Skin Cancer — Types, Causes, Warning Signs & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Skin cancer is the most common cancer worldwide, arising from malignant transformation of skin cells — primarily caused by ultraviolet radiation exposure. The three principal types are: basal cell carcinoma (BCC), arising from basal keratinocytes of the epidermis; squamous cell carcinoma (SCC), arising from suprabasal keratinocytes; and melanoma, arising from melanocytes. BCCs and SCCs are collectively termed non-melanoma skin cancers (NMSC). Basal cell carcinoma is the most common cancer in humans — accounting for 75-80% of all skin cancers; it is locally invasive but rarely metastasises (below 0.1% of cases); however, if neglected, it can cause significant local tissue destruction including bone and cartilage erosion. Squamous cell carcinoma accounts for 15-20% and carries a higher metastatic risk — particularly for tumours arising in high-risk sites (ear, lip, non-sun-exposed skin), in immunosuppressed patients, or with perineural invasion (SCC metastasises in 2-5% of all cases but up to 30-50% in immunosuppressed transplant recipients). Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFSP), and cutaneous lymphomas are rarer non-melanoma skin cancers with distinct biology and management. In situ variants precede invasive cancer: actinic keratosis (AK) is a precursor to SCC (2-5% malignant transformation per AK/year); Bowen's disease is SCC in situ. The majority of skin cancers are curable when detected early — underlining the critical importance of skin awareness and sun protection.

Ultraviolet radiation is the primary cause of the majority of skin cancers. UVB radiation (290-320 nm) directly damages DNA, forming cyclobutane pyrimidine dimers and (6-4) photoproducts — causing the characteristic C→T and CC→TT transition mutations in tumour suppressor genes (TP53 — mutated in 50% of BCCs and 90% of SCCs). UVA radiation (320-400 nm) generates reactive oxygen species, causes indirect DNA damage, and is predominantly emitted by indoor tanning beds — which increase melanoma risk by 75% for use before age 35. Cumulative UV exposure is more strongly associated with BCC and SCC, while intermittent intense exposure (sunburn) correlates better with melanoma. Ionising radiation: prior radiotherapy to the skin area increases BCC and SCC risk at the irradiated site (latency 10-20 years). Human papillomavirus (HPV — subtypes 6, 11, 16, 18): certain HPV subtypes are associated with SCC of the genitalia, perianal region, and nail folds, particularly in immunosuppressed individuals. Immunosuppression: organ transplant recipients on calcineurin inhibitors (tacrolimus, ciclosporin) have 65-250-fold increased SCC risk and 10-fold BCC risk — SCC in transplant recipients is more aggressive. Genetic conditions: xeroderma pigmentosum (XP — impaired nucleotide excision repair causing extreme UV sensitivity and SCC/BCC/melanoma in childhood), Gorlin syndrome (PTCH1 mutation — multiple BCCs, medulloblastoma), and Muir-Torre syndrome (MSH2/MLH1 mutations — sebaceous carcinoma associated with Lynch syndrome internal malignancies). Arsenic exposure, coal tar, and chronic inflammatory skin conditions (lupus vulgaris, lupus erythematosus) are additional SCC risk factors.

Basal cell carcinoma (BCC) clinical presentations: nodular BCC — pearly, translucent, rolled edge papule or nodule on sun-exposed skin (face, ears, scalp); surface telangiectasia; may ulcerate centrally ('rodent ulcer'); superficial BCC — erythematous, scaly plaque with subtle rolled edge — occurs on trunk and limbs; morphoeic (sclerosing) BCC — waxy, scar-like, poorly defined margins — most locally aggressive subtype, frequently underestimated in size clinically. Squamous cell carcinoma (SCC) clinical presentations: indurated, erythematous, hyperkeratotic nodule or plaque on sun-exposed skin; may ulcerate and bleed; fast-growing compared to BCC; arising within areas of actinic keratosis or Bowen's disease (SCC in situ — well-demarcated, erythematous, scaly plaque); SCC of the lip arises on the vermilion border; SCC of the ear carries high metastatic risk. Actinic keratosis (AK — SCC precursor): rough, adherent, erythematous scaly patches on chronically sun-damaged skin — face, scalp, dorsum of hands; may be tender; sandpaper texture on palpation. Warning signs warranting urgent assessment for any skin lesion: rapid growth; ulceration or failure to heal; bleeding from a skin lesion; satellite nodules around a treated lesion; and firmness on palpation. Merkel cell carcinoma: violaceous, firm, rapidly growing dome-shaped nodule on sun-exposed skin of the elderly — aggressive behaviour, high metastatic rate.

