Cutaneous squamous-cell and basal-cell carcinoma

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Keratinocyte cancers are the commonest human malignancies. BCC is driven largely by hedgehog signalling and grows locally, sometimes extensively around nose, eyelid and ear, but metastatic spread is exceptional. cSCC evolves from UV-damaged field epithelium and has real nodal potential. A lesion’s diameter, depth, differentiation, site, immune context and neural involvement matter more than the simple label skin cancer.

Dermoscopy helps distinguish pearly arborising BCC from keratinising cSCC and pigmented mimics, but histology determines treatment. A punch may be adequate for a large lesion when it samples the deepest and most aggressive area; small lesions can be excised diagnostically. Pathology reports subtype, depth, differentiation, margins, perineural and lymphovascular invasion. Superficial sampling can miss infiltrative depth and must be repeated when palpation and histology disagree.

Standard excision is the default for most invasive tumours. Mohs removes mapped horizontal layers until the complete margin is clear, maximising tissue preservation at a high-risk face, recurrent border or aggressive subtype. Radiotherapy is an alternative or adjuvant for selected patients, margins and perineural risk. Topical and destructive therapies are appropriate only when diagnosis, superficial depth and low-risk site are secure.

Advanced care differs by lineage. Regional cSCC is treated with nodal surgery and radiotherapy in a site-specific MDT. Cemiplimab or another funded PD-1 inhibitor can control unresectable cSCC. BCC with unresectable local invasion may respond to smoothened inhibition or PD-1 treatment in a defined sequence. Transplant patients require a balance between cancer immune control and graft preservation, with prevention and repeated treatment integrated longitudinally.

Key points

BCC typically appears as a pearly telangiectatic papule, rolled-edge ulcer or scar-like plaque and is locally destructive but almost never metastasises.
cSCC commonly appears as a tender indurated keratotic or ulcerated lesion that grows over weeks or months and can spread to regional nodes.
First-line assessment includes full-skin and regional-node examination with dermoscopy and measurement; photograph site and size before biopsy.
The diagnostic reference standard is representative full-thickness biopsy or excision that permits invasive depth, differentiation, subtype and perineural and lymphovascular assessment.
High-risk cSCC features include ear or lip site, large diameter, depth beyond subcutaneous fat or over 6 mm, poor differentiation, perineural invasion, recurrence and immune suppression.
First-line treatment for most invasive BCC and cSCC is complete surgical excision with a clinically appropriate margin and pathological confirmation.
Mohs micrographic surgery is preferred for selected high-risk, recurrent, poorly defined or tissue-critical facial tumours because it examines the complete peripheral and deep margin while conserving tissue.
Curettage, cryotherapy, photodynamic therapy, topical imiquimod or fluorouracil are reserved for carefully selected superficial low-risk lesions and must not be used for suspected invasive high-risk cSCC.
A high-risk cSCC requires nodal examination at every review and ultrasound with FNA or core of a suspicious node; routine sentinel-node biopsy remains selective rather than standard for all.
Named-nerve symptoms require contrast MRI for perineural spread and combined surgical and radiation planning.
Locally advanced cSCC not suitable for curative surgery or radiotherapy may receive PD-1 blockade such as cemiplimab; advanced BCC can receive hedgehog-pathway treatment.
Transplant recipients need expedited treatment, regular field surveillance and transplant-team review of immune suppression rather than uncoordinated drug reduction.
Prevention combines shade, clothing, sunscreen, avoidance of tanning devices and surveillance without promoting complete sun avoidance or vitamin-D deficiency.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Ultraviolet radiation

Cumulative UV drives cSCC and intermittent and cumulative exposure contribute to BCC through DNA damage on sun-exposed skin.

Immune suppression

Solid-organ transplantation, haematological malignancy and immune-modifying drugs markedly increase cSCC incidence, multiplicity, recurrence and metastatic risk.

Chronic injury and carcinogen exposure

Radiation scars, burns, chronic ulcers, arsenic, tar and some HPV-related anogenital or periungual disease create additional cSCC pathways.

