Cutaneous Squamous Cell Carcinoma (cSCC): Dysplasia to Invasion

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of skin cancer after basal cell carcinoma (BCC) (Najjar 2020).

While cSCC is a less serious form of skin cancer than melanoma, it can grow quickly and spread, causing potentially serious complications if untreated (CCV 2018; Mayo Clinic 2019).

However, If addressed early, cSCCs can be easily resolved in most cases (Skin Cancer Foundation 2020).

cSCC has several features distinguishing it from BCC and melanoma. Awareness of these differences can assist with timely referral and treatment, thereby reducing morbidity associated with aggressive tumours and enhancing overall patient outcomes. All healthcare professionals should be able to identify lesions and refer appropriately.

What is cSCC?

cSCC is triggered by DNA mutation (caused by UV radiation or other factors) to the flat cells located in the upper layer of the epidermis, known as squamous cells. This mutation causes the squamous cells to grow and divide abnormally. cSCCs grow quickly over weeks or months (CCV 2018; Skin Cancer Foundation 2020; Healthdirect 2018).

Squamous cells can be found in many parts of the body, all of which are susceptible to developing cSCC. However, in most cases, cSCCs appear on areas of skin that are most frequently exposed to UV radiation (Healthdirect 2018). These include:

• Face;
• Lips;
• Hands;
• Ears;
• Forearms; and
• Lower legs.

(Oakley 2015)

Bowen’s disease is a pre-cancerous form of cSCC that generally presents as a red, scaly patch. If unaddressed, it may develop into cSCC (Healthdirect 2018).

Note: While ‘cutaneous squamous cell carcinoma’ specifically refers to cancer of the skin, squamous cell cancers can also develop internally (e.g. in the mouth, throat or lungs). These are known as ‘squamous cell carcinoma (SCCs)’ (Skin Cancer Foundation 2020).

cSCC v BCC v Melanoma

(CCV 2018; American Cancer Society; 2019; SunSmart 2018)

Prevalence of cSCC

There are about 777 000 new cases of cSCC and BCC in Australia every year, with cSCC accounting for about 30% of this figure. cSCCs most commonly affect people over the age of 50 (CCV 2018).

cSCC and BCC combined cause about 560 deaths annually (CCA 2019).

Risk Factors for cSCC

• Being male;
• Being over the age of 50;
• Fair complexion (particularly if the individual has freckles, blonde or red hair or blue or green eyes);
• History of skin cancer (cSCC or another type);
• Precancerous growths (e.g. actinic keratosis, actinic cheilitis, leukoplakia, Bowen’s disease);
• Direct ultraviolet (UV) exposure (either from the sun or artificial sources);
• History of sunburns;
• Reduced immune function due to illness or immunosuppressive medications;
• Exposure to ionising radiation or chemical carcinogens;
• Human papillomavirus (HPV) infection;
• Individual response to chronic inflammation (such as a burn site); and
• Certain genetic disorders such as xeroderma pigmentosum.

(Skin Cancer Foundation 2020; Mayo Clinic 2019)

About 90% of cSCC cases can be attributed to UV exposure (Skin Cancer Foundation 2020).

Warning Signs of cSCC

There are a number of signs to look for when identifying potential cSCCs as they can present in a variety of ways. Surface changes may include:

• Thick, red, scaly patches that may bleed or crust;
• Raised growths or lumps, possibly with a depression in the middle;
• Raised areas or new sores on existing scar or ulcer sites;
• Open sores (possibly with oozing or crusting) that do not heal, or heal and then reappear;
• Wart-like growths;
• Flat sores with crusting;
• Cutaneous horn;
• Keratoacanthoma; and
• Carcinoma cuniculatum.

(Skin Cancer Foundation 2020; Mayo Clinic 2019)

The lesion will generally range between a few millimetres to several centimetres in diameter and might be inflamed or tender (Oakley 2015).

Dysplasia

Dysplasia is the abnormal growth of a pre-existing lesion, from which cSCCs can develop. Initially, dysplastic keratinocytes above the epidermal basal layer behave abnormally, resulting in a focally thickened stratum corneum (SC); i.e. an actinic keratoses (AK) (Ratushny et al. 2012).

If the atypical keratinocytes demonstrate advancing dysplasia and dysfunction that fully infiltrates the epidermis, this becomes cSCC in situ, Bowen’s disease or intraepidermal carcinoma. A specific histological definition can highlight the lesion’s level of abnormality (Ratushny et al. 2012).

Well-differentiated cSCC’s most closely resemble normal tissue and are more predictable in behaviour than moderately well or poorly differentiated cSCCs, which are the most unpredictable tumours with poorer outcomes (Ratushny et al. 2012).

These less dysplastic, well-differentiated lesions retain some normal tissue function and can produce keratin, which may appear initially as a cutaneous horn (spiky, hard and often painful to the touch) (Ratushny et al. 2012).

