Melanoma, a malignancy arising from melanocytes, is the most common cause of skin cancer-related death. Risk factors include UV radiation exposure (especially in individuals with light skin), dysplastic nevi, a family history of melanoma, and immunosuppression. Melanoma is most commonly cutaneous in origin, but may also arise in mucosal surfaces and in the uvea. There are four main histological subtypes of melanoma. Superficial spreading melanoma is the most common, while nodular melanoma tends to grow rapidly in depth and has the worst prognosis of all the subtypes. Clinical features concerning for melanoma include asymmetry, border irregularity, color variegation, diameter > 6 mm, and evolving size, shape, and/or color over time (i.e., the ABCDE criteria). Full-thickness excisional biopsy of skin lesions is the best diagnostic test for melanoma and should be performed immediately in all patients with suspicious lesions. Additional diagnostic and staging tests (e.g., sentinel lymph node biopsy and/or imaging) may be indicated in certain patients. Tumor thickness is a key prognostic factor. Treatment is primarily surgical and includes wide excision of the lesion with surgical margins determined by the tumor thickness. Systemic drug therapy (e.g., with immune checkpoint inhibitors, BRAF inhibitors, and MEK inhibitors) or radiation therapy may be indicated in patients with metastatic or unresectable disease.
Risk factors for cutaneous melanoma 
- UV radiation exposure (e.g., nonadherence to , previous episodes of sunburn, use of tanning beds) 
- Light skin types 
- Precursor lesions, including: 
- Personal or family history of melanoma or other skin cancer 
- Predisposing inherited skin conditions (e.g., xeroderma pigmentosum, familial atypical multiple mole melanoma syndrome)
- Genetic mutations, including:
ABCDE criteria 
The following skin lesion characteristics are concerning for melanoma:
- A = Asymmetry
- B = Border (irregular border with indistinct margins)
- C = Color (variegated pigmentation within the same lesion)
- D = Diameter > 6 mm
- E = Evolving (a lesion that changes in size, shape, or color over time)
Other signs and symptoms 
By site of origin 
- Cutaneous melanoma originates from melanocytes in the epidermis.
- Noncutaneous melanoma (much less common)
By histology 
Both cutaneous melanomas and mucosal melanomas may be categorized by these subtypes.
|Histological subtypes of melanoma |
|Epidemiology||Typical sites||Clinical appearance||Growth|
Superficial spreading melanoma
| || || || |
| || || |
Lentigo maligna melanoma
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Acral lentiginous melanoma
| || || |
Amelanotic melanoma 
- Any of the other histological subtypes may present; , less commonly, as amelanotic melanoma.
- Melanocytes in the lesion produce little to no pigment, causing the color to range from skin-colored to bright pink or red. 
- Diagnosis typically requires histological confirmation.
Genitourinary melanoma (GU melanoma) 
- Rare (< 5%)
- Approx. 45% of all mucosal melanomas
- Most commonly affects female individuals (approx. 90%)
- Cause remains unknown.
- Expression of cell biomarkers such as PD-1 and PD-L1 in vulvar melanoma is significantly higher than in cutaneous melanomas.
- Prognosis is generally poor.
Types of GU melanoma
|Overview of GU melanoma types|
|Characteristics||Female genital melanoma||Male genital melanoma||Urological mucosal melanoma|
|Epidemiology|| || |
|Classification|| || |
|Treatment|| || |
Subungual melanoma 
- Rare subtype of cutaneous acral lentiginous melanoma that develops within the nail unit
- Commonly manifests as (a brown to black longitudinal band), with additional features suggestive of malignancy:
- Individuals with suspicious skin lesion(s)
- Individuals with biopsy-confirmed melanoma: See “Melanoma staging.”
Skin biopsy 
- Full-thickness excisional biopsy: preferred method for all suspicious lesions 
- Incisional (partial) biopsy
Excisional biopsy of suspected melanoma should encompass the full depth of the lesion, as lesion depth is important for staging and prognostic purposes. 
- Atypical melanocytes may be: 
- Negative prognostic features
- Immunohistochemistry may be obtained in select cases.
