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Actinic keratosis and squamous cell carcinoma

  • Lesion

Rough sun spots are early, precancerous changes. Some turn into squamous cell carcinoma, the second commonest skin cancer.

Updated

What it is

Actinic keratosis is keratinocyte dysplasia caused by chronic sun exposure, a precursor that may regress, persist or progress. Full-thickness dysplasia is squamous cell carcinoma in situ (Bowen disease), and invasion of the dermis is invasive squamous cell carcinoma. Cutaneous squamous carcinoma is usually curable by excision but metastasises more often than basal cell carcinoma, particularly in immunosuppressed patients.

Structure

  • Actinic keratosis: atypical basal keratinocytes, budding, parakeratosis with sparing of adnexal ostia, solar elastosis in the dermis.
  • SCC in situ: atypia at all levels, loss of maturation, intact basement membrane.
  • Invasive SCC: irregular nests and strands, keratin pearls, intercellular bridges; grade by differentiation.
  • Keratoacanthoma: symmetric cup-shaped lesion of glassy keratinocytes around a central keratin plug.

Step by step

  1. UVB causes pyrimidine dimers; failure to repair them (as in xeroderma pigmentosum) increases mutations.
  2. TP53 is mutated early; keratinocytes resist apoptosis and form clones.
  3. UV also suppresses skin immunity by impairing Langerhans cell function.
  4. Basal atypia (actinic keratosis) extends to full thickness (in situ carcinoma).
  5. Further mutations (NOTCH, CDKN2A, HRAS) allow invasion through the basement membrane.

Clinical notes

  • Transplant recipients develop many aggressive SCCs; HPV and immunosuppressive drugs add to UV.
  • Marjolin ulcer: SCC in a chronic burn scar or wound; aggressive.
  • Sun protection reduces actinic keratoses and SCC.

Test yourself

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

Which population has the greatest increase in cutaneous SCC risk?

Immunosuppressed organ transplant recipients.

What is the histologic definition of SCC in situ (Bowen disease)?

Full-thickness atypia of the epidermis with an intact basement membrane.

What is a Marjolin ulcer?

Squamous cell carcinoma arising in a chronic scar, burn or non-healing ulcer.

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

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Representative model, for educational purposes only.