Cutaneous Squamous Cell Carcinoma (SCC)

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Introduction

Cutaneous squamous cell carcinoma (SCC), a form of non-melanoma skin cancer (NMSC), is the second most common type of skin cancer in the UK, following basal cell carcinoma.1Β 

Incidence rates are outdated and underreported, however, from 2013 to 2015 the incidence rate of primary SCC in England was thought to be 77.3 per 100,000 person-years in men and 34.1 per 100,000 person-years in women.2

You might also be interested in our medical flashcard collection which contains over 1000 flashcards that cover key medical topics.

Aetiology

In SCC, cancerous mutations occur in squamous keratinocytes in the epidermis, the outermost layer of the skin.3 There are three layers of the skin: the epidermis, dermis and subcutaneous layer (hypodermis).

Within the epidermis, there are five layers: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum and stratum basale. The squamous keratinocytes lie above the stratum basale in the stratum spinosum.4

Ultraviolet exposure (specifically UVB rays) is the main cause of SCC.7Β  Chronic UV exposure will damage the DNA of the squamous keratinocytes, leading to tumour formation.8 Signature mutations include the p53 tumour suppressor gene.9


Risk factors

Risk factors for SCC include:8

  • Ultraviolet radiation
  • Immunosuppression
  • Fitzpatrick skin types I and II (fairer skin)Β 
  • Solid organ transplant recipientsΒ 
  • Increasing age
  • Male sex
  • Ionising radiation
  • Sites of chronic inflammation

SCC is the most common skin cancer in Fitzpatrick skin types V and VI (brown and black skin).8


Clinical features

History

Typical symptoms of an SCC may include:10

  • Skin changes (e.g. growing nodule, bleeding lesion, texture or colour change, ulceration, pain)
  • Red flags for cancer (e.g. malaise, weight loss)
  • Lymphadenopathy

Other important areas to cover in the history include:

  • Ultraviolet risk: sun exposure and use of sun protection
  • Systemic enquiry: red flags for cancer (e.g. malaise, weight loss)
  • Past medical history: skin cancer, immunosuppression, Bowen’s disease, actinic keratosis and solid organ transplant recipients
  • Family history: implies skin type, genetic tendency and sun exposure
  • Social history: outdoors occupation, hobbies and tanning/use of sunbeds
  • Travel history: chronic sun exposure

For more information, see the Geeky Medics guide to dermatological history taking.Β 

Clinical examination

Characteristic features of SCC lesions include bleeding, itching and crusting and these lesions will typically appear in sun-exposed areas (e.g. the lips, back of the hands and upper part of the face or scalp).8,11

Other features of sun damage may be present near the lesion including:8,9

  • Age spots (solar lentigines)
  • Sunburn or sun tan
  • Excessive wrinkling caused by solar elastosis (age-related UV damage)
  • Actinic keratosis (pre-malignant lesions induced by UV damage)
Morphology SCC lesions

Typical features of a cutaneous squamous cell carcinoma include:11

  • Firm to palpate (may be nodular/plaque-like)
  • May ulcerate and bleed
  • May be tender/painful
  • May have a crusty (keratotic) top with a nodular base
  • Size is variable

For more information, see the Geeky Medics guide to examining a non-pigmented skin lesion.

Squamous cell carcinoma on the cheek
Figure 3. A SCC on the cheek.12

Dermatoscopy

A dermatoscope is a tool used to evaluate skin lesions by magnifying the lesion.13Β  In the context of SSCs it can be used to aid diagnosis and help distinguish between a SCC and a BCC.14

Bowen’s disease

Bowen’s disease (also known as SCC in situ) occurs when the cancerous cells are confined to the epidermis.15Β It can also progress into invasive SCC, so it is important to monitor and treat Bowen’s disease promptly.

