Nodular melanoma accounts for approximately 15% of all melanomas but 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 be referred with the same urgency as an ABCDE-positive lesion. 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 should be referred urgently.

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 2WW dermatology 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, improving diagnostic accuracy from approximately 60-70% (clinical examination only) to approximately 80-90% (trained dermoscopy). 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 2WW — 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 equipment investment is modest — a quality polarised light dermoscope costs £200-£400. The RCGP has an accredited dermoscopy learning pathway. For GPs without dermoscopy, TeleDerm (NHS digital teledermatology) allows dermoscopic images to be reviewed remotely by a specialist dermatologist, dramatically reducing face-to-face dermatology referrals.

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) advise patients that the worst part (day 14-21) is the most effective phase and that stopping early reduces efficacy; (3) advise sunscreen on treated areas; (4) advise not applying to periorbital, intertriginous, or mucous membrane areas; and (5) book a review at 4 weeks 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) complete excision of the entire lesion (not punch biopsy or shave); (2) the specimen must be oriented and processed with margins intact; (3) an adequate excision margin (initial excision typically 2 mm margin, with wider re-excision determined by Breslow thickness — <1 mm: re-excision to 1 cm margin; 1-2 mm: 1-2 cm; >2 mm: 2 cm). A GP who excises a suspected melanoma with a 0.5 cm margin has removed the lesion in a way that may be insufficient for staging and may compromise re-excision. The correct primary care action: 2WW referral, not excision.

The Mohs micrographic surgery for facial BCC represents the gold standard for achieving clear surgical margins while minimising tissue removal — it is particularly important 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. This achieves >99% cure rate for primary BCC and >95% for recurrent BCC 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 (confirm it is not melanoma — 2WW) and refer to the appropriate service. Patients with facial BCCs should be referred to a dermatologist or plastic surgeon with Mohs capability where available, particularly for lesions near critical structures.

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 be referred on the 2WW pathway. 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 is a melanoma until a dermatologist says otherwise.