Skin Cancers

 

• Risk factors

  Sun exposure

  UV rays from the sun cause most cases of skin cancer. A simple mnemonic is that UVA Ages (and tans, hence its use in sunbeds) and UVB Burns and causes cancer. However, it is likely that UVA also plays some role in causing cancer.

  Sources of UV exposure:

  • Outdoor work.
  • Living/working abroad.
  • Sunbeds
  • Frequent holidays.
  • Childhood sunburn is particularly a risk factor for BCC and malignant melanoma.

  Patient factors:

  • White people – skin types 1 (never tan) and 2 (occasionally tan) – are at highest risk.

  Immunosuppression

  • Post-transplant. Especially a risk factor for SCC.
  • Haematological disease.
  • HIV
  • Rheumatology treatment.

• Malignant melanoma

  Pathophysiology and types

  • Malignant proliferation of melanocytes, usually due to UV damage. Most feature mutations in BRAF, a Raf kinase that helps regulate cell division.
  • Melanoma can develop in existing moles, especially dysplastic naevi, or are entirely new lesions. Individuals with more moles are at higher risk.
  • Melanoma confined to the epidermis is 'melanoma in situ'; it can be excised without any further treatment, and is not life-threatening. Invasive melanomas are those that have spread to the dermis.
  • Superficial spreading melanoma is the commonest type, while nodular melanoma is the most aggressive, is more likely to be invasive, and seems to be unrelated to sun exposure.

  Epidemiology

  • Annual incidence: 1/10,000 in UK. Doubled in last 10 years.
  • Commoner in women, with median onset age 50.

  Signs

  A key challenge is to distinguish a melanoma from a mole. General signs of concerns:

  • Change in size, shape, or colour.
  • Irregular or asymmetrical.
  • First appear in later life (over 30).

  ABCDE criteria:

  • Asymmetry
  • Border irregularity.
  • Colour variation.
  • Diameter: ≥7 mm.
  • Evolving: enlarging or changing.

  7-point checklist:

  • Major features (2 points each): change in size (vertical or horizontal), shape, or colour.
  • Minor features (1 point each): inflammation, crusting, bleeding, altered sensation, ≥7 mm diameter.
  • ≥3 points are grounds for urgent referral and investigation.

  Common sites:

  • Back (males).
  • Legs (females).
  • But can occur anywhere.

  Management

  • Excision biopsy of any suspicious mole, with at least 1 cm margin. Don't bother with punch biopsy, due to the risk of sampling error. However, if the probability of malignancy is very low, a smaller margin than 1 cm can initially be used.
  • Breslow thickness classifies invasive melanoma. <1 mm has >90% 5yr survival, but >4 mm has around 50%. Overall, around 80% 5yr survival for all invasive melanoma.
  • Sentinel node biopsy if ≥1 mm thick, and remove any affected nodes (± other local nodes).
  • Nodal or systemic metastatic disease: immunotherapy – ipilimumab, nivolumab, pembrolizumab – and/or targeted therapy – dabrafenib, vemurafenib.

• Squamous cell carcinoma (SCC)

  Pathophysiology

  • Malignant proliferation of keratinocytes (squamous cells).
  • Most remain localized, but 5% metastasize, usually to lymph nodes.
  • Marjolin's ulcer is a rare SCC sub-type which arises within existing ulcers or chronically damage skin.
  • In addition to sun exposure and immunosuppression, xeroderma pigmentosum is a risk factor.

  Pre-malignant lesions

  Most SCCs arise within actinic keratosis. Although Bowen's disease has a higher risk of invasive transformation, it is much less common.

  Actinic keratosis (aka solar keratosis)

  • Thick, rough, adherent, scaly, red-yellow or skin-coloured lesions on sun-exposed sites.
  • Proliferation of atypical keratinocytes.
  • Variants include 'actinic cheilitis' – when on the lips – or 'cutaneous horns', which can also be caused by seborrheic keratosis and HPV, or even be a type of SCC.
  • Affects 1/3 people >60 years old.
  • Most are harmless and can be left alone, but individuals with more than 10 have a 10% risk of developing SCC. Biopsy any lesions which raise suspicion of malignancy, namely those that are large (>1 cm), thick, growing, bleeding, or painful.
  • Removal can be for pre-malignancy or cosmesis: cryotherapy for 1-2 lesions, 5-fluorouracil (5FU) if there are more.

  Bowen's disease

  • SCC in situ – i.e. intraepidermal – 1/30 of which will become invasive SCC.
  • Well-defined, red or pink, scaly plaque or patch, usually on lower leg.
  • In addition to sun exposure, HPV may play a causal role.
  • All should be removed, usually with cryotherapy or 5FU. Initial biopsy is only required if there is diagnostic uncertainty.

  Epidemiology

  • Annual incidence: 1/4000 in UK. Rarer than BCC, but in transplant patients it is the opposite: SCC is commoner.
  • 50% increase in last 10 years.

  Signs

  • Ulcerated, irregular lesion, with hard raised edge. May be painful.
  • Increases in size over months.
  • Found on sun-exposed sites. Those on lower lip are often linked to smoking.

  Management

  • Surgical excision with 4 mm margin.
  • Consider topical imiquimod or 5FU if superficial.

  Prognsis and complications

  • 20% have 2nd SCC in 3 years.
  • Prognosis is excellent, except in the rare case of metastatic disease, which has a 20% 10 year survival.
  • Features which increase the risk of metastasis: >2 cm size, >4 mm depth, poorly differentiated, immunosuppressed, certain sites (ear, lip, in ulcer).

• Basal cell carcinoma (BCC)

  Pathophysiology

  • Arises from keratinocytes in basal layer of epidermis.
  • Commonest but least dangerous skin cancer.
  • Aka 'rodent ulcer', as they burrow through tissue causing local damage, but almost never metastasize.
  • Classification: nodular (commonest), cystic, superficial spreading (usually on trunk), morphoeic (rare), pigmented.

  Epidemiology

  • Incidence 1/1000 per year in UK.
  • 50% increase in last 10 years.

  Signs

  • Shiny nodule ('pearly') with rolled, red ('telangiectatic') edge and eroded centre.
  • Slowly increases in size.
  • Usually on sun-exposed sites, especially upper ⅔ of face.

  Management

  Excision biopsy with 4 mm margin is the gold standard.

  Alternatives include:

  • Mohs' micrographic surgery, in which segments are excised in stages and examined histologically. Consider for difficult sites where tissue preservation is important e.g. eyelid.
  • Curettage – removal of tumour soft tissue – and cautery of the base. Consider for small BCCs (<1 cm), but downside is that margins are difficult to assess.
  • Topical cryotherapy or medication (5-fluorouracil, imiquimod). Incisional biopsy is still needed to confirm the diagnosis. Higher recurrence rates than surgery.
  • Radiotherapy. An alternative or adjunct to surgery. Good cure rate but may have poor cosmetic outcome.

  Complications and prognosis

  • Excellent prognosis.
  • However, 50% have 2nd BCC (other site) within 5 years.

• Benign sun damage

  • Structural: wrinkles.
  • Pigment: lentigines, mottled pigmentation.
  • Vascular: bruises/purpura, telangiectasia.
  • Solar elastosis: thick, wrinkled, yellow-brown skin.