SCC Flashcards
What is SCC?
Primary cutaneous squamous cell carcinoma (SCC) is a malignant tumour that arises from the keratinising cells of the epidermis or its appendages.
It is locally invasive and has the potential to metastasise to other organs of the body
SCC is the second most common skin cancer behind BCC.
Pathophysiology of SCC
Malignant transformation of normal epidermal keratinocytes is the hallmark of SCC. The development of apoptotic resistance occurs through the functional loss of a tumour suppressor gene, TP53.
Ultraviolet radiation causes DNA damage through the creation of pyrimidine dimers, resulting in the genetic mutation of TP53. Upon subsequent UV exposure, keratinocytes undergo clonal expansion, acquiring further genetic defects, ultimately leading to invasive SCC.
Mutations of BCL2 and RAS genes are believed to contribute to the pathogenesis of SCC. Alterations in intracellular signal transduction pathways, including the epidermal growth factor receptor (EGFR) and cyclo-oxygenase (COX), have also been shown to play a role in the development of SCC.
Risk factors for SCC
Chronic UVR exposure is the most important risk factor.
UV light (therefore there is increased risk with holidays in the sun, outdoor occupations and leisure pursuits, and using tanning beds).
Susceptibility to UV light exposure: fair skin (skin that tans poorly), blonde or red hair.
Chemical carcinogens: arsenic and chromium, soot (scrotal cancers in chimney sweeps), tar and pitch oils.
Human papillomavirus infection.
Ionising radiation exposure.
Immunodeficiency.
Chronic inflammation: near chronic ulcers, around chronic sinuses (eg, osteomyelitis), lupus vulgaris (chronic form of cutaneous tuberculosis).
Genetic conditions – e.g., xeroderma pigmentosum and albinism.
Pre-malignant conditions – e.g., Bowen’s disease, areas of skin showing actinic damage.
Multiple actinic keratoses are associated with an estimated 10% lifetime risk of skin cancer.
keratoacanthomas may rarely progress to SCC.
An association with smoking
What is xeroderma pigmentosum?
Xeroderma Pigmentosum is an autosomal recessive condition resulting from a defect in DNA repair. This results in extreme sun sensitivity and a predilection for skin cancer.
Presentation of SCC
SCC usually presents as an indurated nodular keratinising or crusted tumour that may ulcerate, or it may present as an ulcer without evidence of keratinisation.
Typically, SCC presents as a non-healing ulcer or growth in one of the higher-risk sun-exposed areas. Most SCCs appear on the skin of the head and neck.
The clinical appearance is very variable:
• A small nodule enlarges and the centre becomes necrotic and sloughs, developing into an ulcer. The tumour therefore usually presents as an ulcerated lesion with hard, raised edges.
• Slow-growing ulcer or reddish skin plaque.
• Bleeding may occur from the tumour.
• SCC may give rise to local metastases or spread to local lymph nodes.
Differentials for SCC
Keratoacanthoma
BCC
Malignant melanoma particularly amelanotic malignant melanomas.
Actinic keratosis
Pyogenic granuloma
Seborrhoeic warts
Plantar warts
Investigations for SCC
Investigation is primarily by visual inspection and removal for histology where necessary.
Skin biopsy such as excisional biopsy or punch biopsy.
Imaging including CT and MRI to check for metastases.
Clinically enlarged nodes should be examined histologically.
Staging
Referral for SCC
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for people with a skin lesion that raises the suspicion of squamous cell carcinoma.
A photochemotherapy, rapid tumour growth, poorly defined clinical margins or pain/dysaesthesia
Management of SCC
There should be two levels of multidisciplinary teams: local hospital skin cancer multidisciplinary teams (LSMDTs) and specialist skin cancer multidisciplinary teams (SSMDTs).
The standard effective treatment is complete surgical excision and all excised specimens should be sent for histopathological examination.
Where the other non-surgical treatments exclude histological confirmation of the diagnosis, an incisional biopsy for confirmation of the diagnosis should usually be obtained before treatment
Other surgical and non-surgical procedures include:
Curettage and cautery- treat small in situ SCCs and pre-cancerous lesions.
