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Melanoma: subtypes, Breslow and markers

  • Lesion

Melanoma is diagnosed under the microscope, and its thickness in millimetres is the single most important predictor of outcome.

Updated

What it is

Clinically, melanoma is suspected by the ABCDE features: asymmetry, irregular border, colour variation, diameter and evolution. Histologically, it shows atypical melanocytes spreading as single cells up through the epidermis, lack of maturation and dermal mitoses. The report records subtype, Breslow thickness, ulceration, mitotic rate, margins, regression and lymphovascular invasion, which together drive staging and treatment.

Structure

  • In situ: atypical melanocytes in nests and single cells at the junction and in upper layers (pagetoid).
  • Invasive: dermal nests and sheets of large cells with large nuclei, prominent red nucleoli, mitoses, no maturation.
  • Cells may be epithelioid, spindled or small; pigment varies; amelanotic melanoma lacks it.
  • Host response: lymphocytes, and regression (fibrosis, melanophages) when the immune system destroys part of the tumour.
  • Hutchinson sign in acral melanoma: pigment spreading onto the nail fold.

Melanoma subtypes

SubtypeTypical site and patientGrowth
Superficial spreadingTrunk in men, legs in women; middle ageLong radial phase, then vertical
NodularAny siteVertical from the start; thick at diagnosis
Lentigo maligna melanomaSun-damaged face, older adultsVery long radial phase (lentigo maligna)
Acral lentiginousPalms, soles, nail beds; commonest in darker skinRadial then vertical; often diagnosed late
DesmoplasticSun-damaged head and neckSpindle cells in fibrous stroma, neurotropic

Markers

  • S100
  • SOX10
  • Melan-A (MART-1)
  • HMB-45
  • PRAME
  • Ki-67

Clinical notes

  • Spread: regional lymph nodes and in-transit metastases, then lung, liver, brain, almost anywhere; late recurrences are typical.
  • Melanoma is a great mimic in metastases; S100 and SOX10 settle the question.

Test yourself

Think of the answer, then tap the question to see it.

What is Breslow thickness?

The depth from the top of the granular layer (or ulcer base) to the deepest invasive melanoma cell; the main prognostic factor in localised melanoma.

Which melanoma subtype is most common on palms, soles and nail beds?

Acral lentiginous melanoma.

Which two markers are the most sensitive for melanoma?

S100 and SOX10.

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: Melanoma (MedlinePlus, US National Library of Medicine, 2025); Melanoma Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).

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Representative model, for educational purposes only.