Nodular melanoma is responsible for a disproportionate share of melanoma deaths — it grows rapidly, primarily in a vertical (downward) direction rather than radially across the surface, and therefore quickly reaches the dermis and deeper structures, producing early haematogenous metastasis. The critical clinical challenge: nodular melanoma often lacks the classic ABCDE features (asymmetry, border irregularity, colour variation, diameter >6 mm, evolution) because it is small, uniformly dark or amelanotic, and has relatively regular borders in its early stages. The EFG rule (Elevated, Firm, Growing) was developed specifically for nodular melanoma — any elevated, firm, growing nodule should prompt consideration of a suspected cancer pathway referral (NICE: consider for a lesion suggesting nodular melanoma), without waiting for ABCDE features. Amelanotic melanoma (lacking melanin pigment) may appear as a pink, red, or flesh-coloured lesion and can be misdiagnosed as a granuloma, pyogenic granuloma, dermatofibroma, or angioma. Any growing pink nodule on sun-exposed skin in an older patient needs urgent specialist assessment.

Lentigo maligna deserves specific attention as a pigmented skin lesion that bridges benign and malignant categories — it is a form of in situ melanoma (melanoma confined to the epidermis) that appears as a large, slowly growing, irregularly pigmented flat patch on sun-damaged skin, typically the face of elderly patients. It may have been present for years before a GP notices it or the patient presents with concern. The difficulty: lentigo maligna (LM) can be extremely difficult to distinguish clinically from a benign solar lentigo (age spot) — both are flat, brown, occur on sun-exposed facial skin. The distinguishing features: LM is larger (typically >10-15 mm), more irregular in shape, has areas of darker pigmentation within a lighter background (satellite spots), and may have lighter areas within it (regression). When LM progresses to invasive melanoma (lentigo maligna melanoma, LMM), there is typically a darker nodular area arising within the flat patch. Any flat irregular pigmented facial lesion in a patient over 60 that has been present for years but is gradually expanding deserves dermatology suspected cancer pathway referral.

Dermoscopy training for GPs represents one of the highest return-on-investment clinical skills in primary care — the RCGP Dermoscopy Certificate course (online + practical) trains GPs to use a hand-held dermoscope to distinguish benign from potentially malignant pigmented lesions, which can improve diagnostic accuracy when used with appropriate training and competence. The NHS benefit: a trained GP dermoscopist can confidently reassure and discharge patients with clearly benign lesions (seborrhoeic keratosis, dermatofibromas, angiomas, common naevi) that would otherwise be referred on the suspected cancer pathway — reducing unnecessary dermatology waiting times. Conversely, trained dermoscopy identifies subtle melanoma features (irregular pigmented network, atypical vascular patterns, regression structures) in lesions that appear benign clinically. The RCGP has an accredited dermoscopy learning pathway. For GPs without dermoscopy, local teledermatology services may allow dermoscopic images to be reviewed remotely by a specialist. If a lesion is equivocal, refer rather than reassure.

The fluorouracil 5% cream (Efudix) counselling is critical for patient adherence and avoiding premature treatment cessation — 5-FU works by inhibiting thymidylate synthetase, preventing DNA synthesis in rapidly dividing cells (AK keratinocytes). The treatment course causes a predictable inflammatory reaction: the treated skin becomes progressively more red, then blistered and crusted (from approximately day 10-14), reaching maximum inflammation by day 21-28. This reaction is EXPECTED and is a sign that the treatment is working — it represents the immune-mediated destruction of premalignant cells. Patients who are not warned about this reaction will stop treatment prematurely because they believe they are having an adverse reaction. GPs prescribing Efudix must: (1) provide written information about the expected inflammatory process; (2) explain when to stop and seek review — severe pain, ulceration, infection or ocular exposure — and that any interruption should follow product guidance and clinical review; (3) advise sunscreen on treated areas; (4) advise not applying to eyelids/periorbital, intertriginous, mucous membrane or broken skin, and not to a lesion that may be invasive SCC; and (5) book a review after the course and healing phase, at the agent-specific interval, to assess treatment response and consider repeat courses.

