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Cutaneous melanoma
Background
Overview
Definition
Melanoma is a malignant tumor that arises from pigment-containing cells known as melanocytes, which occurs principally in the skin, but also more rarely in the mouth, intestines, or eyes.
1
Pathophysiology
Melanoma is caused by genetic mutations in melanocytes in response to UV-induced DNA damage.
2
Epidemiology
The incidence of melanoma in the US is estimated at 21.6 cases per 100,000 persons-year.
3
Disease course
The complex interaction between exogenous and endogenous triggers, tumor-intrinsic, and immune-related factors increase the proliferation of melanocytes that is accompanied by genetic mutations leading to malignant transformation of melanocytes to melanoma, which may further metastasize to lymph nodes, skin, lungs, and CNS.
4
Prognosis and risk of recurrence
The 5-year and 10-year relative survival for melanoma in the US is around 91.3% and 89.1%, respectively. The relative risk of recurrence for patients < 45 years and ≥ 45 years is 11.89 and 8.36, respectively.
5
Guidelines
Key sources
The following summarized guidelines for the evaluation and management of cutaneous melanoma are prepared by our editorial team based on guidelines from the Congress of Neurological Surgeons (CNS 2025), the European Society of Medical Oncology (ESMO 2025,2020), the American Academy of Family Physicians (AAFP 2024), the American Society of Clinical Oncology (ASCO 2023), the U.S. Preventive Services Task Force (USPSTF ...
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Screening and diagnosis
Classification and risk stratification
Staging: as per ESMO 2025 guidelines, use the AJCC TNM 8th edition system for melanoma staging.
B
TNM classification for cutaneous melanoma
Tumor classification
Tx: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Melanoma in situ
T1a: Tumor < 0.8 mm in thickness without ulceration
T1b: Tumor < 0.8 mm in thickness with ulceration; 0.8-1 mm with or without ulceration
T2a: Tumor 1.01-2 mm in thickness without ulceration
T2b: Tumor 1.01-2 mm in thickness with ulceration
T3a: Tumor 2.01-4 mm in thickness without ulceration
T3b: Tumor 2.01-4 mm in thickness with ulceration
T4a: Tumor > 4 mm in thickness without ulceration
T4b: Tumor > 4 mm in thickness with ulceration
Lymph node classification
Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis; no presence of in-transit, satellite, and/or microsatellite metastases
N1a: 1 clinically occult (detected by sentinel lymph node biopsy); no presence of in-transit, satellite, and/or microsatellite metastases
N1b: 1 clinically detected; no presence of in-transit, satellite, and/or microsatellite metastases
N1c: No regional lymph node metastasis; presence of in-transit, satellite, and/or microsatellite metastases
N2a: 2-3 clinically occult (detected by sentinel lymph node biopsy) tumor-involved nodes; no presence of in-transit, satellite, and/or microsatellite metastases
N2b: 2-3 tumor-involved nodes, ≥ 1 clinically detected; no presence of in-transit, satellite, and/or microsatellite metastases
N2c: 1 clinically occult or clinically detected tumor-involved nodes; presence of in-transit, satellite, and/or microsatellite metastases
N3a: ≥ 4 clinically occult (detected by sentinel lymph node biopsy) tumor-involved nodes; no presence of in-transit, satellite, and/or microsatellite metastases
N3b: ≥ 4 tumor-involved nodes, ≥ 1 clinically detected, or presence of any number of matted nodes; no presence of in-transit, satellite, and/or microsatellite metastases
N3c: ≥ 2 clinically occult or clinically detected tumor-involved nodes and/or presence of any number of matted nodes; presence of in-transit, satellite, and/or positive microsatellite metastases
Distant metastasis
M0: No distant metastasis
M1a: Distant metastasis to skin, soft tissue including muscle and/or nonregional lymph node
M1b: Distant metastasis to lung with or without M1a sites of disease
M1c: Distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease
M1d: Distant metastasis to CNS with or without M1a, M1b, or M1c sites of disease
Stage cannot be fully assessed
Diagnostic investigations
Physical examination
As per ESMO 2025 guidelines:
Obtain a dermatoscopy performed by an experienced physician to enhance diagnostic accuracy of melanoma.
B
Perform a whole-body physical examination with special attention to the primary tumor residual intact component and other suspicious pigmented lesions, tumor satellites, in-transit metastases, and regional lymph nodes.
B
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Imaging for staging
Laboratory tests
Diagnostic procedures
Excisional biopsy: as per ESMO 2025 guidelines, perform a full-thickness complete excision with a minimal margin of clinically uninvolved skin for the diagnosis of CM.
B
consider performing a biopsy for larger lesions where complete excision is not possible without reconstructive surgery. B
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Sentinel lymph node biopsy
Molecular testing
Medical management
Management of melanoma in situ, wide-local excision: as per ESMO 2025 guidelines, perform full-depth wide-local excision of primary tumors with safety margins of 0.5 cm for in situ melanomas.
B
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Management of melanoma in situ (primary radiotherapy)
Management of melanoma in situ (topical therapy)
Management of locoregional disease (general principles)
Management of locoregional disease (neoadjuvant therapy)
Management of locoregional disease (wide-local excision)
Management of locoregional disease (management of in-transit metastases)
Management of locoregional disease (lymph node dissection)
Management of locoregional disease (adjuvant systemic therapy)
Management of locoregional disease (adjuvant radiotherapy)
Management of advanced/metastatic disease (general principles)
Management of advanced/metastatic disease (first-line therapy)
Management of advanced/metastatic disease (second-line therapy)
Management of advanced/metastatic disease (third-line therapy)
Management of advanced/metastatic disease (management of brain metastases)
Management of advanced/metastatic disease (management of extracranial metastases)
Concurrent use of exogenous hormones
Specific circumstances
Pregnant patients: as per AAD 2019 guidelines, ensure a tailored, multidisciplinary approach of care for pregnant patients with CM, involving obstetrician and CM specialist relevant to the patient's stage of disease. Recognize that the diagnosis of CM during pregnancy does not alter prognosis or outcome for the patient, however take the safety of the fetus into consideration for work-up and treatment.
E
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Patients with mucosal melanoma
Patients with vulvar melanoma
Patient education
General counseling
As per ESMO 2025 guidelines:
Advise patients with melanoma to avoid sunburn or unprotected solar or artificial UV exposure. Educate patients on the importance of lifelong regular self-examinations of the skin and peripheral lymph nodes.
B
Inform patients that family members have an increased risk of melanoma.
B
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Genetic counseling
Preventative measures
Primary prevention
As per USPSTF 2018 guidelines:
Counsel persons with fair skin types aged 6 months to 24 years and parents of young children about minimizing exposure to UV radiation to reduce the risk of skin cancer.
B
Offer counseling selectively in adults > 24 years with fair skin types about minimizing exposure to UV radiation to reduce the risk of skin cancer, taking into consideration the presence of risk factors for skin cancer.
B
Follow-up and surveillance
Assessment for cutaneous toxicity: as per AAD 2019 guidelines, ensure collaboration between dermatologists and oncologists for the management of cutaneous toxicity during BRAF/MEK kinase or immune checkpoint inhibitor therapy because appropriate recognition and control of skin side effects may improve the QoL of patients with CM and avoid unnecessary interruption of medication.
E
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Skin reconstruction after tumor resection (timing)
Skin reconstruction after tumor resection (perioperative antibiotics)
Skin reconstruction after tumor resection (perioperative antithrombotics)
Skin reconstruction after tumor resection (perioperative analgesics)
Skin reconstruction after tumor resection (follow-up)
Follow-up