Student’s t-test, P = 0.87). However, among invasive melanomas, thin lesions (≤1 mm) were diagnosed at a younger age (54.03 years) than among in situ melanomas (P = 0.0014). By contrast, patients with >1 mm thick melanomas were older at the time of diagnosis (61.95 years) than patients with in situ melanomas (Table 1). These results are mainly due to lentigo malignant melanomas, which occur at a rather old age (mean age at diagnosis 71.3 years) and are more frequent among in situ (69/318, 21.6%) than among invasive melanomas (36/1195; 3.0%). According to the present data, in situmelanoma does not seem an obligate precursor of thin invasive melanoma, as it is diagnosed at an older age than invasive melanoma ≤1 mm. Although most of the results are driven by lentigo maligna melanomas, descriptive epidemiology suggests different pathways for in situ and invasive melanomas, at least for thin ones. There may be 2 different in situmelanomas, some with an indolent behavior and others which are more aggressive; micromelanomas invasive at diagnosis3may belong to the latter group.