Malignant melanoma

Last Updated: 2021-06-28

Author(s): Anzengruber F., Navarini A.

ICD11: 2C30.Z

Black skin cancer, melanoma, melanoma, malignant melanoma.

Malignant epithelial tumor of the melanocytes. 

  • Classification
    • Superficially spreading malignant melanoma (SSM).
    • Nodular (nodular) malignant melanoma (NM).
    • Acrolentiginal malignant melanoma (ALM).
    • Lentigo maligna melanoma (LMM).
    • Mucosal melanomas.
    • Amelanotic malignant melanomas. CAVE: Any type of melanoma may appear amelanotic.
    • Desmoplastic malignant melanoma.
    • Malignant melanoma with unknown primary tumor.
    • Occult primary localization (uvea, meninges, GI tract, lymph nodes).
  • Immunohistology 
    • Routine diagnostics: S100, MART1 and IMP3. 
    • Most important marker: MART1 (Melan A). 
    • Proliferation marker: MIB1. 
    • CD10 overexpression may be an indication of a worse prognosis. 

  • Incidence (Central Europe): 3-5/100'000/year. 
  • Incidence (Scandinavia): 12-15/100'000/year. 
  • Incidence (Australia): 40/100'000/year. 
  • Lifetime risk (2010) 1:75. 
  • The closer you live to the equator, the higher the incidence (for Caucasians). 
  • African Americans have a 20 times lower risk. 
  • Approximately 1.3% of all cancer deaths die due to a malignant melanoma. 
  • Women > Men. 

  • Superficially spreading malignant melanoma (SSM). 
  • Nodular (nodular) malignant melanoma (NM). 
  • Acrolentiginal malignant melanoma (ALM). 
  • Lentigo maligna melanoma (LMM). 
  • Mucosal melanomas. 
  • Amelanotic malignant melanomas. CAVE: Any type of melanoma may appear amelanotic. 
  • Desmoplastic malignant melanoma. 
  • Malignant melanoma with unknown primary tumor. 
  • Occult primary localization (uvea, meninges, GI tract, lymph nodes).

  • Risk factors 
  • Melanoma in the own anamnesis. 
  • UV radiation (cumulative sun exposure and sunburn). 
  • Light skin type (slight redness, severe tanning). 
  • Red hair (4.7-fold increased risk compared to black hairs). 
  • Positive family history. 
  • > 100 melanocytic nevi. 
  • ≥5 atypical nevus cell nevi, if ≥2 1st degree relatives have a melanoma. 
  • Dysplastic nevus syndrome (>5 atypical nevus cell nevi and > 50 inconspicuous nevus cell nevi).  
  • MDM2-SNP309 polymorphism. 
  • BK-mole syndrome. 
  • Xeroderma pigmentosum. 
  • An association with Parkinson's disease is discussed. 
  • Approx. 1/3 of all melanomas develop on existing nevus cell nevi. The majority of all melanomas develop de novo. 

  • Predilection sites 
    • Women: Face, lower leg.
    • Men: upper torso.
  • Partly reddish, partly bluish, sometimes brown-blackish or non-pigmented, inhomogeneous, mostly size-progressive, irregularly limited knots or plaques. 
  • Metastasis: occurs in 2/3 of all cases first lymphogenically and then haematogenically. However, haematogenic first metastases are also possible.  
  • Satellite metastases: reddish to skin-colored nodes grouped up to 2 cm around the primary tumor. 
  • In-transit metastases: Cutaneous or subcutaneous metastases located between the primary tumor and the locoregional lymph nodes.   
  • Haematogenic metastases can occur in all organs, especially the lungs, liver, heart, brain, skin or bone.

  • Anamnesis (own anamnesis, family anamnesis, sunburn?)
  • Clinic (ABCDE, ugly duckling concept). Full body inspection incl. mucous membranes, lymph node status!
  • Dermatoscopy.
  • Excision (although there is no data for the sowing of melanoma cells by biopsy, a complete excision of a biopsy is recommended). A safety distance of 2 mm is recommended.  Flat excisions should be avoided.
  • Mutation analyses: BRAF (V600E, V600K, approx. 40-60% of all tumors are BRAF mutated), NRAS, c-Kit (15% of mucosal or acrolentiginous melanomas are c-Kit pos.) and GNA11 or GNAQ (in uveal melanoma).
  • Tumor markers: S-100, LDH, possibly MIA (melanoma inhibitory activity). They are not useful for diagnosis, but only for follow-up.
  • S-100 should always be determined initially.
  • LDH should be determined in patients with suspicion/detection of distant metastases.
  • The diagnostic benefit of MIA has not yet been fully proven.
  • Postexcision
  • SLNB and/or staging, if applicable --> SOP currently being updated.

  • Classification according to WHO classification.
  • The assessment is made:
  • Anatomical localization.
  • Type of growth (superficially spreading, nodular MM, LMM).
  • Tumour thickness according to Breslow.
  • Clark Level.
  • I: Intraepidermal.
  • II: Cells in St. Papillare.
  • III: Tumor seeding in the St. Papillare.
  • IV: Medium/deep dermis.
  • V: Subcutis.
  • Ulceration.
  • Mitosis rate.
  • Characteristics are for example:

Asymmetric structure with atypical and necrotic, large and round melanocytes with light cytoplasm. Mitoses. Invasive growth in other structures.


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