Malignant melanoma

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.

1. Dummer R, Hauschild A, Lindenblatt N, Pentheroudakis G, Keilholz U, Committee EG. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26 Suppl 5:v126-32.
2. Larson AR, Rothschild B, Walls AC, et al. Impact of the 2009 AJCC staging guidelines for melanoma on the number of mitotic figures reported by dermatopathologists at one institution. J Cutan Pathol 2015;42:536-41.
3. Nathan P, Cohen V, Coupland S, et al. Uveal Melanoma UK National Guidelines. Eur J Cancer 2015;51:2404-12.
4. Watts CG, Dieng M, Morton RL, Mann GJ, Menzies SW, Cust AE. Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. Br J Dermatol 2015;172:33-47.
5. Pflugfelder et al. Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma". J Dtsch Dermatol Ges. 2013 Aug;11 Suppl 6:1-116, 1-126.