Bowen’s disease lesion on the cheek
Figure 4. Bowen’s disease lesion on the cheek.16

Actinic keratosis

Actinic keratosis involves the formation of precancerous scaly lesions on the skin.17Β Actinic keratoses have around a 10% risk of developing into an SCC, therefore monitoring and treatment are important.18

Multiple actinic keratoses lesions on the scalp
Figure 5. Multiple actinic keratoses lesions on the scalp.19

Both these conditions have similar risk factors to SCC (e.g. chronic UV exposure and Fitzpatrick skin types I and II).

Representative images of diverse skin types

Because of image reproduction rules, we are only able to directly include images with creative commons licencing. Unfortunately, the majority of images of dermatological conditions available under this licence are of Caucasian patients and fair skin tones.

We have included representative images here that we are not able to reproduce in this article directly, which we encourage you to review:


Differential diagnoses

Possible differential diagnoses in the context of suspected SCC include:8

  • Actinic keratosis
  • Basal cell carcinoma
  • Seborrhoeic keratosis

Investigations

The first line investigation for a suspected SCC is a biopsy.8 This may comprise an excisional, punch or incisional biopsy so the lesion can be examined histologically.20

Excisional or shave biopsy to remove the whole lesion is used if the lesion is small, in an accessible area, not present in a cosmetically sensitive area and not near vital structures, so it can all be removed in one go.20

Incisional/punch biopsy which samples only a small (usually 4mm) part of the lesion is used if the lesion is large, in an inaccessible area, present in a cosmetically sensitive area or near vital structures, to confirm the diagnosis and allow planning of further treatment if required.20

Other relevant investigations may include ultrasound of lymph nodes, CT and MRI for staging or if metastasis is suspected.8

 


Diagnosis

Various classification systems exist for SCC, which include:8

  • Histopathological
  • Clinicopathological
  • Border’s classification

Staging

The American Joint Commission on Cancer (AJCC) TNM system is commonly used to stage SCC.23Β They are broadly categorised as either low risk or high risk, which helps to direct appropriate management.

High-risk features include:

  • Size: >2mm deep or >20mm wide
  • Site: face, ear, genitals, hands, feet
  • Recurrence
  • Immunosuppressed individual
  • Poor differentiation (histologically)
  • Perineural invasion (histologically)
  • High tumour budding


Management

NICE suggests a 2-week wait (2WW) referral for potential SCCs to a skin cancer screening clinic.24

Treatments range from cryotherapy, surgical excision, surgical curettage and cautery, Mohs micrographic surgery and radiotherapy and will depend on various factors including the patient’s medical history (e.g. comorbidities), location of the lesion and TNM staging.8

Bowen’s disease (SCC in situ)

For Bowen’s disease, destructive therapies such as cryotherapy or topical therapies like 5-fluorouracil are first-line management.8

Cryotherapy, a form of non-surgical destruction, commonly uses liquid nitrogen to freeze the skin lesion.25Β Topical 5-fluorouracil, a chemotherapeutic agent, targets the cancerous cells and leads to the resolution of the skin lesion.8

Invasive SCC

For invasive SCC (i.e, SCC growing beyond the epidermis), first-line treatment consists of conventional surgical excisionΒ with a minimum of 4mm margins.8

If the SCC is present in a cosmetically sensitive location like the face, then Mohs micrographic surgery, also known as also margin-controlled excision, is the preferred treatment option.8,25

Metastatic SCC

For metastatic SCC, first-line treatment may consist of surgical excision, radiotherapy and chemotherapy.8Β New immunotherapy drugs are also now available for certain cases, for example, immune checkpoint inhibitors.27

Prevention

Primary and secondary prevention includes the usage of broad-spectrum sun creams with UV-A and UV-B coverage, physical sun protection, avoidance of the sun and discouraging the use of sunbeds.8,28


Complications

Complications of surgical management of SCC may include:8,29

  • Bleeding
  • Post-operative infection
  • Pain
  • Scarring (including keloid)
  • Nerve damage
  • Physical deformities