Inherited susceptibility

Gorlin syndrome causes multiple hedgehog-driven BCCs, while xeroderma pigmentosum and other DNA-repair disorders cause early numerous keratinocyte cancers.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
BCC activates hedgehog signalling
PTCH1 loss or related changes release smoothened-pathway activity in basal keratinocytes, producing slow local invasion with exceptionally rare distant metastasis.
2
cSCC follows field cancerisation
UV-induced TP53 and other mutations accumulate across clinically sun-damaged epidermis, producing actinic keratoses, in-situ SCC and independent invasive clones.
3
Dermal invasion creates metastatic access
Once cSCC crosses the basement membrane, increasing thickness, poor differentiation, lymphovascular and perineural invasion raise regional nodal risk.
4
Growth pattern determines margin behaviour
Nodular tumours form more circumscribed nests, while infiltrative, micronodular and morpheaform BCC and desmoplastic cSCC send clinically occult strands.
5
Immune surveillance restrains SCC
Loss of T-cell control after transplantation permits mutated keratinocyte clones to proliferate and metastasise more readily, supporting immune-based advanced treatment.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Nodular BCC

A translucent pearly papule with arborising vessels, rolled edge and central ulceration on sun-exposed face is classic.

Infiltrative BCC

A pale scar-like, ill-defined indurated plaque may extend beyond visible margins and requires margin-controlled treatment.

Invasive cSCC

A rapidly enlarging tender hyperkeratotic nodule or indurated ulcer, especially on ear, lip or scar, suggests invasion.

Perineural diseaseRed flag

New pain, tingling, numbness, facial weakness or formication along a nerve is a high-risk neurological sign.

Regional metastasis

A hard parotid, cervical, axillary or inguinal node draining an invasive cSCC requires ultrasound, tissue and cross-sectional staging.

Transplant-associated field disease

Numerous rapidly recurring keratotic lesions in an immunosuppressed patient indicate high cumulative and metastatic risk requiring coordinated surveillance.

Red flags requiring action

A rapidly enlarging tender keratotic nodule, indurated ulcer or non-healing lesion, especially on ear or lip, requires urgent SCC assessment.
Facial numbness, pain, weakness, formication or motor deficit suggests perineural spread and requires urgent MRI and specialist treatment.
A recurrent, poorly defined, morpheaform or infiltrative lesion on nose, eyelid, ear or lip needs margin-controlled surgical planning.
A hard parotid, cervical or other regional node in a patient with cSCC can be metastatic and requires imaging and tissue.
Transplant recipients and other immunosuppressed patients can develop multiple aggressive cSCCs with faster nodal spread.
Bleeding, deep fixation, bone exposure, orbital symptoms or a chronic ulcer arising in scar or radiation field suggests advanced high-risk disease.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line dermoscopy and complete examinationFirst stepFirst line
Why
Assess lesion pattern, margin, size, fixation and field damage and examine regional nodes and the remaining skin.
Interpretation and limitations
Record exact anatomical landmarks and photograph with consent; tenderness, induration and neural symptoms can signal deeper risk beyond the surface image.
02
Reference full-thickness biopsy
Why
Confirm lineage and measure invasive depth, differentiation and aggressive growth pattern before definitive treatment.
Interpretation and limitations
Choose excision for a small removable lesion or a deep incisional or punch sample from the thickest edge; repeat superficial discordant tissue.
03
Definitive excision pathologyDefinitive
Why
Report margins, diameter, depth, subcutaneous invasion, differentiation, perineural and lymphovascular invasion and BCC subtype.
Interpretation and limitations
A close or positive margin is interpreted with tumour risk and anatomy; infiltrative strands and named-nerve involvement favour re-excision, Mohs or adjuvant radiation.
04
Ultrasound-guided node sampling
Why
Confirm regional cSCC metastasis in a suspicious parotid, cervical, axillary or inguinal basin.
Interpretation and limitations
Use FNA or core and map the primary drainage; a negative sample may need repeat or excision if imaging and clinical probability remain high.
05
MRI for perineural spread
Why
Define named-nerve, skull-base, foraminal, orbital and intracranial extension when neurological symptoms or pathology raises concern.
Interpretation and limitations
Use contrast and a dedicated nerve pathway protocol; microscopic perineural invasion may be below resolution but still influences adjuvant treatment.
06
CT or PET-CT for advanced cSCC
Why
Assess nodal, lung, bone and other distant disease and local bone or organ invasion before radical treatment.
Interpretation and limitations
Use in high-risk, node-positive or symptomatic disease rather than every low-risk lesion and biopsy an unexpected management-changing focus when feasible.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Actinic keratosis and SCC in situ

Rough field lesions and Bowen disease remain epidermal, but tenderness, thickness, rapid growth, ulceration or induration raises invasion and requires biopsy.