Cryotherapy- small in situ SCCs and pre-cancerous lesions.
Topical treatment such as imiquimod 5% cream, fluorouracil and diclofenac gel.
PDT for in situ SCCs and actinic keratosis.
Electrochemotherapy:
Moh’s micrographic stage:
Is a precise technique in which excision of the skin lesion is carried out in stages and each stage checked histologically.
It is advocated for use in cases where it is critical to obtain a clear margin while preserving the maximum amount of normal surrounding tissue.
This procedure is more often used in the treatment of BCCs.
Radiotherapy
What is electro chemotherapy?
Chemotherapy drugs are given first, either intravenously or directly into the tumour.
Shortly after drug administration, brief and intense electric pulses are delivered around or directly into the tumour using either surface plates or needle electrodes.
What are the factors affecting the metastatic potential of SCC
Site: tumour location in order of increasing metastatic potential:
o SCC arising at sun-exposed sites excluding the lip and ear.
o SCC of the lip.
o SCC of the ear.
o Tumours arising in non-sun-exposed sites (eg, the perineum, sacrum, sole of foot).
o SCC arising in areas of radiation or thermal injury, chronic draining sinuses, chronic ulcers, chronic inflammation or Bowen’s disease.
Diameter: tumours greater than 2 cm in diameter are twice as likely to recur locally and three times as likely to metastasise.
Depth: tumours greater than 4 mm in depth (excluding surface layers of keratin) or extending down to the subcutaneous tissue (Clark level V) are more likely to recur and metastasise compared with thinner tumours.
Histological differentiation: poorly differentiated tumours have a poorer prognosis, with more than double the local recurrence rate and triple the metastatic rate of better-differentiated SCC.
Tumours with perineural involvement are more likely to recur and to metastasise.
Host immunosuppression: tumours arising in patients who are immunosuppressed have a poorer prognosis.
What is Bowen’s disease?
Bowen’s disease is a form of intraepidermal (in situ) squamous cell carcinoma (SCC) of the skin.
Bowen’s disease arises in the outer layers of the epidermis and the risk of progression to invasive SCC is relatively low at about 3% for typical cases.
Risk factors for Bowen’s disease
Sun damage: exposure to sunlight (especially with fair skin) is a strong risk factor.
Other irradiation damage: radiotherapy, photochemotherapy, sunbeds.
Carcinogens: particularly arsenic. Exposure to inorganic arsenic is less common than in the past. Arsenic used to be found in Fowler’s solution (used to treat psoriasis) and in Gay’s solution (used to treat asthma).
Viral infection: there is a strong association with human papillomavirus (HPV), particularly in genital and perianal lesions and in lesions on the hands and feet. (Often HPV-16 but several other HPV types have been implicated.)
Immunosuppression: therapeutic following organ transplants, or due to AIDS. Malignant and premalignant skin tumours are more common in patients who have received organ transplants. The risk may depend on the immunosuppressive regime used.
Chronic skin injury or dermatoses: rarely, it arises in pre-existing skin lesions such as seborrhoeic warts.
Presentation of Bowen’s disease?
It presents as a slowly growing erythematous, hyperkeratotic patch or plaque with an irregular border. It is sharply demarcated, scaling with a pink or red surface.
There may be a small erosion or it may be crusted. It may reach a few centimetres in size.
The size of a lesion is directly related to its duration.
Lesions are usually asymptomatic but can bleed.
Lesions are usually solitary but in 10-20% of cases there are multiple lesions.
They are most commonly found in sun-exposed areas: on the lower limbs in the UK (60-85%) or head and neck in Australia (44%), Denmark (40-59%) and the USA (66%). It is not known why there is a variation in the body site affected across different countries.
Other locations are subungual, periungual, palmar, genital or perianal. When it arises on the mucosal surfaces of the glans penis, it is referred to as erythroplasia of Queyrat (EQ). Some vulval lesions also have features of Bowen’s disease.
Differentials for Bowen’s disease
Discoid eczema Psoriasis Lichen planus Actinic (solar) keratosis Superficial BCC Malignant melanoma Paget’s disease of breast
