Login:
 
Phillips C, Perkins W. Improving the detection of cutaneous squamous cell carcinoma. Practitioner June 2021;265(1849):23-26

Improving the detection of cutaneous squamous cell carcinoma

25 Jun 2021

AUTHORS

Dr Chris Phillips BMBS BMed Sci MRCP MRCGP, Dermatology Registrar

Dr William Perkins MBBS FRCP, Consultant Dermatologist, Churchill Hospital, Oxford, UK

Competing interests: None

Article

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer after basal cell carcinoma, with an estimated incidence of 77 per 100,000 patient-years. cSCC can develop de novo or from pre-existing chronic actinic damage, although the probability and speed of transition from actinic keratosis to cSCC is highly variable. The occurrence of cSCC is related to chronic UV exposure, particularly occupational exposure. Risk factors include fairer skin, significant exposure to sunlight or PUVA. Incidence is also significantly increased in patients who are immunosuppressed. cSCC usually presents as an enlarging, indurated, scaly, keratotic or crusted lump over a course of weeks to months. The lesions can be domed, crateriform or peaked in shape. They may ulcerate and can often be tender or painful. Common sites are sun exposed areas such as the scalp, temples, face, helical rim, lateral neck, forearms, hands and lower legs. They can range in size from a diameter of a few millimetres to several centimetres. Any evidence of surrounding sun damage should be recorded and the lesion should be palpated to elicit tenderness and determine whether it is mobile or fixed to deeper tissues. The draining lymph nodes should be palpated and a full skin check for other lesions should be performed. All patients with suspected cSCC should be referred via the two-week wait pathway to dermatology.


Cutaneous Squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer after basal cell carcinoma.

Since the early 1990s, non-melanoma skin cancer incidence rates have increased by 166% in the UK.1 A cohort study2 carried out from 2013 to 2015 estimated the incidence of cSCC as 77 per 100,000 patient-years with a 5% rise per annum.3

The presence of abnormal keratinocytes confined to the epidermis is termed actinic keratosis if dysplasia is partial epidermal thickness. In Bowen’s disease, also known as cSCC in situ, the dysplasia is of full epidermal thickness. Once the dysplastic keratinocytes breach the epidermal basement membrane and invade into the dermis, it becomes cSCC. The lesions may be well, moderately or poorly differentiated, see figure 1. They have the potential to cause local invasion and can metastasise to lymph nodes or other organs.4

Mucosal SCC has a different aetiology, and different referral pathways and treatment regimens, and is outside the scope of this article.

Risk factors

The occurrence of cSCC is related to chronic UV exposure, particularly occupational exposure. Risk factors include fairer skin (Fitzpatrick skin types I-II), significant exposure to sunlight or therapeutic UV radiation (PUVA). Given the long latency between exposure and the development of cSCC, increased life expectancy may also be contributing to the rising incidence.

The incidence is also significantly increased in patients who are immunocompromised. Solid organ transplant recipients have a 65 to 250-fold increased risk.5,6 Long-term exposure to azathioprine,7 which is photocarcinogenic, is a significant risk factor as is immunosuppression caused by haematological disease, especially chronic lymphocytic leukaemia which confers an 8-10 fold increased risk.8 cSCC is also associated with oncogenic HPV9 as well as genetic disorders such as albinism where melanin protection is absent and xeroderma pigmentosum where DNA repair after UV damage is impaired. Risk factors for cSCC are listed in table 1.

As well as developing de novo, cSCC can also develop from pre-existing chronic actinic damage10 although the probability and speed of transition from actinic keratosis to cSCC is highly variable.

Progression rates range from 0 to 0·075% per lesion-year. Rates of regression of actinic keratoses range between 15 and 63% after one year. After regression, the rate of recurrence is 15-53%.11 As such giving an accurate risk of an actinic keratosis transforming into cSCC to an individual patient is not straightforward.

The discussion needs to be put into the context of the prevalence rates for non-melanoma skin cancer within the patient’s age group, which for patients aged 65 years and over is 2%.

All patients should be given information on the signs to look out for, along with education on the importance of avoiding excessive sun exposure, the use of protective clothing and sun screens (SPF 30+).

