2: Squamous Cell Carcinoma

Squamous cell carcinoma of the skin is the second most common malignancy in humans. Squamous cell carcinoma in situ is known as Bowen's disease. Dysplasia of the epithelium is known as actinic keratosis.


Squamous cell carcinoma occurs most frequently in Australia with an incidence of 166/100,000 people. It is more common in those of fair skin. The incidence is 3-5 times less than basal cell carcinoma.

Aetiology and Pathogenesis

Exposure to ultraviolet light is the most important risk factor. Mutations are caused by induction of pyrimidine dimers, although a different group of genes is mutated in SCC compared to BCC (typically k-RAS and CDK4). Unlike melanoma, frequent and chronic UV exposure is more important rather than episodes of childhood exposure and sunburn.
Other factors that can induce squamous cell carcinoma, albeit with far less numbers on a population level, include:

  • Ionising radiation exposure
  • Arsenic
  • Other industrial carcinogens
  • Significant skin trauma (burns, chronic ulcers)
  • HPV infection
  • Smoking (particularly for SCC of the lip)
  • Immunosuppression

Natural History

SCCs are typically locally aggressive but can spread to lymph nodes. This risk is raised when:

  • Lesions occur in high risk areas (lip, nose, ear, nasolabial fold)
  • The lesion is large (> 2 cm) or deeply invasive (> 5 mm)
  • The tumour is poorly differentiated
  • Perineural invasion is present
  • The patient is immunosuppressed
  • The tumour occurs in non-sun damaged skin (eg. genital area)

Patients should have their neck evaluated radiologically as well as clinically if the above risks are present.
Distant metastases can also occur, although lymphatic spread is usually occurs first.

Precursor Lesions

Acinitic keratosis is a collection of dysplasias of the skin epithelium. It is strongly associated with chronic sun exposure and is usually seen in sun exposed areas; lesions are usually erythematous, raised, hyperkeratotic and multiple. Patients are typically treated with cyrotherapy. There is a 5-10% risk of progression to SCC at 10 years, although this is much higher for patients with multiple lesions.
Bowen's disease is squamous cell carcinoma in situ and is similar to SCC in situ at other sites. It can occur in the genital region (usually in combination with HPV infection) or can occur at other sites. Bowen's disease can progress to invasive disease with a risk of about 10%.

Clinical Presentation

Patients usually present with an ulcerated, hyperkeratotic, growing mass on the skin. Some lesions may be depressed ulcers whereas others may not show ulceration or hyperkeratosis; biopsy is essential.
Examination will frequently demonstrate sun damaged skin and actinic keratosis or Bowen's disease may be present. Lymphadenopathy should be checked for as lymph node metastases may be present particularly in high risk areas (face, scalp, genitals).

Tumour/Normal Tissue Features

Squamous Cell Carcinoma

Other Types

Acantholytic SCC

Spindle Cell SCC

Verrucous SCC

Staging / Classification

TNM or other staging system if relevant