Keratoacanthoma

A rapidly growing crateriform nodule may involute but cannot be reliably distinguished from well-differentiated cSCC clinically and is generally excised.

Melanoma

Pigmented BCC and amelanotic or desmoplastic melanoma can mimic keratinocyte cancer; dermoscopy and immunohistochemical pathology determine lineage.

Benign inflammatory lesion

Eczema, psoriasis, wart, cyst and chronic infection can scale or ulcerate, but non-healing induration or repeated bleeding needs tissue.

Adnexal and Merkel-cell carcinoma

Rare sweat-gland, follicular and neuroendocrine tumours may resemble BCC or cSCC but carry different nodal and systemic treatment requirements.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Suspicious lesionBiopsy deep enough to classify riskFirst stepA non-healing, enlarging, ulcerated, keratotic, pearly or scar-like lesion is clinically suspicious.

1Assess growth, pain, immune suppression, previous cancer and neural symptoms and perform dermoscopic full-skin and nodal examination with measurement and photograph.
2Obtain full-thickness excision or incisional biopsy from the most representative deep area, avoiding destructive treatment before invasive risk is known.
3Review pathology against the clinical border and refer high-risk site, subtype, depth, recurrence or immune context to the specialist skin-cancer MDT.

02Low-risk primaryExcise completely with verified marginsHistology confirms a small, well-defined low-risk BCC or cSCC at a non-critical site.

1Choose standard surgical excision with the tumour-specific clinical margin and orient the specimen for complete pathological assessment.
2Use a superficial topical or destructive option only for a lesion whose diagnosis, depth, site and patient follow-up make surgery unnecessary or disproportionate.
3Confirm clearance, provide wound and scar care and establish prevention and skin self-examination because another keratinocyte cancer is common.

03High-risk or facialUse margin control and multidisciplinary reconstructionTumour is recurrent, aggressive, poorly defined, neural, deeply invasive or lies on a tissue-critical facial site.

1DefinitiveMap local, nodal and perineural extent with biopsy, ultrasound and MRI or CT and discuss surgery, reconstruction and radiation before definitive excision.
2Use Mohs or another complete-margin assessment approach where it improves clearance and tissue conservation, and stage or treat draining nodes for high-risk cSCC.
3Add radiotherapy for selected perineural, nodal, margin or unresectable risk and monitor nerve function and nodal basins closely.

04Advanced diseaseConfirm unresectability before systemic therapycSCC or BCC cannot be cured safely by surgery or radiotherapy or has metastatic spread.

1Confirm histology and stage, review previous surgery and radiation, performance, transplant and autoimmune context and reconsider specialist resection or combined local treatment.
2Use PD-1 blockade for eligible advanced cSCC and a hedgehog inhibitor or current later-line option for advanced BCC within exact funding criteria.
3Assess response, immune or pathway toxicity and wound, pain, bleeding and infection early and integrate palliative and reconstructive support.

05Immune suppressionReduce future burden without risking the graftA transplant recipient or immunosuppressed patient develops recurrent or high-risk keratinocyte cancers.

1Treat each suspicious lesion promptly and shorten skin and nodal surveillance intervals according to tumour number and risk.
2Discuss immune-suppression modification and possible mTOR-based strategy with transplant specialists, never changing graft medication independently.
3Use field treatment, rigorous photoprotection and selected systemic chemoprevention through a specialist team while monitoring renal, lipid, liver and mucocutaneous effects.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides local immune treatment for selected small superficial BCC at low-risk sites when surgery is unsuitable or not preferred.

Imiquimod for superficial BCC

Apply imiquimod 5% cream thinly to the lesion and a small surrounding margin five nights each week for 6 weeks, washing off after approximately 8 hours, within the licensed superficial-BCC criteria.

Confirm subtype and exclude invasion first; expect erythema and erosion, pause for severe reaction and review clinically after healing because apparent inflammation is not proof of clearance.

Blocks PD-1 and can produce durable regression in immunogenic advanced cutaneous squamous cancer.

