Skin Tumours & Melanoma
Surgery · Oncology · lean revision notes
Skin Tumours & Melanoma
Cutaneous malignancies are a favourite NEET PG zone because they pack named eponyms, crisp clinical signs, and protocol-driven margins. This note walks through the three pillars — basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma — plus benign mimics, with the staging systems and excision margins examiners love.
Classification of skin tumours
Skin tumours are broadly divided into benign, premalignant, and malignant lesions. Malignant tumours are further split into non-melanoma skin cancer (NMSC) — overwhelmingly BCC and SCC — and melanoma, which arises from melanocytes.
| Category | Examples |
|---|---|
| Benign | Seborrhoeic keratosis, dermatofibroma, naevi (moles), keratoacanthoma (self-limiting), pyogenic granuloma |
| Premalignant | Actinic (solar) keratosis, Bowen's disease (SCC in situ), leukoplakia, lentigo maligna (melanoma in situ), xeroderma pigmentosum |
| Malignant — non-melanoma | Basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma |
| Malignant — melanocytic | Malignant melanoma |
High-yield: BCC is the commonest skin cancer overall (and commonest human malignancy in fair-skinned populations); SCC is second. Melanoma is far less common but causes the majority of skin-cancer deaths because of its metastatic potential.
The dominant aetiological driver across all three is ultraviolet (UVB > UVA) radiation. Other risks: fair skin (Fitzpatrick I–II), immunosuppression (organ transplant recipients — SCC risk rises dramatically), chronic non-healing wounds, ionising radiation, arsenic exposure, and genetic syndromes (xeroderma pigmentosum, Gorlin syndrome).
Basal cell carcinoma (BCC)
Pathophysiology & types
BCC arises from the basal layer of the epidermis and its appendages. The key molecular driver is dysregulation of the Hedgehog (Hh) signalling pathway — loss-of-function mutation in the PTCH1 tumour-suppressor gene (or activating SMO mutation), constitutively activating GLI transcription factors. Gorlin (naevoid basal cell carcinoma) syndrome is the autosomal-dominant PTCH1 germline disorder featuring multiple BCCs, odontogenic keratocysts, palmar/plantar pits, and falx calcification.
Morphological subtypes:
- Nodular (commonest) — pearly papule with rolled, raised edges and surface telangiectasia; central ulceration = the classic rodent ulcer.
- Superficial — erythematous scaly plaque, often on trunk; can mimic eczema/psoriasis.
- Morphoeic (sclerosing/infiltrative) — ill-defined, scar-like, aggressive with deep extension; highest recurrence.
- Pigmented — mimics melanoma.
Clinical features
- Most common site: face, above a line from the angle of the mouth to the ear lobe (sun-exposed). The medial canthus is a danger zone for deep invasion.
- Slow-growing, locally invasive, virtually never metastasises (key exam point distinguishing it from SCC and melanoma).
- Telangiectasia over a pearly, translucent nodule with a rolled edge → classic.
High-yield: BCC = locally destructive ("rodent ulcer" gnaws like a rodent) but essentially non-metastasising. SCC metastasises; melanoma metastasises early and widely.
Diagnosis & management
Diagnosis is clinical + dermoscopy (arborising vessels, blue-grey ovoid nests) confirmed by biopsy. Histology: basaloid cells with peripheral palisading and retraction (clefting) artefact from surrounding stroma.
Management flow: Identify subtype/site → low-risk: surgical excision with 3–5 mm margin → high-risk/recurrent/face: Mohs micrographic surgery → not surgical candidate: radiotherapy / topical (imiquimod, 5-FU for superficial) → metastatic/locally advanced: Hedgehog inhibitors (vismodegib, sonidegib).
High-yield: Mohs micrographic surgery gives the highest cure rate with maximal tissue conservation — drug/treatment of choice for high-risk facial BCC (e.g., medial canthus, nasal ala) and recurrent lesions.
Squamous cell carcinoma (SCC)
Pathophysiology
SCC arises from keratinocytes of the stratum spinosum and shows malignant proliferation with keratinisation. Driven by cumulative UV damage causing p53 (TP53) mutations. Precursors and associations:
- Actinic keratosis → SCC in situ → invasive SCC.
- Bowen's disease = SCC in situ (full-thickness dysplasia, intact basement membrane).
- Marjolin's ulcer = aggressive SCC arising in a chronic wound, burn scar, or sinus (classic eponym).
- Immunosuppression (transplant patients), HPV, arsenic, chronic inflammation.
Clinical features
- Sites: sun-exposed areas — lower lip, pinna/ear, dorsum of hand, scalp (bald men).
- Indurated, everted/heaped-up edge ulcer or a keratotic/crusted nodule that grows faster than BCC and may bleed.
- Metastasises via lymphatics — assess regional nodes. High-risk features for metastasis: lip/ear location, size >2 cm, depth >4 mm, poor differentiation, perineural invasion, immunosuppression.
High-yield: Marjolin's ulcer — SCC in a long-standing burn scar/chronic ulcer; it is relatively painless, lacks lymphatic spread early (scar tissue has poor lymphatics) but is aggressive once it does spread. A classic single-best-answer.