Determination of stage
- Perform a comprehensive clinical evaluation, including:
- Obtain additional studies as needed for melanoma staging, e.g.:
Sentinel lymph node biopsy (SLNB) 
SLNB is recommended in certain patients, after careful discussion of risks and benefits and with the involvement of surgical oncology.
- Offer SLNB for cutaneous melanoma ≥ 1 mm in depth.
Consider SLNB for cutaneous melanoma that is:
- 0.8–1.0 mm in depth
- < 0.8 mm in depth with concerning features 
Additional studies 
- Not routinely recommended in asymptomatic patients with stage II melanoma or lower
- Indicated to evaluate for metastasis in select patients, e.g., with:
- May include:
Melanoma is staged using the American Joint Committee for Cancer (AJCC) system.
|AJCC staging of cutaneous melanoma (2018) |
|Tumor characteristics (T)||Regional spread (N)||Distant metastasis (M)|
|Stage 0 melanoma|| || |
|Stage I melanoma|
|Stage II melanoma|
|Stage III melanoma|| || |
|Stage IV melanoma|| || || |
Benign skin lesions 
These may include:
- Irritated benign
biopsy should be performed to rule out melanoma.  can resemble melanomas;
These may include:
Other skin cancers 
|Overview of common skin cancers |
|Cutaneous melanoma ||(BCC) |
|Color|| || || |
|Location|| || |
|Other characteristic features|
The differential diagnoses listed here are not exhaustive.
- Establish multidisciplinary cancer care, including referrals to specialists (e.g., dermatology, surgery, oncology, and/or radiation oncology) for:
- Ensure regular follow-up care for melanoma based on disease stage.
- Educate patients on: 
Wide local excision 
- Indicated for nearly all patients 
- Excision should be performed with surgical margins determined by the Breslow depth.
|Recommended surgical margins for invasive melanoma resection|
|Breslow depth||Surgical margin|
≤ 1 mm
> 1 mm and ≤ 2 mm
> 2 mm
First-line treatment for melanoma is prompt, complete excision of the tumor. 
Medical therapy for melanoma 
Systemic drug therapy
Regimens may include either or both of the following therapies:
- Immune checkpoint inhibitor combination therapy, e.g.:
- Targeted combination therapy in patients with BRAF mutations, e.g.:
- Adverse effects
- Lentigo maligna melanoma in situ that cannot be resected may be treated with:
- Metastatic disease may be treated with radiation therapy for palliation or if systemic therapy cannot be used. 
Follow-up care for melanoma 
- All patients should have lifelong follow-up with a dermatologist, focusing on:
- Monitoring for melanoma recurrence
- Screening for new primary melanoma
- Tailor frequency of visits to disease stage, e.g., as shown in the table below.
|Follow-up dermatologic examination schedule for cutaneous melanoma |
|Stage 0 melanoma|| |
|Stage I melanoma and stage IIA melanoma|| |
|Stage IIB melanoma and higher|| |
Suveillance imaging to detect occult metastasis may be performed in select patients for up to 3–5 years after diagnosis.
- Lymph node ultrasound surveillance is recommended if:
- Other modalities
Metastatic disease 
- Metastatic melanoma may spread to lymph nodes, liver, lung, brain, and bone
- May also metastasize to locations not typically affected by metastatic malignancies 
- Up to 5% of metastatic cases have no known primary tumor.
- Characteristic black pigmentation
We list the most important complications. The selection is not exhaustive.
Negative prognostic factors
- Epidemiological features: male sex
- Clinical features: type , localization , and presence of ulcerations
- Melanoma has a significant risk of metastasis, which is associated with a poorer prognosis.
- Tumor thickness, as determined from the Breslow thickness, is the most important prognostic factor.
Primary prevention 
- Provide advice on the importance of minimizing UV radiation exposure to reduce the risk of melanoma, including:
- Adherence to
- Avoidance of other sources of UV radiation exposure (e.g., tanning beds)
- The USPSTF specifically recommends providing advice to individuals who have light skin and are: 
- ≤ 24 years of age
- > 24 years of age with risk factors for cutaneous melanoma