Last updated: May 8, 2023

Summarytoggle arrow icon

Melanoma, a highly malignant tumor arising from melanocytes, is the most common life-threatening dermatological disease. Risk factors include UV radiation exposure, particularly in light-skinned individuals that are easily sunburned, increasing age, family history, and immunosuppression. The superficial spreading melanoma is the most common subtype. Other subtypes, such as nodular melanoma, have a significantly worse prognosis because they tend to metastasize more rapidly. Invasive melanoma is particular in its propensity to metastasize to unusual locations that are not commonly affected by other malignancies. Immediate full-thickness surgical biopsy of the primary tumor is usually the best initial diagnostic test and may be therapeutic for localized disease. Chemotherapy, biologics, and/or radiation therapy are recommended for recurrent or widespread disease. Tumor thickness is the most important prognostic factor.

Epidemiologytoggle arrow icon

Most common life-threatening dermatological disease


Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Clinical featurestoggle arrow icon


  • Pruritic, persistently bleeding skin lesion
  • Dermoscopy should be used to examine lesions for ABCDE criteria:
    • A = Asymmetry
    • B = Border (irregular border with indistinct margins)
    • C = Color (new changes in pigmentation or variations in pigmentation within the same lesion)
    • D = Diameter > 6 mm
    • E = Evolving (new lesion or a lesion that changes in size, shape, or color over time)

Types of melanoma

Overview of melanoma types [5]
Frequency and characteristic features Predilection sites Clinical appearance Growth

Superficial spreading melanoma

  • ∼ 60%
  • Back or chest (common in men)
  • Extremities (common in women)
  • Flat irregular tumor; sometimes with nodular segments
  • Variable pigmentation
  • Relatively prolonged horizontal growth .

Nodular melanoma

  • ∼ 20%
  • Fast growth in depth

Lentigo maligna melanoma

  • Sun-exposed skin areas (esp. face)
  • Large and irregularly shaped patch
  • Irregular pigmentation
  • Relatively slow horizontal growth

Acral lentiginous melanoma

  • ∼ 5%
  • More common in dark-skinned and Asian populations
  • Irregularly shaped, brown-black pigmented macule
  • Ulceration may occur
  • Hutchinson sign of the nail in subungual type: dark linear patch, widens with time, arising from the nail
  • Slow horizontal growth

Subtypes and variantstoggle arrow icon

Genitourinary melanoma (GU melanoma)

Overview [6]

  • 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 [6]

Overview of GU melanoma types
Characteristics Female genital melanoma Male genital melanoma Urological mucosal melanoma
  • Rare: ∼ 1% of all melanomas, 5% of vaginal malignancies [7][8]
  • >
  • Peak age of onset: 7th decade
  • Peak age of onset: 6th decade
  • Vulvar melanoma
  • Vaginal melanoma
  • Renal melanoma
  • Ureteral melanoma
  • Bladder melanoma
  • Urethral melanoma
Clinical features
  • Clinical presentation and histopathological confirmation
  • Surgical resection with an adequate margin


Diagnosticstoggle arrow icon

  • A full-thickness excisional biopsy (best diagnostic test) with 1–3 mm margins is indicated in all suspicious lesions. ; [9]
    • An excisional biopsy procedure used to obtain a tissue sample of skin that includes every layer (i.e., healthy and abnormal tissue)
    • A second resection may be necessary if the melanoma is histologically confirmed.
    • Pathology shows s100-protein positive, epithelioid cells with fine granules in cytoplasm
  • Staging tests (e.g., ultrasound or MRI) once diagnosis confirmed: to determine tumor thickness, spread to lymph nodes, or distant metastasis [10]

Complete excisional biopsies are always preferred over incisional biopsies, as they allow tumor thickness to be properly estimated!

Differential diagnosestoggle arrow icon

Differential diagnosis of common skin cancers
Color Morphology Location Other characteristic features
  • Brown, black (variable pigmentation)
  • Irregular macule, nodule, or patch
  • Anywhere
  • Commonly on trunk or extremities
  • Slow growth (rapid growth possible)
Cutaneous squamous cell carcinoma
  • Red
  • Sun exposed areas (e.g., typically lower lip)
  • “Rough” texture
  • Slow growth
  • All eventually ulcerate (everted edges, friable, inflamed)
Basal cell carcinoma
  • Pink
  • Pearly, nodular lesion
  • Sun exposed areas (e.g., typically upper lip, eyelid, nose)

Benign lesions commonly resemble melanomas and should be biopsied to rule out cancer (see “Benign skin lesions”).