Key points

  • Cutaneous squamous cell carcinoma (SCC) occurs when there is a cancerous mutation of the squamous keratinocytesΒ in theΒ epidermis.
  • SCC is the second most common type ofΒ skin cancer in the UK, following basal cell carcinoma.
  • The most common cause of SCC is chronic UV exposure
  • SCC lesions may bleed, itch and crust and are firm on palpation
  • Skin biopsy is the first line investigation. Other relevant investigations include ultrasound of lymph nodes, CT and MRI (for staging).Β 
  • Medical management for non-invasive SCC may include topical therapies (e.g. 5-fluorouracil)
  • Surgical management for SSC may include cryotherapy, surgical excision, and Mohs micrographic surgery
  • Primary and secondary prevention includes the usage of sun creams with UV-A and UV-B spectrum coverage, physical sun protection, avoidance of sun and discouraging the use of sunbeds

Reviewer

Dr Natalya Fox

Dermatology Registrar


Editor

Dr Chris Jefferies


References

  1. British Skin Foundation. Squamous cell carcinoma. N.D. Available from: [LINK]
  2. Venables et al. Nationwide incidence of metastatic cutaneous squamous cell carcinoma in England. 2019. Available from [LINK]
  3. American Academy of Dermatology. Skin cancer types: Squamous cell carcinoma. N.D. Available from [LINK]
  4. National Cancer Institute.Layers of the skin.Β N.D. Available from [LINK]
  5. Gordon Betts et al. Structure of the skin. License: [CC BY 3.0]. Available from: [LINK]
  6. J. Gordon Betts et al. Layers of the epidermis. License: [CC BY 3.0]. Available from: [LINK]
  7. Kripe. Immunological effects of ultraviolet radiation. 1991. Available from [LINK]
  8. BMJ. Squamous cell carcinoma of the skin. N.D Available from [LINK]
  9. DermNet NZ. Cutaneous squamous cell carcinoma. N.D. Available from [LINK]
  10. Cleveland clinic. Β Squamous cell carcinoma. N.D. Available from [LINK]
  11. The Primary Care Dermatology Society. Β Squamous cell carcinoma. N.D. Available from [LINK]
  12. Dermanonymous. Squamous Cell Carcinoma, Right Upper Cheek. License: [CC BY-SA 4.0]. Available from [LINK]
  13. American Family Physician. Dermoscopy: An Invaluable Tool for Evaluating Skin Lesions.2008. Available from [LINK]
  14. DermNet NZ. Dermoscopy of squamous cell carcinoma. 2008. Available from [LINK]
  15. Skinhealthinfo.org. Bowen’s disease (squamous cell carcinoma in situ). N.D. Available from: [LINK]
  16. Klaus et al. Bowen. License [CC BY 3.0]. Available from [LINK]
  17. American Academy of Dermatology Association. Actinic keratosis: who gets and causes. N.D. Available from [LINK]
  18. Fuchs and Marmur. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. 2007. Available from [LINK]
  19. Morice et al. Actinic keratosis of the scalp. License [CC BY 4.0]. Available from [LINK]
  20. Patient.info. Squamous cell carcinoma of the skin.2021 Available from [LINK]
  21. Unknown. Bowen disease. License [CC BY-SA 3.0]. Available from: [LINK]
  22. Valerie et al. Micrograph of invasive squamous cell carcinoma. License [CC BY 4.0]. Available from: [LINK]
  23. Keohane et al. British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020. 2020. Available from [LINK]
  24. NICE. Skin cancers- recognitions and referral. 2021. Available from [LINK]
  25. DermNet NZ. Cryotherapy. 1997. Available from [LINK]
  26. Cancer Research UK. Mohs micrographic surgery (MMS) for skin cancer. N.D. Available from [LINK]
  27. Patel and Chang. Immune Checkpoint Inhibitors for Treating Advanced Cutaneous Squamous Cell Carcinoma. 2019. Available from [LINK]
  28. skinhealthinfo.org. Squamous cell carcinomas. 2004. Available from [LINK]
  29. Dermnetnz. Risks and complications of skin surgery. 2012. Available from [LINK]

 

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