Assessment

When taking the history it is important to check the patient’s risk factors and to consider the following:

• Whether there was a pre-existing burn, area of inflammation or area of Bowen’s disease or actinic keratosis

• How long the lesion has been present and how quickly it has grown

• Any history of pain or tenderness

• Whether the patient is on anticoagulants or has a clotting disorder. (This information will be particularly relevant to the operating surgeon)

When examining the patient it is important to record:

• The skin type

• Any evidence of surrounding sun damage (actinic keratoses, Bowen’s disease, tan)

• The location and diameter of the lesion

The lesion should be palpated to elicit tenderness, and to determine whether

it is mobile or fixed to deeper tissues. The draining lymph nodes should also be palpated.

A full skin check for other lesions should also be performed.

All patients with suspected cSCC should be referred via the two-week wait suspected cancer referral pathway to a dermatology department.12

Clinical presentation and diagnosis

cSCC usually presents as an enlarging, indurated, scaly, keratotic or crusted lump over a course of weeks to months. The lesions can be dome, crateriform or peaked in shape. They may ulcerate and can often be tender or painful. Common sites are sun exposed areas such as the  temple (see figure 2), scalp (see figure 3), face, helical rim, lateral neck, forearms (see figure 4), hands and lower legs. cSCC can also occur in burn scars (see figure 5). Lesions can range in size from a diameter of a few millimetres to several centimetres.

The less aggressive well differentiated lesions grow more slowly and usually have a nodular and exophytic growth with a keratotic surface from early on. The more aggressive, poorly differentiated lesions have less or no keratin. They may be more endophytic in growth and present with an ulcer with no nodular element at all.

Dermoscopy

Many features seen on dermoscopy are not specific to cSCC and as such dermoscopy must be used carefully in conjunction with the clinical history and examination with the naked eye. It is important to avoid blanching the blood vessels by pressing too firmly with the dermatoscope. For more nodular lesions, it is advisable to use a more viscous contact medium than alcohol gel such as ultrasound gel for better views.

Features which may be seen on dermoscopy include:

• Vessels:

— Hairpin with a white halo

— Glomerular

— Arborising

— Polymorphous

• White circles (intrafollicular keratin plugs)

• White structureless areas (cystic cavities of keratin)

• Poorly differentiated, ulcerating cSCCs have very non-specific signs and are predominantly a homogeneous red colour from dense vascularity and bleeding.

The differential diagnosis includes basal cell carcinoma, hypertrophic actinic keratosis and keratoacanthoma. A keratoacanthoma is a well differentiated self-healing cSCC and as it is not possible to differentiate a keratoacanthoma from cSCC clinically with confidence, all lesions should be referred for excision. The differential diagnosis for poorly differentiated cSCC also includes Merkel cell carcinoma and nodular melanoma.

A definitive diagnosis is made histologically following excisional or incisional biopsy. Once diagnosis is made the tumour is then staged using staging criteria such as the Union for International Cancer Control 8th edition (UICC8) criteria to give a tumour node metastasis (TNM) classification. This will determine prognosis and guide subsequent treatment options.

Treatment

There is no role for cryotherapy or topical treatments in the management of cSCC.

 

Surgery

The surgical treatment options are as follows:

Surgical excision: The vast majority of cSCC are treated by surgical excision. This is carried out with a surgical margin of 4-10 mm depending on the size of the tumour.

Mohs micrographic surgery: This approach is advisable if the lesion is in an area where tissue preservation is important such as near the eyelid margin.

Shave curettage and electrocautery: The option of shave curettage and electrocautery should only be considered for low risk, < 1 cm, thin cSCC such as those on the trunk or limbs in immunocompetent patients or for use in palliation.

 

Radiotherapy

Primary radiotherapy can be considered if the patient declines surgery or for palliation. Radiotherapy is more frequently used as an adjunct following surgery in higher risk cases.

Complications

Untreated, cSCC can cause local tissue destruction and metastasise to lymph nodes or other organs. cSCC usually spreads to local lymph nodes and clinically enlarged nodes should be examined histologically by fine needle aspiration or excision biopsy. Tumour-positive lymph nodes are then managed by regional lymphadenectomy whereby lymph nodes that drain the site of the tumour are removed with therapeutic intent. Imaging is performed to define the extent of regional disease and to identify distant metastases. Adjuvant radiotherapy or chemotherapy can also be considered. With respect to prognosis, several large studies have estimated a mortality rate for metastatic cSCC of more than 70%.14

Risk status

The risk of metastasis of cSCC is 1.1-2.6%.15,16,17 Which lesions are at particular risk of recurrence and metastasis to lymph nodes can be determined by the presence of factors which relate to the tumour itself (size, depth, histology) as well as the host (immune status), see table 2.