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

  • Surgical excision: full-thickness excision with appropriate safety margins
    • 0.5–1 cm safety margin: melanoma in situ (T0)
    • Other margins according to Breslow depth: thickness from the granular layer to the lowest detectable tumor cell. The Breslow index correlates with the risk of metastasis.
Breslow classification of invasive melanoma
Breslow stage TNM stage Modified by AJCC Safety margin
I pT1 ≤ 1.0 mm 1 cm
II pT2 1.01–2 mm 1–2 cm
III pT3 2.01–4 mm 2 cm
IV pT4 ≥ 4 mm
If tumor thickness > 1 mm (Breslow stage ≥ II): perform sentinel lymph node biopsy

The gold standard is immediate, complete excision of the tumor.

Complicationstoggle arrow icon

Metastatic disease [13]

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

  • 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.
    • Regression

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Referencestoggle arrow icon

  1. Taylor R. Family Medicine: Principles and Practice. Springer Science & Business Media ; 2002
  2. Loescher LJ, Crist JD, Siaki LACL. Perceived intrafamily melanoma risk communication. Cancer Nurs. 2009; 32 (3): p.203-210.doi: 10.1097/ncc.0b013e31819ae11c . | Open in Read by QxMD
  3. Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Modern Pathology. 2017; 31 (1): p.24-38.doi: 10.1038/modpathol.2017.104 . | Open in Read by QxMD
  4. Aoude LG, Wadt KAW, Pritchard AL, Hayward NK. Genetics of familial melanoma: 20 years afterCDKN2A. Pigment Cell & Melanoma Research. 2015; 28 (2): p.148-160.doi: 10.1111/pcmr.12333 . | Open in Read by QxMD
  5. Carr MJ, Sun J, Spiess PE, Zager JS. Advances in the management of genitourinary melanomas. AME Medical Journal. 2019; 4: p.41-41.doi: 10.21037/amj.2019.11.03 . | Open in Read by QxMD
  6. Rapi V, Dogan A, Schultheis B, Hartmann F, Rezniczek GA, Tempfer CB. Melanoma of the Vagina: Case Report and Systematic Review of the Literature.. Anticancer Res. 2017; 37 (12): p.6911-6920.doi: 10.21873/anticanres.12155 . | Open in Read by QxMD
  7. Hou JY, Baptiste C, Hombalegowda RB, et al. Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma. Cancer. 2016; 123 (8): p.1333-1344.doi: 10.1002/cncr.30473 . | Open in Read by QxMD
  8. Melanoma of Nail Unit. Updated: January 1, 2011. Accessed: February 20, 2018.
  9. Swetter SM, Tsao H, Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2018; 80 (1): p.208-250.doi: 10.1016/j.jaad.2018.08.055 . | Open in Read by QxMD
  10. Garbe C, Peris K, Hauschild A, et al. Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline: Update 2016. Eur J Cancer. 2016; 63: p.201-217.doi: 10.1016/j.ejca.2016.05.005 . | Open in Read by QxMD
  11. Chapman PB, Hauschild A, Robert C, et al. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. N Engl J Med. 2011; 364 (26): p.2507-2516.doi: 10.1056/nejmoa1103782 . | Open in Read by QxMD
  12. $Immune Checkpoint Inhibitors in the Treatment of Melanoma: From Basic Science to Clinical Application.
  13. Zbytek B, Carlson JA, Granese J, Ross J, Mihm M, Slominski A. Current concepts of metastasis in melanoma. Expert Rev Dermatol. 2008; 3 (5): p.569-585.doi: 10.1586/17469872.3.5.569 . | Open in Read by QxMD
  14. Qu G, Kaur JS, Seward JB. Metastatic melanoma presenting as cardiac mass and hemobilia.. Am J Med Sci. 2003; 325 (3): p.157-159.
  15. Signs and Symptoms of Melanoma Skin Cancer. Updated: May 20, 2016. Accessed: March 11, 2017.
  16. What to look for: ABCDEs of melanoma. . Accessed: March 11, 2017.
  17. Melanoma (Malignant Melanoma). Updated: February 1, 2017. Accessed: February 20, 2018.

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