Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi

ContextThe incidence of cutaneous melanoma has increased over the past several
decades, making its early diagnosis a continuing public health priority. The
ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) acronym
for the appraisal of cutaneous pigmented lesions was devised in 1985 and has
been widely adopted but requires reexamination in light of recent data regarding
the existence of small-diameter (≤6 mm) melanomas.Evidence AcquisitionCochrane Library and PubMed searches for the period 1980-2004 were conducted
using search terms ABCD and melanoma and small-diameter melanoma. Bibliographies of retrieved articles were
also used to identify additional relevant information.Evidence SynthesisAvailable data do not support the utility of lowering the diameter criterion
of ABCD from the current greater than 6 mm guideline. However, the data support
expansion to ABCDE to emphasize the significance of evolving pigmented lesions
in the natural history of melanoma. Physicians and patients with nevi should
be attentive to changes (evolving) of size, shape, symptoms (itching, tenderness),
surface (especially bleeding), and shades of color.ConclusionsThe ABCD criteria for the gross inspection of pigmented skin lesions
and early diagnosis of cutaneous melanoma should be expanded to ABCDE (to
include “evolving”). No change to the existing diameter criterion
is required at this time.

https://jamanetwork.com/journals/jama/articlepdf/199929/jcr40044.pdf

Early Diagnosis of Cutaneous Melanoma: Revisiting the ABCD Criteria

People with pale skin, red hair, freckles and an inability to tan--the 'red hair/fair skin' phenotype--are at highest risk of developing melanoma, compared to all other pigmentation types. Genetically, this phenotype is frequently the product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene. MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls pigment production. Minimal receptor activity, as in red hair/fair skin polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing MC1R activity stimulates the production of black/brown eumelanin. Pheomelanin has weak shielding capacity against ultraviolet radiation relative to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species. Several observations, however, complicate the assumption that melanoma risk is completely ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and ultraviolet radiation signature mutations are infrequently oncogenic drivers. Although linkage of melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet-radiation-independent events are likely to have a significant role. Here we introduce a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAF(V600E), into mice carrying an inactivating mutation in the Mc1r gene (these mice have a phenotype analogous to red hair/fair skin humans). We observed a high incidence of invasive melanomas without providing additional gene aberrations or ultraviolet radiation exposure. To investigate the mechanism of ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1r(e/e) background. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1r(e/e) mouse skin was found to have significantly greater oxidative DNA and lipid damage than albino-Mc1r(e/e) mouse skin. These data suggest that the pheomelanin pigment pathway produces ultraviolet-radiation-independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage. Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention.

/pdf/an-ultraviolet-radiation-independent-pathway-to-melanoma-19rpk4xfs1.pdf

An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background

These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.

U.K. guidelines for the management of cutaneous melanoma.

These guidelines reflect the best published data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to the guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2133.2010.09883.x

Revised U.K. guidelines for the management of cutaneous melanoma 2010.

Cutaneous melanoma is rapidly becoming a potentially curable cancer if it is detected and properly treated in an early phase of development. Unlike other cancers, which are usually hidden from detection until they are relatively large or metastatic disease has occurred, cutaneous melanoma is readily detectable simply by examining the skin. Information is now available that will be useful in selecting individuals at greatest risk. The most important melanoma risk factors (in decreasing order of importance) for a given individual are as follows: a persistently changed or changing mole, adulthood, irregular varieties of pigmented lesions (including dysplastic moles and lentigo maligna), a congenital mole, Caucasian race, a previous cutaneous melanoma, a family history of cutaneous melanoma, immunosuppression, sun sensitivity, and excessive sun exposure. Selective screening and appropriate treatment of individuals who have these risk factors may reduce the morbidity and mortality of cutaneous melanoma.

Risk factors for cutaneous melanoma: A practical method of recognizing predisposed individuals

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Risk factors for cutaneous melanoma: A practical method of recognizing predisposed individuals