Diagnosis & management
Biopsy (incisional/punch) confirms diagnosis: keratin pearls, intercellular bridges, varying differentiation (graded by Broders' grading I–IV).
Management:
- Wide local excision — 4–6 mm margin for low-risk; 6–10 mm for high-risk.
- Mohs surgery for high-risk facial/recurrent SCC.
- Sentinel node biopsy / nodal dissection if regional spread.
- Radiotherapy as adjuvant or for inoperable disease.
- Cemiplimab (anti-PD-1) for advanced/metastatic cutaneous SCC.
Keratoacanthoma (the great mimic)
A rapidly growing, dome-shaped nodule with a central keratin-filled crater, classically appearing over weeks and then spontaneously regressing over months. Histologically and clinically it can be indistinguishable from well-differentiated SCC, so most authorities treat it as a low-grade SCC variant and excise it rather than watch.
High-yield: Keratoacanthoma = "volcano-like" lesion with rapid growth and spontaneous regression — but treat as SCC because of the diagnostic overlap.
Malignant melanoma
Origin & types
Melanoma arises from melanocytes (neural-crest derived) in the basal epidermis. About 70% arise de novo; the rest from pre-existing naevi. CDKN2A germline mutations and BRAF V600E somatic mutations (≈50%) are key — the latter is therapeutically targetable.
| Subtype | Frequency | Key features |
|---|---|---|
| Superficial spreading | Commonest (~70%) | Radial (horizontal) growth phase first; trunk (men), legs (women) |
| Nodular | ~15–20% | Most aggressive; vertical growth from the outset, no radial phase; worst prognosis |
| Lentigo maligna melanoma | ~5–10% | Elderly, sun-damaged face; arises in lentigo maligna; best prognosis |
| Acral lentiginous | ~5% | Palms, soles, subungual; commonest type in dark-skinned/Asian patients |
High-yield: Acral lentiginous is the commonest melanoma in Indians and other pigmented skin; subungual melanoma with periungual pigment spread = Hutchinson's sign.
Clinical features — the ABCDE rule
The classic screening mnemonic for a suspicious pigmented lesion:
- A — Asymmetry
- B — Border irregularity
- C — Colour variegation
- D — Diameter >6 mm
- E — Evolution/Elevation (change over time)
Glasgow 7-point checklist (major: change in size, shape, colour; minor: diameter ≥7 mm, inflammation, oozing/crusting, itch/altered sensation) is the alternative referral tool.
Diagnosis & investigation of choice
- Excisional biopsy with a narrow (2 mm) margin is the investigation of choice — never do an incisional/shave biopsy of suspected melanoma if avoidable, because accurate Breslow thickness needs the full lesion depth.
- Dermoscopy aids selection. Histology + immunohistochemistry: S-100 (most sensitive), HMB-45, Melan-A/MART-1, SOX10.
- Staging workup for thicker lesions: LDH (prognostic — part of M staging), CT/PET-CT, sentinel node biopsy.
Staging: Breslow & Clark
Two named systems — Breslow thickness is the single most important prognostic factor and the one quoted in modern AJCC staging.
| Breslow thickness | T stage (AJCC) | Significance |
|---|---|---|
| ≤1.0 mm | T1 | Excellent prognosis |
| >1.0–2.0 mm | T2 | — |
| >2.0–4.0 mm | T3 | — |
| >4.0 mm | T4 | Poorest prognosis |
Clark's levels describe anatomical depth of invasion (I = epidermis/in situ; II = papillary dermis; III = fills papillary dermis; IV = reticular dermis; V = subcutaneous fat) but are less predictive than Breslow and now largely historical.
High-yield: Breslow > Clark. Breslow (measured in mm from granular layer to deepest tumour cell) drives both prognosis and surgical margin decisions. Memorise it.
Management — wide local excision margins
Definitive treatment after diagnostic excision is wide local excision (WLE), with margins dictated by Breslow thickness:
| Breslow thickness | Recommended WLE margin |
|---|---|
| In situ (melanoma in situ) | 0.5 cm |
| ≤1 mm | 1 cm |
| 1–2 mm | 1–2 cm |
| 2–4 mm | 2 cm |
| >4 mm | 2 cm |
Sentinel lymph node biopsy (SLNB) is offered for melanomas ≥0.8–1.0 mm thick (or thinner with ulceration/high mitotic rate). It is staging/prognostic; a positive node prompts consideration of completion lymphadenectomy vs nodal surveillance plus systemic therapy.
Stepwise approach: Suspicious lesion → excisional biopsy (2 mm) → Breslow + ulceration + mitoses → WLE with margin per thickness → SLNB if ≥0.8–1 mm → node-positive or metastatic → systemic therapy (immunotherapy ± targeted therapy).
Systemic therapy (immunotherapy & targeted agents)
Metastatic/advanced melanoma management has been transformed:
- Immune checkpoint inhibitors: ipilimumab (anti-CTLA-4), nivolumab / pembrolizumab (anti-PD-1). Combination ipilimumab + nivolumab gives the best response in advanced disease at the cost of toxicity.
