Melanoma

Last reviewed: 6 May 2023

Last updated: 20 Jan 2023

Incidence of melanoma is increasing, with a lifetime risk in the US of 1 in 27 in men and 1 in 40 in women.

Melanoma is the third most common skin cancer, but is the most common cause of skin cancer-related death.

Approximately 17% of patients develop metastatic disease.

Reducing exposure to ultraviolet light is critical for primary prevention of melanoma.

Clinical features of lesion asymmetry, border irregularity, color variability, diameter >6 mm, and evolution over time should raise suspicion for melanoma and prompt further assessment with dermoscopy.

The prognosis depends on the stage at diagnosis. Over 99% of patients with in-situ melanoma will be cured with simple excision.

Targeted therapies such as immune checkpoint inhibitors and BRAF inhibitors have revolutionized the treatment of metastatic melanoma. Five-year survival rates have improved since the approval of these therapies and are now approaching 30%.

Definition

Melanoma is a malignant tumor arising from melanocytes. It is among the most common forms of cancer in young adults and typically presents as a new or changing pigmented (brown or black) skin lesion.[1] The incidence of melanoma peaks in adults more than 70 years of age.[1]

Lesions are often on sun-exposed anatomic locations in people with Fitzpatrick type I (white) skin.

Diagnosis is by physical examination and confirmed by histopathological analysis of a biopsy.[2]

Early stage melanoma has an overall survival rate of nearly 100%, while metastatic melanoma can be rapidly fatal.[1]

Noncutaneous melanomas may arise from melanocytes in the uvea, meninges, or mucosal membranes.[2] Their management is beyond the scope of this topic.

History and exam

Key diagnostic factors

altered pigmented lesion (ABCDE signs)
melanocytic lesion that does not resemble surrounding melanocytic nevi ("ugly duckling")
spontaneous bleeding or ulceration of a pigmented lesion
constitutional symptoms
nail sign: persistent single-nail melanonychia striata
nail sign: Hutchinson sign
atypical dermoscopy findings
fixed lymphadenopathy
in-transit metastases

More key diagnostic factors

Risk factors

family history of melanoma
personal history of melanoma
personal history of skin cancer (including actinic damage)
history of atypical nevi
Fitzpatrick skin type I or II (white skin)
red or blond hair color
high freckle density
sun exposure
sun bed use
light eye color
increased numbers of benign-appearing melanocytic nevi
large congenital nevi
immunosuppression
xeroderma pigmentosum

More risk factors

Diagnostic investigations

1st investigations to order

dermoscopy
skin biopsy
immunohistochemistry

More 1st investigations to order

Investigations to consider

sentinel lymph node biopsy
chest/abdominal/pelvic CT scan
whole-body PET scan
brain imaging (CT or MRI)
BRAF mutational analysis
NRAS mutational analysis
serum lactate dehydrogenase (LDH)

More investigations to consider

Emerging tests

CDKN2A mutational analysis

Treatment algorithm

ACUTE

early stage melanoma (melanoma in situ, stage I, stage II)

resectable advanced melanoma (stage III and stage IV)

unresectable advanced disease (stage III and stage IV)

Contributors

Authors

Prachi Bhave, BE (Hons), MBBS, FRACP

Medical Oncologist

Peter MacCallum Cancer Centre

Victoria

Australia

Disclosures

PB has received honoraria from Novartis and sponsorship from MSD and Novartis.

Yin Wu, MRCP, PhD

Wellcome Trust Clinical Research Career Development Fellow and Honorary Consultant Medical Oncologist

Peter Gorer Department of Immunobiology

King's College London

Department of Medical Oncology

Guy's and St Thomas' NHS Foundation Trust

London

Disclosures

YW is funded by the Wellcome Trust.

Pablo Fernandez-Peñas, MD, PhD, FACD

Associate Professor of Dermatology

The University of Sydney

Sydney

Australia

Disclosures

PF-P declares that he has no competing interests with the topic Melanoma. PF-P has advisory roles with Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Leo, Novartis, Lilly, Abbvie, Janssen, Celgene (psoriasis, atopic eczema, hidradenitis), Roche, Merck Sharp & Dohme, Sun Pharmaceuticals, Novartis, and Sanofi. He has been paid to do research for Incyte Europe Sarl, and clinical trials for Arena, Akaal Pharma, Xoma, Kyowa Hakko Kirin, AbbVie, OncoSec, Lilly, CSL Behring, Boehringer Ingelheim, Pfizer, mRage, Eisai, Jiansu Hengrui, Bristol-Myers Squibb, Sun Pharma, Novartis, Roche, Galderma, Regeneron, UCB, GlaxoSmithKline, and Amgen.

Acknowledgements

Dr Prachi Bhave, Dr Yin Wu, and Dr Pablo Fernandez-Peñas would like to gratefully acknowledge Dr Robyn P.M. Saw, Dr Sophie E. Papa, Dr Alexander M. Menzies, Dr Philip Friedlander, Dr Hobart W. Walling, and Dr Brian L. Swick, previous contributors to this topic.

Disclosures

RPMS is on the advisory board for Novartis, MSD, and Qbiotics and has previously been on the advisory board for Amgen; he has received honoraria from BMS and Novartis. SEP has received honoraria from BMS, MSD, and Novartis to attend conferences; she has participated in advisory boards for BMS, MSD, Amgen, Roche, and GSK. AMM has received honoraria from Novartis and BMS; he is on the advisory boards of MSD and Chugai. PF is a consultant for Genentech. HWW and BLS declare that they have no competing interests.

Peer reviewers

David Cassarino, MD, PhD

Assistant Professor

Department of Pathology and Laboratory Medicine

University of California

Los Angeles

Disclosures

DC declares that he has no competing interests.

James DeBloom, MD

Dermatologist/Dermatologic Surgeon

President of the South Carolina Skin Cancer Center

Greenville

Disclosures

JB declares that he has no competing interests.

Mai Brooks, MD, FACS

Associate Director

JCCC Women's Cancers Program Area

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles

Disclosures

MB declares that she has no competing interests.

Karol Sikora, MA, MBBCh, PhD, FRCR, FRCP, FFPM

Medical Director

CancerPartnersUK

London

Disclosures

KS declares that he has no competing interests.

Differentials
- Benign/dysplastic melanocytic nevi
- Seborrheic keratosis
- Pigmented basal cell carcinoma
More Differentials
Guidelines
- Systemic therapy for melanoma
- Treatment for brain metastases
More Guidelines
Patient leaflets
Skin cancer (melanoma): what is it?
Skin cancer (melanoma): how is it diagnosed and treated?
More Patient leaflets
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Melanoma

Summary

Definition

History and exam

Key diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Emerging tests

Treatment algorithm

early stage melanoma (melanoma in situ, stage I, stage II)

resectable advanced melanoma (stage III and stage IV)

unresectable advanced disease (stage III and stage IV)

Contributors

Authors

Prachi Bhave, BE (Hons), MBBS, FRACP

Disclosures

Yin Wu, MRCP, PhD

Disclosures

Pablo Fernandez-Peñas, MD, PhD, FACD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

David Cassarino, MD, PhD

Disclosures

James DeBloom, MD

Disclosures

Mai Brooks, MD, FACS

Disclosures

Karol Sikora, MA, MBBCh, PhD, FRCR, FRCP, FFPM

Disclosures

Differentials

Guidelines

Patient leaflets

Log in or subscribe to access all of BMJ Best Practice

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