Clinical assessment: dermatoscopy (dermoscopy) significantly improves clinical diagnostic accuracy — characteristic BCC dermoscopic features include arborising (tree-like) telangiectasia, leaf-like areas, blue-grey ovoid nests, and spoke-wheel structures; SCC shows irregular keratinisation, structureless areas, and hairpin vessels. Reflectance confocal microscopy (RCM) is an emerging non-invasive technique used at specialist centres. Biopsy: definitive diagnosis requires histological examination — choose biopsy technique based on suspicion: punch biopsy (diagnostic biopsy of a representative area); shave biopsy (for superficial lesions); incision biopsy (for large morphoeic or suspicious lesions where full excision is not immediately feasible); full elliptical excision biopsy (for definitive diagnosis and treatment of small, well-defined lesions with clear margin assessment). Histological reporting: tumour type and subtype, Breslow thickness (SCC and Merkel cell), perineural invasion, lymphovascular invasion, margin involvement, and tumour-infiltrating lymphocytes — reported by a specialist dermatopathologist. Staging investigations for high-risk SCC (perineural invasion, >4 mm depth, poorly differentiated, immunosuppressed host, ear or lip location): CT of regional lymph node basin, PET-CT for metastatic workup; sentinel lymph node biopsy for selected high-risk SCC (per NCCN guidelines). HPV testing for SCC in anogenital and oropharyngeal regions. Genetic testing (PTCH1, TP53, CDKN2A) for suspected hereditary syndromes (Gorlin syndrome, xeroderma pigmentosum). Multidisciplinary team (MDT) review at a skin cancer MDT for complex cases — all skin cancers above BCC should be discussed.

Surgical treatment: simple excision with histological margin assessment — standard for most BCCs and SCCs; margin recommendations: BCC 3-4 mm for well-defined nodular lesions, 5-6 mm for morphoeic BCCs; SCC 4-6 mm for low-risk lesions, wider for high-risk. Mohs micrographic surgery (MMS): the gold standard for high-risk BCCs (morphoeic, facial, large, recurrent, poorly defined margins) and high-risk SCCs — systematic, staged excision with immediate horizontal frozen section histological assessment of 100% of excision margins; achieves cure rates above 99% for primary BCC (vs 90-95% for standard excision); preserves maximum normal tissue — particularly valuable in cosmetically sensitive areas (nose, ears, eyelids, lips). Curettage and electrodesiccation (C&D): suitable for small, well-defined, superficial BCCs on non-critical sites; cure rates 85-90%. Cryotherapy (liquid nitrogen): superficial BCCs and actinic keratoses on non-critical sites. Radiotherapy: particularly for elderly patients unable to tolerate surgery, or for inoperable or recurrent lesions; effective for SCC and BCC; marginal for melanoma. Field treatment for multiple actinic keratoses: topical 5-fluorouracil (Efudix), diclofenac, imiquimod (Aldara — TLR7 agonist — immune response modifier), ingenol mebutate, photodynamic therapy (PDT — aminolaevulinic acid plus red light). Advanced and metastatic BCC: vismodegib (Erivedge) and sonidegib — Hedgehog pathway inhibitors (PTCH1/SMO mutations activate Hedgehog); response rates 48-60% but most relapse. Advanced/metastatic SCC: cemiplimab (Libtayo — anti-PD-1 immunotherapy) — 47% objective response rate (EMPOWER-CSCC-1 trial); pembrolizumab — also approved. Merkel cell carcinoma: avelumab (anti-PD-L1) and pembrolizumab — response rates 33-56% in Merkel cell carcinoma.