Follow-up

The duration and frequency of follow-up varies according to the risk status.

A patient classified as low risk has a 40% further chance of cSCC within the next five years. For high and very high risk patients, this risk increases to 80%.18

Follow-up will require a full skin check, palpation of draining lymph nodes and patient education on skin surveillance. Follow-up frequency is recommended as follows:18

 

Low risk cSCC

• Single post treatment appointment

 

High risk cSCC

Year 1: Every 4 months

Year 2: Every 6 months

 

Very high risk cSCC

Year 1 and 2: Every 4 months

Year 3: Every 6 months

 

Follow-up can be organised as a shared care arrangement with appointments alternating between the GP and secondary care. Encouraging patients to carry out self-examination and use sun protection strategies is vitally important.

Conclusion

The incidence of cSCC is increasing. Educating all patients, particularly those with risk factors, on skin self-examination and sun protection should be a routine part of GP consultations that relate to the skin. Early recognition of a suspicious lesion by the patient and subsequently the clinician will lead to earlier treatment which is associated with better outcomes for the patient.

REFERENCES

1 Cancer Research UK. Non-melanoma skin cancer statistics

2 Venables ZC, Nijsten T, Wong KF et al. Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013-15: a cohort study. Br J Dermatol 2019;181(3):474-82

3 Ciążyńska M, Kamińska-Winciorek G, Lange D et al. The incidence and clinical analysis of non-melanoma skin cancer. Sci Rep 2021;11:4337

4 Kwa RE, Campana K, Moy RL. Biology of cutaneous squamous cell carcinoma. J Am Acad Dermatol 1992;26(1):1-26

5 Jensen P, Hansen S, Møller B et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999;40(2 Pt 1):177-86

6 Hartevelt MM, Bavinck JN, Kootte AM et al. Incidence of skin cancer after renal transplantation in The Netherlands. Transplantation 1990;49(3):506-09

7 van den Reek JM, van Lümig PP, Janssen M et al. Increased incidence of squamous cell carcinoma of the skin after long-term treatment with azathioprine in patients with auto-immune inflammatory rheumatic diseases. J Eur Acad Dermatol Venereol 2014;28(1):27-33

8 Velez NF, Karia PS, Vartanov AR et al. Association of advanced leukemic stage and skin cancer tumor stage with poor skin cancer outcomes in patients with chronic lymphocytic leukemia. JAMA Dermatol 2014;150(3):280-87

9 Tommasino M. HPV and skin carcinogenesis. Papillomavirus Res 2019;7:129-131

10 Gutzmer R, Wiegand S, Kölbl O et al. Actinic keratosis and cutaneous squamous cell carcinoma. Dtsch Arztebl Int 2019;116(37):616-26

11 Werner RN, Sammain A, Erdmann R et al. The natural history of actinic keratosis: a systematic review. Br J Dermatol 2013;169(3):502-18

12 National Institute for Health and Care Excellence. NG12. Suspected cancer: recognition and referral. NICE. London. 2015 Updated 2021 www.nice.org.uk/guidance/ng12

13 Torchia D, Massi D, Caproni M et al. Multiple cutaneous precanceroses and carcinomas from combined iatrogenic/professional exposure to arsenic. Int J Dermatol 2008;47(6):592-93

14 Burton KA, Ashack KA, Khachemoune A. Cutaneous squamous cell carcinoma: a review of high-risk and metastatic disease. Am J Clin Dermatol 2016;17(5):491-508

15 Brougham ND, Dennett ER, Cameron R, Tan ST. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol 2012;106(7):811-15

16 Knuutila JS, Riihilä P, Kurki S et al. Risk factors and prognosis for metastatic cutaneous squamous cell carcinoma: a cohort study. Acta Derm Venereol 2020;100(16):adv00266

17 Venables ZC, Autier P, Nijsten T et al. Nationwide incidence of metastatic cutaneous squamous cell carcinoma in England. JAMA Dermatol 2019;155(3):298-306

18 Keohane SG, Botting J, Budny PG et al. British Association of Dermatologists’ Clinical Standards Unit. British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020. Br J Dermatol 2021;184(3):401-14