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Cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma ( cSCC ) is a malignant tumor of the keratinocytes originating within the epidermis or its appendages


Non melanoma skin cancer ( NMSC ) are a group of cancers made of
○ basal cell carcinoma ( BCC )
○ Bowen’s disease
○ cutaneous SCC ( cSCC )
○ early stage actinic keratosis cSCC is the second most common non-melanoma skin cancer after BCC & accounts for 10 % to
20 % of all skin malignancies It should also be kept in mind that cSCC grows faster than BCC and produces a Also note that several nations do not have SCC included in cancer registers and recent studies have cited a 1 : 1 ratio between SCC and BCC Incidence is rising possibly due to factors as
○ higher levels of sun exposure
○ increase in ageing population ( average onset mid 60’s )
○ increased sunbed use
○ improved detection / screening Highest incidence in Australia European studies have show a age standardized incidence from 9 to 96 / 100,000 males and 5 to 68 per 100,000 females Incidence increases with age , seen more often in men Cancer Research UK reports 151,739 new cases of non-melanoma skin cancers in 2015-17 In the USA more than a million cSCC cases are diagnosed / year


Risk factors – UV light – sun exposure- particularly in childhood and youth  , Male sex , increasing age , ionizing radiation exposure , chronically diseased or injured skin , Light skin ( Fitzpatrick types I to III ) that burns with ↑ UV exposure , blue or hazel eyes and red or blonde hair  Immunosuppression with solid organ transplant recipients – more often with heart and lung transplant than kidney as the patients tend to be older and have to take more intensive immunosuppressive regimen , Actinic keratosis -is most common precursor of cSCC , other conditions as bowenoid papulosis and epidermodysplasia verruciformis are also precancerous lesions with potential of transformation to cSCC , Human papilloma virus – particularly periungual and anogenital cSCC , Environmental exposure to arsenic , polycyclic aromatic hydrocarbons, nitrosamines and alkylating agents


What happens – cSCC originates from the epidermal keratinocytes from the suprabasal layer Several factors contribute to the carcinogenic process as
○ UV radiation which is able to generate specific mutations in DNA and reactive oxygen species
○ alterations in the regulation of p53 protein ( p53 protein stops cells with mutated or damaged DNA from replicating )
○ abnormalities in function of the RAS gene
○ oncogenic properties of the HPV
○ immunosuppression
○ physical and chemical carcinogens
○ chronic inflammatory and reparative disorders of the skin
○ tumor angiogenesis and its regulatory mechanisms
○ altered expressions of the receptor for epidermal growth factors SCC can arise from any skin surface including mucosa , the most common areas it affects are the sun exposed areas of of head , neck , arms and hands cSCC spreads by local infiltration and expansion and it may follow tissue planes and conduits as nerves and vessels.


Presentation – most common locations are face , neck , bald scalp , extensor forearms , dorsal hands and shins presents as scaly , erythematous papule with or without ulceration and haemorrhagic crust on chronically sun exposed skin of older patients colour can be flesh toned to erythematous with variable degrees of scale , crusting , ulceration on close inspection sometimes telangiectases with or without active bleeding may be noticed Hyperkeratosis may be quite pronounced and larger lesions may contain a central core of hard keratin and haemorrhagic debris they can be flat , nodular and even plaque like usually asymptomatic but they can occasionally be tender / bleed to touch ( tenderness can suggest perineural invasion ) differentiating from actinic keratosis can be difficult.


Actinic keratoses – seen mostly in whites , prevalence range from 11 % to 60 % above 40 considered as per-neoplastic lesions but some authors also suggest that they are carcinoma in situ neoplasms ( either way AC marks a patients increased risk of developing cSCC ) consist of intradermal proliferation of histologically atypical keratinocytes in areas of chronic sun damaged skin present as ,macules , papules or hyperkeratotic plaques with an erythematous background Cricione et al in 2009 reported that 65 % of cSCC arise from actinic keratosis – AC are thought to represent a continuum of progression from dysplastic keratinocytes to cSCC when they are multiple in a contiguous areas of skin with visible UV induced skin damage- it is called field cancerization the probability and speed at which AC may transition to cSCC can vary & is individual ,highly variable and unpredictable.