The GP cryotherapy of solitary actinic keratosis is a primary care procedure that reduces unnecessary dermatology referrals — GPs trained in cryotherapy can treat solitary or small numbers of clinically clear AKs in the practice using liquid nitrogen. The technique: single lesion treatment with liquid nitrogen spray or cotton swab, freeze-thaw cycle of approximately 5-15 seconds depending on lesion thickness, producing a halo of 1-2 mm around the lesion. Repeat at 4-6 weeks if residual lesion. The clinical governance requirements: GP confidence in the diagnosis (typical rough scaly lesion on appropriate location — if any doubt, refer rather than treat), documentation of the lesion (description, location, photograph), and follow-up at 4-6 weeks to confirm healing. Contraindications to primary care cryotherapy: uncertain diagnosis, periorbital location (risk to eye), lesion on dark skin (post-inflammatory hypopigmentation), very thick or hyperkeratotic lesions (require curettage or surgical excision rather than cryotherapy).

The melanoma staging system (Breslow thickness) explains why primary care excision is contraindicated — melanoma staging is determined by the Breslow thickness (the depth of invasion of the melanoma from the granular layer of the epidermis, measured in mm on histology), the mitotic rate, and the presence or absence of ulceration. These measurements require: (1) usually complete excision of the entire lesion rather than partial biopsy (the specialist decides); (2) the specimen must be oriented and processed with margins intact; (3) margins planned by the specialist team, with any wider excision determined by histology. Non-specialist excision of a suspected melanoma may be insufficient for staging and may compromise further management. The correct primary care action: suspected cancer pathway referral, avoiding partial biopsy or non-specialist excision.

Mohs micrographic surgery is a specialist margin-controlled procedure for selected high-risk BCCs, not a GP treatment option — it is particularly useful for BCCs at anatomically critical sites (periorbital, nasal tip, lip, ear) where tissue conservation is aesthetically and functionally essential. The technique: serial horizontal excision of thin layers of tissue, with immediate frozen section histological examination of the entire excision margin at each layer — the surgeon removes only tissue where tumour is identified. It achieves high cure rates while minimising normal tissue sacrifice. It is performed under local anaesthesia as a day case. In UK primary care, the GP's role is to recognise BCC (if melanoma is suspected — suspected cancer pathway referral) and refer to the appropriate service. High-risk facial BCCs are referred to specialist care, which decides whether Mohs surgery is indicated.

The immunotherapy-related adverse events (irAEs) from checkpoint inhibitors used in advanced melanoma treatment are an increasingly important area for GP awareness — as pembrolizumab (anti-PD-1) and ipilimumab (anti-CTLA-4) become standard treatment for stage III-IV melanoma (and are used adjuvantly in resected stage III melanoma), GPs will encounter patients on these agents presenting with immune-related complications. The key irAEs by organ system: GI (colitis — diarrhoea, abdominal pain, bloody stool, fever → high-dose prednisolone 1-2 mg/kg/day + urgent oncology review); endocrine (thyroiditis — check TFTs in any patient on checkpoint inhibitor with fatigue or weight change; hypophysitis — headache + pituitary hormone deficiency; adrenalitis — Addison-like crisis); pulmonary (pneumonitis — new dyspnoea + bilateral infiltrates on CXR → urgent oncology); dermatological (severe rash, bullae, Stevens-Johnson syndrome → dermatology urgently). The key GP principle: any patient on immunotherapy presenting with a new organ-system symptom should have irAE considered and the oncology team contacted — early high-dose corticosteroid treatment prevents severe irAE.

The 'EFG rule' for nodular melanoma identification is a clinical tool that complements ABCDE and should be in every GP's skin examination repertoire — Elevated, Firm, Growing. Any nodule on sun-exposed skin that is elevated (raised above the skin surface), firm to palpation (unlike the soft consistency of a seborrhoeic keratosis), and growing (patient or GP observes it is larger than a previous examination or photograph) should prompt consideration of a suspected cancer pathway referral (NICE NG12: consider). The EFG rule has been specifically validated for identifying nodular melanoma, which represents the most dangerous subtype due to its rapid vertical growth phase. A GP who applies only ABCDE criteria and 'reassures' a patient with a firm growing skin-coloured or uniformly dark nodule on the nose or ear because it doesn't have irregular borders or multiple colours has missed nodular melanoma. The rule of thumb: any growing nodule on sun-exposed skin in a patient over 50 needs urgent specialist assessment — consider nodular or amelanotic melanoma, SCC, BCC and pyogenic granuloma.