- BRAF-targeted therapy (for BRAF V600E-mutant tumours): BRAF inhibitor (vemurafenib/dabrafenib) plus MEK inhibitor (trametinib/cobimetinib).
- Melanoma is classically radioresistant and chemoresistant (dacarbazine historically used, now largely superseded).
High-yield: Ipilimumab = anti-CTLA-4; nivolumab/pembrolizumab = anti-PD-1. BRAF V600E mutation → BRAF + MEK inhibitor combination. These pairings are repeatedly tested.
Complications
- BCC: local tissue destruction, invasion of cartilage/bone (especially morphoeic, medial canthus), disfigurement; recurrence.
- SCC: regional lymph node and distant metastasis, perineural invasion, recurrence in immunosuppressed patients.
- Melanoma: early haematogenous and lymphatic spread to liver, lung, brain, bone; in-transit and satellite metastases; high recurrence; immunotherapy-related immune adverse events (colitis, hypophysitis, thyroiditis, dermatitis, hepatitis).
Key differentials
- Pearly papule with telangiectasia → BCC vs intradermal naevus vs sebaceous hyperplasia.
- Keratotic ulcer with everted edge → SCC vs keratoacanthoma vs amelanotic melanoma.
- Pigmented lesion → benign naevus vs seborrhoeic keratosis vs pigmented BCC vs melanoma (use ABCDE/dermoscopy).
- Subungual pigment → subungual melanoma vs subungual haematoma (haematoma migrates distally with nail growth; melanoma shows Hutchinson's sign and persistent proximal pigment).
| Feature | BCC | SCC | Melanoma |
|---|---|---|---|
| Cell of origin | Basal keratinocyte | Spinous keratinocyte | Melanocyte |
| Edge/appearance | Rolled pearly, telangiectasia, rodent ulcer | Everted/heaped keratotic ulcer | Pigmented ABCDE lesion |
| Metastasis | Almost never | Lymphatic (moderate) | Early, lymphatic + haematogenous |
| Key driver | PTCH1 / Hedgehog | TP53 / UV | BRAF V600E, CDKN2A |
| Treatment of choice | Excision / Mohs (high-risk) | WLE / Mohs ± nodes | WLE per Breslow + SLNB |
| Advanced systemic | Vismodegib | Cemiplimab | Ipilimumab/nivolumab; BRAF+MEK |
Recently asked / exam angle
- Breslow vs Clark — which is more prognostic? (Answer: Breslow thickness.)
- WLE margin for a 2 mm melanoma → 2 cm (margin matching exercises are common).
- Ipilimumab mechanism = anti-CTLA-4; nivolumab/pembrolizumab = anti-PD-1.
- Rodent ulcer = BCC; commonest skin cancer overall.
- Marjolin's ulcer = SCC in a chronic burn scar.
- Hutchinson's sign = periungual/nail-fold pigment spread in subungual melanoma (do not confuse with Hutchinson's sign of herpes zoster on the nose tip — both names exist!).
- Commonest melanoma overall = superficial spreading; most aggressive = nodular; commonest in dark skin = acral lentiginous.
- Most sensitive melanoma marker = S-100; more specific = HMB-45.
- Biopsy of choice for suspected melanoma = excisional (not incisional/shave).
- Gorlin syndrome = PTCH1, multiple BCCs + jaw keratocysts + palmar pits.
- Melanoma is radioresistant and chemoresistant — image-style "best initial systemic therapy" now points to immunotherapy.
Rapid revision
- BCC = commonest skin cancer; "rodent ulcer", pearly rolled edge + telangiectasia; rarely metastasises; driver = PTCH1/Hedgehog.
- Mohs surgery = highest cure + tissue-sparing for high-risk facial/recurrent BCC; vismodegib for advanced BCC.
- SCC = everted keratotic ulcer; metastasises via lymphatics; precursors = actinic keratosis, Bowen's disease.
- Marjolin's ulcer = SCC in chronic burn scar/sinus; cemiplimab for advanced SCC.
- Keratoacanthoma = rapid "volcano" crateriform lesion, regresses spontaneously, but excise (mimics SCC).
- Melanoma screening = ABCDE (Asymmetry, Border, Colour, Diameter >6 mm, Evolution).
- Excisional biopsy is the diagnostic procedure of choice for suspected melanoma — preserves Breslow depth.
- Breslow thickness = single most important prognostic factor; outranks Clark's level.
- WLE margins: in situ 0.5 cm; ≤1 mm → 1 cm; 1–2 mm → 1–2 cm; >2 mm → 2 cm.
- SLNB for melanoma ≥0.8–1.0 mm (or thinner if ulcerated/high mitotic rate).
- Acral lentiginous = commonest melanoma in Indians; Hutchinson's sign in subungual melanoma; S-100 most sensitive marker.
- Ipilimumab = anti-CTLA-4; nivolumab/pembrolizumab = anti-PD-1; BRAF V600E → BRAF + MEK inhibitor; melanoma is radio- and chemo-resistant.