Basal cell carcinoma – epidermis has 5 sublayers and basal cells are found in the lower layer and here cells grow and divide to replace the outer cells SCC are found in the outermost layer of the epidermis usually differentiation is not difficult but SCCs are more likely to be misdiagnosed as BCC than vice versa ( features that suggest BCC are translucency , ulceration , telangiectasis , pigmentation and a rolled border ) dermoscopy can help but has limitations for some ambiguous lesions


Keratoacanthoma epithelial tumours which present as dome filled lesion with a central crater filled with keratin they grow rapidly for 4-6 weeks and regress spontaneously over the following 4-6 weeks ultimately leaving a slightly depressed annular scar distinguishing between the two can be challenging – particularly between KA and low grade SCC determining the nature of lesion is important as KA are benign lesions and they may be treated with excision biopsy whereas cSCC’s are malignant tumours with potential to metastasize and necessitates radical surgery


Verrucous carcinoma histopathological subype with low metastatic potential includes the Buschke-Lowenstein tumour found in genitalia and groin & epithelioma cuniculatum found on plantar surface of the foot


Bowen’s disease – epithelial limited SCC or SCC in situ -seen frequently in the elderly slowly progressive which may develop into SCC ( only in 3% to 5 % cases ) with a 20 % chance of metastatic dissemination typically located in areas exposed to sun as head , neck and legs presents as erythematous little scaly plaque which enlarges over time in an erratic manner the plaque can be yellow or white , easily detachable without producing any bleeding and reveals a wet , reddish surface well defined margins , affected skin is a bit raised and the surface is leveled but some times becomes hyperkeratotic or crusted.


NICE guidance – NICE guidance on SCC is fairly brief and simply states
 ” Consider a suspected cancer pathway referral for people with a skin lesion that raises the suspicion of squamous cell carcinoma


Dermoscopy can help in establishing the diagnosis , characterized by
○ small dotted vessels and glomerular vessels
○ pigmented cSCC can have small brown globules and gray brown homogenous pigmentation
○ invasive SCC can show looped / hairpin and serpentine vessels
Dermoscopy features of SCC can be difficult to visualise some times as the adherent surface scale often obscures the underlying morphological features
 Reflectance confocal microscopy – aims to bridge the gap between dermoscopy and histologic analysis – by permitting horizontal evaluation of a lesion ( as with dermoscopy ) while producing in vivo images of the epidermis and superficial dermis at a resolution that approximates that of a histopathologic specimens
 Skin biopsy is mandatory in all with suspected cSCC No evidence based optimal biopsy techniques exists for sampling potential cSCC -recommendations include
shave biopsy ,punch biopsy and excisional biopsy


Staging systems used can include
 American Joint Committee on Cancers ( AJCC ) 2016 Brigham and Women’s Hospital staging system.


Staging systems used can include
 American Joint Committee on Cancers ( AJCC ) 2016 Brigham and Women’s Hospital staging system.


Tumour diameter > 2.0 cm – doubles the risk of of SCC recurrence and triples the rate of metastasis
It is the risk factor most highly associated with disease -specific death and 19 fold higher risk of death compared to tumours < 2 cm ( Thompson et al )
 Tumour depth -tumours of Breslow thickness > 2 mm have a 10 fold higher risk of local recurrences and tumours extending beyond subcutaneous fat ( for e.g in deeper layers such as fascia , muscle , perichondrium and periosteum ) having a 10 fold higher risk of metastasis
 Perineural invasion – ie invasion of large caliber nerves or significant perineural involvement carrying a higher risk of local recurrences and metastatic risks
 Ear and lips SCC carry a much worse prognosis with risk of spread to regional lymph nodes and distant metastases
 Recurrent sSCC’s are twice as likely yo recur again after excisional surgery compared with primary tumours
 Other factors associated with local recurrence and metastasis include
◘ immunosuppression
◘ poor histologic differentiation
◘ age
◘ previous treatment.


Surgical excision is the primary mode of treatment for cSCC No biological / targeted therapy designed specifically yet for cSCC Moh’s micrographic surgery is the preferred excisional technique for SCC of head and neck and in other areas of high risk or SCC with high risk characteristic
○ also choice of treatment for SCC in the immunosuppressed , recurrence , large SCC’s ie > 2 cm
○ it provides higher cure rates with tissue conservation
○ here the surgeon is also the pathologist and performs real time comprehensive margin assessment of both peripheral and deep margins.


Complications – Metastases
◘ the most common site is the regional lymph nodes
◘ primary cutaneous SCC locate on the ear or lip are at the highest risk of metastasizing Local invasion Pain Loss of function Aesthetic outcome not satisfactory – most SCCs around the head & neck region require complex surgery Recurrence Death ( advanced SCCs carry a poor prognosis with a 5 yr survival rate of below 40 % )


5 page pdf from British Association of Dermatologists,can%20appear%20as%20an%20ulcer.

4 page PDF from Oxford University Hospitals .

American Academy of Dermatology Association on SCC

Christie’s page on SCC – a comprehensive resource

An educational page on SCC screening and diagnosis by Ohio State University



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