Local tissue destruction from untreated or recurrent BCC: neglected nodular BCCs erode progressively through dermis, subcutaneous tissue, fascia, muscle, cartilage, and bone — causing the 'rodent ulcer' appearance; periorbital BCCs can invade the orbit, requiring orbital exenteration; nasal BCCs may destroy nasal cartilage and bone, requiring major reconstructive surgery. Metastatic SCC: SCC of high-risk sites (ear, lip, non-sun-exposed skin, arising in chronic wounds or scars, or in immunosuppressed patients) metastasises to regional lymph nodes in 5-30%; untreated nodal metastases progress to distant organ spread. Transplant-associated skin cancer: SCC in organ transplant recipients is particularly aggressive — metastatic rate up to 30%, and can be rapidly fatal; cumulative SCC burden over decades is a major cause of morbidity and mortality in long-term transplant survivors. Treatment complications: Mohs surgery scarring, wound healing problems (particularly on lower leg in elderly patients), skin graft failure, radiotherapy-induced skin atrophy and telangiectasia, and increased secondary malignancy risk from field radiotherapy. Vismodegib side effects: muscle cramps (affecting 72%), alopecia (58%), dysgeusia (taste loss — 55%), and weight loss are dose-limiting in many patients. Psychological impact: facial disfigurement from large excisions and reconstructions causes significant body image disturbance and depression. Second primary cancers: patients with one NMSC have 10-fold increased risk of subsequent BCC and SCC — requiring lifelong skin surveillance.

Sun protection is the most effective primary prevention for all skin cancers. Apply broad-spectrum SPF 30-50 sunscreen 20 minutes before sun exposure and reapply every 2 hours and after swimming or sweating; sunscreen does not provide complete protection — physical UV barriers (clothing, hats) are essential. Wear UV-protective clothing (UPF 50+ fabric blocks >97% of UV radiation), wide-brimmed hat (minimum 7.5 cm brim shading face, neck, ears), and UV-400 sunglasses. Seek shade during peak UV hours (10am-4pm); check local UV index (above 3 requires sun protection). Avoid all indoor tanning — tanning beds emit concentrated UVA, significantly increasing skin cancer risk; IARC classifies them as Group 1 carcinogens. Actinic keratosis treatment: AK field treatment (topical 5-FU, PDT, imiquimod) in patients with multiple AKs reduces SCC risk by 70-80%; this is the most effective chemoprevention for SCC. Nicotinamide (vitamin B3) 500 mg twice daily: reduces new AK formation by 11% and new NMSCs by 23% in high-risk patients — safe, inexpensive, and recommended by NICE for patients with multiple AKs. Immunosuppression modification: where clinically feasible, converting to mTOR inhibitors (everolimus, sirolimus) from calcineurin inhibitors in transplant recipients reduces SCC incidence. Regular skin self-examination (monthly) and annual whole-body skin checks for high-risk individuals (fair skin, previous skin cancer, immunosuppression, occupational UV exposure) by a dermatologist.

See a GP promptly (within 2 weeks) for: any non-healing skin lesion that has been present for more than 4-6 weeks; any skin lesion that bleeds, ulcerates, crusts, or grows rapidly; a new or changing skin lesion on sun-exposed skin in a person over 40; and suspicious features on dermoscopy self-examination. Request an urgent 2-week-wait referral to a dermatologist for: a suspected BCC or SCC based on clinical features; any rapidly growing pigmented lesion with ABCDE features (asymmetry, irregular border, colour variation, diameter >6 mm, evolution); a suspected Merkel cell carcinoma (rapidly growing violaceous nodule); and any suspicious skin lesion in an immunosuppressed patient (organ transplant recipient, HIV, haematological malignancy) — these warrant same-week assessment given more aggressive behaviour. Go to A&E immediately for: a rapidly enlarging, bleeding, painful skin lesion that cannot wait; and any swelling, numbness, or motor weakness distal to a skin cancer lesion that might represent perineural invasion or vascular involvement. Transplant recipients should have 6-monthly whole-body skin checks by a dermatologist — they represent the highest risk group for rapidly progressive SCC.