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Practice

Melanoma

Robert Micieli and Kucy Pon
CMAJ May 13, 2019 191 (19) E535; DOI: https://doi.org/10.1503/cmaj.181500
Robert Micieli
Faculty of Medicine (Micieli, Pon), University of Toronto; Division of Dermatology, Sunnybrook Health Sciences Centre (Pon), Toronto, Ont.
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Kucy Pon
Faculty of Medicine (Micieli, Pon), University of Toronto; Division of Dermatology, Sunnybrook Health Sciences Centre (Pon), Toronto, Ont.
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Sun exposure plays an important role in melanoma pathogenesis

More than 90% of melanomas in the 3 most common genetic subtypes (BRAF, RAS, NF1) have a substantial ultraviolet signature.1 Clinically, melanomas most commonly appear on sites of chronic (i.e., face, neck) or intermittent sun exposure (i.e., trunk, legs) as superficial spreading (Figure 1), nodular or lentigo maligna melanoma (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.181500/-/DC1).

Figure 1:
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Figure 1:

ABCDE criteria (Asymmetric shape, irregular Border, Colour variation, Diameter > 6 mm [about the size of a pencil eraser] and Evolution [noted on history and when compared with previous size]) of a typical superficial spreading melanoma, characterized as a plaque with flat and raised areas. Image obtained from the National Cancer Institute.

Melanomas also occur on sites of minimal sun exposure

Genome sequencing of acral (on palms and soles) and mucosal melanomas has shown that although sun exposure may play a role, it is not the primary mutational driver.2 These melanomas may share a pathogenesis similar to that of other noncutaneous malignancies.

The mitogen-activated protein kinase pathway is implicated in almost all melanomas

This pathway stimulates cell growth and survival. BRAF, RAS and NF1 mutations are part of this pathway and represent 50%, 25% and 15% of all melanomas, respectively.1 Genome-wide studies have helped identify important immunohistochemistry markers for diagnosis (e.g., anti–programmed cell death 1 [anti–PD-1], anti–cytotoxic T-lymphocyte-associated protein 4 [anti–CTLA4])3 as well as adjuvant immunotherapies and targeted therapies (i.e., BRAF or MEK inhibitors) to improve survival of patients with advanced melanoma.4

Of all melanomas, 10% are amelanotic or hypopigmented and may be diagnostically challenging5

They are most common in patients with Fitzpatrick type I skin and chronic sun damage (actinic keratoses), and are located on sun-exposed sites (e.g., face, neck, upper arms, hands).5 The differential diagnosis for evolving red or pink macules, plaques or nodules should include amelanotic melanoma, especially in the aforementioned patients and locations. KIT, a tyrosine kinase inhibitor, is frequently mutated in amelanotic melanoma.

Any lesions suspicious for melanoma should be referred to dermatology

A pigmented lesion with any of the ABCDE criteria (Figure 1) should raise suspicion for melanoma. Wide, local excision with appropriate margins is the definitive treatment. In cosmetically sensitive areas (e.g., face), Moh surgery, in which thin layers of the tumour are sequentially removed until only cancer-free tissue remains, may be preferred.

Footnotes

  • Competing interests: None declared.

  • This article has been peer reviewed.

References

  1. ↵
    Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell 2015;161:1681–96.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Hayward NK,
    2. Wilmott JS,
    3. Waddell N,
    4. et al
    . Whole-genome landscapes of major melanoma subtypes. Nature 2017; 545:175–80.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Massi D,
    2. Simi L,
    3. Sensi E,
    4. et al
    . Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma. Mod Pathol 2015;28:487–97.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Long GV,
    2. Hauschild A,
    3. Santinami M,
    4. et al
    . Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 2017;377:1813–23.
    OpenUrlPubMed
  5. ↵
    1. Wee E,
    2. Wolfe R,
    3. Mclean C,
    4. et al
    . Clinically amelanotic or hypomelanotic melanoma: anatomic distribution, risk factors, and survival. J Am Acad Dermatol 2018;79:645–51.e4.
    OpenUrl
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Canadian Medical Association Journal: 191 (19)
CMAJ
Vol. 191, Issue 19
13 May 2019
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Melanoma
Robert Micieli, Kucy Pon
CMAJ May 2019, 191 (19) E535; DOI: 10.1503/cmaj.181500

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Robert Micieli, Kucy Pon
CMAJ May 2019, 191 (19) E535; DOI: 10.1503/cmaj.181500
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    • Sun exposure plays an important role in melanoma pathogenesis
    • Melanomas also occur on sites of minimal sun exposure
    • The mitogen-activated protein kinase pathway is implicated in almost all melanomas
    • Of all melanomas, 10% are amelanotic or hypopigmented and may be diagnostically challenging5
    • Any lesions suspicious for melanoma should be referred to dermatology
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