Diagnosis and Treatment of cSCC

A cSCC can be diagnosed through physical examination and biopsy if required (Mayo Clinic 2019).

The severity of the cSCC will dictate the appropriate treatment option. cSCCs and other cancers are often categorised using a staging system known as tumour-node-metastasis (TNM), which assesses three aspects of the cancer (EdCaN 2014):

1. (T) Primary tumour
   • Size of the tumour;
   • Whether any high-risk features are present (lesion is over a certain size, poor differentiation, growing around a nerve, on the lip or ear); and
   • Whether there is an invasion of facial or skeletal structures.
2. (N) Regional Lymph Nodes
   • Whether the cancer has spread to lymph nodes; and
   • If so, the location, size and number of metastatic tumours.
3. (M) Metastasis
   • Whether the cancer has spread to distant areas of the body.

(O’Brien 2017)

A comprehensive explanation of the TNM staging system can be found on the Cancer Council Australia website.

cSCC Treatment

Treatment of cSCCs aims to completely remove the tumour in order to avoid recurrent disease or metastasis.

Depending on the patient’s characteristics, low-risk tumours (e.g. well defined, well-differentiated, small, thin and well-sited) can be treated with destructive modalities like curettage, cautery or topical creams.

High-risk tumours require complete excision. Challenging sites, e.g. thick, invasive lesions and lymph node involvement require a referral for comprehensive management (Skin Cancer Foundation 2020).

Conclusion

While cSCCs are not usually difficult to treat if addressed early, they have the potential to cause complications if left alone. Therefore, nurses working in all healthcare settings should have up-to-date knowledge of tumour types so that they can promptly identify cSCCs and determine the appropriate treatment for the patient.

Additional Resources

• Cancer Council Australia, TNM Classification of Primary Cutaneous Carcinomas
• Cancer Council Victoria, Skin Cancer
• DermNet NZ, Cutaneous Squamous Cell Carcinoma (with images)
• Is Basal Cell Carcinoma on Your Radar?
• Melanoma Diagnosis Recommendations and Treatment Options

References

• American Cancer Society 2019, What Are Basal and Squamous Cell Skin Cancers?, American Cancer Society, viewed 31 July 2020, https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/about/what-is-basal-and-squamous-cell.html
• Cancer Council Australia 2019, Keratinocyte Cancer: Prognosis, CCA, viewed 31 July https://wiki.cancer.org.au/australia/Guidelines:Keratinocyte_carcinoma/Prognosis
• Cancer Council Victoria 2018, Skin Cancer, CCV, viewed 31 July 2020, https://www.cancervic.org.au/cancer-information/types-of-cancer/skin_cancers_non_melanoma/skin-cancer-overview.html
• EdCaN 2014, Cancer Grading and Staging, Cancer Australia, viewed 4 August 2020, http://edcan.org.au/edcan-learning-resources/supporting-resources/biology-of-cancer/cancer-signs-and-symptoms/grading-and-staging
• Healthdirect 2018, Squamous Cell Carcinoma, Healthdirect, viewed 31 July 2020, https://www.healthdirect.gov.au/squamous-cell-carcinoma
• Mayo Clinic 2019, Squamous Cell Carcinoma of the Skin, Mayo Clinic, viewed 31 July 2020, https://www.mayoclinic.org/diseases-conditions/squamous-cell-carcinoma/symptoms-causes/syc-20352480
• Najjar, T 2020, Cutaneous Squamous Cell Carcinoma, Medscape, viewed 31 July 2020, https://emedicine.medscape.com/article/1965430-overview#showall
• Oakley, A 2015, Cutaneous Squamous Cell Carcinoma, DermNet NZ, viewed 31 July 2020, https://dermnetnz.org/topics/cutaneous-squamous-cell-carcinoma/
• O’Brien, S 2017, Stages of Squamous Cell Carcinoma, SkinCancer.net, viewed 31 July 2020, https://skincancer.net/types-signs/squamous-cell-carcinoma-stages/
• Ratushny, V, Gober, MD, Hick, R, Ridky, TW & Seykora, JT 2012, ‘Keratinocyte to cancer: the pathogenesis and modelling of cutaneous squamous cell carcinoma’, The Journal of Clinical Investigation, vol. 122, no. 2, pp. 464–72, viewed 15 November 2015, http://doi.org/10.1172/JCI57415
• Skin Cancer Foundation 2020, Squamous Cell Carcinoma Overview, Skin Cancer Foundation, viewed 31 July 2020, https://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma/
• SunSmart 2018, Skin Cancer Types, SunSmart, viewed 31 July 2020, https://www.sunsmart.com.au/skin-cancer/skin-cancer-types#:~:text=There%20are%20three%20main%20types,squamous%20cell%20carcinoma%20and%20melanoma.