Cutaneous Squamous Cell Carcinoma

by Kesiree Naidoo | Apr 9, 2021

What is cutaneous squamous cell carcinoma?

Squamous cell carcinoma (SCC) is the second-most common form of skin cancer, originating from keratinocytes (skin cells). It is a form of non-melanoma skin cancer (NMSC).   

“SCC of the skin is also known as cutaneous squamous cell carcinoma (cSCC). Adding the word “cutaneous” identifies it as skin cancer and differentiates it from squamous cell cancers that can arise inside the body, in places like the mouth, throat or lungs.”

cSCC may originate in pre-existing actinic keratosis, which are rough, scaly patches on the skin caused by years of sun exposure. 

The danger of cSCC is that they can become invasive and spread (metastasis) to other organs, which could have worse consequences, including death. They should be identified and managed before the invasive stage.

Who gets cutaneous squamous cell carcinoma?

cSCC occurs particularly in elderly males who have had excessive cumulative or occupational sun exposure but can also occur in young people and women.

The below risk factors may increase your chance of getting cSCC:

  • People with fair skin who burn easily in the sun
  • People with red hair and freckles
  • A person with a history of skin cancer (previous NMSC or melanoma)
  • Excessive sun exposure
  • The use of tanning beds
  • Ionizing radiation
  • Exposure to chemicals such as arsenic
  • HPV infection

In addition, the below can also cause an increased risk of getting cSCC:

Predisposing genetic syndromes such as:

  • Xeroderma pigmentosum
  • Oculocutaneous albinism
  • Ferguson–Smith syndrome 

Predisposing skin conditions 

  • Chronic non-healing wounds or burn scar (the resulting SCC is a marjolin ulcer)
  • Patients that have porokeratosis 

Conditions of immunosuppression

  • Patients that have received organ transplantation and are on immunosuppressant medication
  • Patients with HIV 

What causes cSCC?

SCC occurs when the flat, thin squamous cells in the middle and outer layers of your skin develop changes (mutations) in their DNA.  

These mutations are mostly the result of damage caused by exposure to ultraviolet rays (UVA and UVB). However, certain medications, cigarette smoking and predisposing genetic syndromes can also cause DNA mutations. 

What does cutaneous squamous cell carcinoma look like?

cSCC typically appears as crusted, scaling nodules or a non-healing ulcer. They are normally found in sun-exposed areas, such as the scalp, the backs of your hands, your ears or your lips. However, they can be found anywhere, especially in those who are immunosuppressed or have genetic syndromes.

Signs of cSSC include:

  • A firm, red nodule
  • A flat sore with a scaly crust
  • A new sore or raised area on an old scar or ulcer
  • A rough, scaly patch on your lip that may evolve to an open sore
  • A red sore or rough patch inside your mouth
  • A red, raised patch or wart-like sore on or in the anus or on your genitals

What are the different types of squamous cell carcinoma?

There are four main types of squamous cell cancer:

  1. Bowens (SCC in situ)
    This SCC involves the entire thickness of the epidermis (skin) but does not invade beyond the basement membrane. The term ‘in situ’ added on tells us that this is a surface form of skin cancer. It appears as a well-demarcated, thickened area of skin that is usually pink in colour; however, it may also be pigmented. It can be treated with topical creams, PDT, or cryotherapy if small enough.
  2. Invasive SCC
    As it suggests, this form of SCC invades beyond the basement membrane and poses a risk for metastatic cancer. It may present as nodular, an ulcer or a crusted pink lesion. Invasion is usually only confirmed with histology (using a microscope to study the tissue structure).
  3. Keratoacanthoma
    This is a rapidly growing, well-differentiated tumour that appears like a volcano. It develops rapidly over six to eight weeks and spontaneously involutes. It can occur as a solitary tumour or multiple tumours in specific syndromes. Because they can’t be reliably distinguished from SCC by appearance alone, they need to be cut out for histology.
  4. Verrucous SCC
    This is well-differentiated cancer that develops in association with an HPV infection. It may appear large and warty and generally has a well-demarcated edge under a microscope.

What are considered to be risk factors for metastasis of invasive cutaneous SCC?

cSCC is classified as low-risk or high-risk depending on the chance of tumour reoccurrence and metastasis

cSCC is considered high-risk if the below characteristics are present:

  • Tumour thickness is over 2mm 
  • Diameter is greater than or equal to 2cm
  • Location on the ear, lips, tongue, vulva or penis 
  • Arising within a scar (for example, a burn scar or site of previous radiation treatment)
  • The tumour is poorly differentiated or undifferentiated under a microscope
  • Arising in elderly or immune-suppressed patients (for example, organ transplant recipients or patients with HIV)

How is cSCC diagnosed?

The diagnosis of cutaneous SCC is based on clinical features and is confirmed by biopsy or excision and histology.

Those patients at risk for metastatic SCC may need further investigation, including ultrasound, x-rays, CT scans, and other biopsies as deemed appropriate.

What is the treatment for cSCC? 

Cutaneous SCC is almost always treated surgically, using an excision with a clear margin in most cases. 

Other methods of removal can include:

  • Curette and cautery (where it is scraped off and heat is applied to the skin’s surface) 
  • Cryotherapy with liquid nitrogen may be used in some low-risk lesions of SCC in situ
  • SCC in situ (or Bowen’s) may be treated with three cycles of PDT or topical chemotherapy
  • SCC that can’t be excised may also be treated with radiotherapy in special circumstances.

Most SCCs can be treated and cured if the treatment is undertaken when the lesion is small. However, about 50% of people with a high risk of SCC develop a second one within 5 years of the first. It is therefore very important to do regular self-examinations of the skin and annual checkups with your dermatologist. 

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