Cemiplimab for advanced cSCC

Give cemiplimab 350 mg intravenously every 3 weeks within the licensed and current NICE-funded indication for metastatic or locally advanced cSCC not suitable for curative surgery or radiation.

Assess transplant and autoimmune disease carefully and monitor for immune lung, bowel, liver, endocrine, kidney, heart, skin and neurological toxicity during and after treatment.

Inhibits smoothened in the hedgehog pathway that drives most BCC and can shrink otherwise destructive local disease.

Vismodegib for advanced BCC

Give vismodegib 150 mg orally once daily within the funded indication for symptomatic metastatic or locally advanced BCC unsuitable for surgery or radiotherapy.

It is highly teratogenic and needs stringent pregnancy prevention; monitor muscle spasm, dysgeusia, weight loss, alopecia and interactions and assess whether response enables local treatment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Local tissue destruction

BCC and cSCC can erode cartilage, bone, orbit, nose, ear and nerves, causing disfigurement, bleeding, pain and loss of function.

Perineural spread

High-risk cSCC and infiltrative BCC can track named nerves toward skull base, causing pain, sensory change, weakness and intracranial extension.

Regional and distant metastasis

cSCC can spread to parotid, cervical or other basin nodes and later lung or distant organs; ordinary BCC almost never metastasises.

Multiple and recurrent cancers

Field damage and immune suppression cause repeated independent primaries, while incomplete or inappropriate treatment increases local recurrence complexity.

Treatment morbidity

Excision, reconstruction and radiotherapy can alter eyelid, lip, ear, facial nerve and cosmesis, while immunotherapy can inflame any organ.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Confirm histological clearance and review healing, graft or flap perfusion, sensory and motor nerve function and cosmetic and functional outcome after surgery.
Use risk-based full-skin and nodal follow-up, with shorter intervals for transplant, multiple, recurrent, high-risk cSCC and genetic syndromes.
Teach monthly self-examination and prompt review of a growing, tender, bleeding, non-healing or neurologically symptomatic lesion or new node.
During field or topical treatment, assess adherence, inflammatory response and healing and biopsy persistent induration or ulceration rather than repeating courses blindly.
During PD-1 therapy, review every organ system and protocol blood tests during and after treatment; delayed immune toxicity remains possible.
During vismodegib, track weight, taste, muscle symptoms, contraception and quality of life and stop ineffective treatment rather than tolerating indefinite burden.
Coordinate transplant function, rejection risk and immune-suppression changes with the transplant team and monitor interactions and renal and metabolic effects.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

BCC risk is local rather than metastatic

Its danger lies in silent infiltration of nose, eyelid, cartilage, bone and nerves, not ordinary distant spread.

Tenderness favours invasive SCC

Pain or tenderness in a keratotic lesion correlates with deeper invasion or perineural irritation and should accelerate biopsy.

Visible border can underestimate tumour

Morpheaform BCC and desmoplastic cSCC send strands beyond surface change, making complete margin examination especially valuable.

The parotid is a nodal basin

Temple, ear and scalp cSCC can metastasise to intraparotid nodes before the neck, so parotid examination and imaging matter.

Topical inflammation is not clearance

A vigorous imiquimod reaction confirms immune activation but not histological eradication; the healed site still needs review.

Transplant decisions are shared

Reducing immune suppression may slow cancer but risks graft loss, requiring dermatology, oncology and transplant collaboration.

11Common pitfallsFrequent interpretation and management errors.

01
Calling all non-melanoma skin cancers harmless and missing high-risk cSCC.
02
Using superficial biopsy that cannot assess invasion despite a thick or indurated lesion.
03
Destroying a suspected invasive cSCC with cryotherapy or curettage before histology.
04
Using topical imiquimod for nodular, infiltrative or high-risk facial BCC without appropriate confirmation.
05
Ignoring ear, lip, depth, poor differentiation, perineural and immune-suppression risk.
06
Treating a recurrent nasal or eyelid tumour with repeated standard excisions instead of margin-controlled review.
07
Failing to examine parotid and regional nodes in high-risk head-and-neck cSCC.
08
Attributing facial pain or numbness to scar without MRI for perineural spread.
09
Changing transplant immune suppression without the transplant team.
10
Assuming local redness after topical treatment proves cure.