Squamous Cell Carcinoma & Basal Cell Carcinoma
Dermatology · Tumours · lean revision notes
Squamous Cell Carcinoma & Basal Cell Carcinoma
Non-melanoma skin cancers (NMSC) are the commonest malignancies in humans. The two heavyweights — Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC) — together are favourites in NEET PG dermatology and surgery, tested through morphology spotters, premalignant precursors, syndromic associations, and the choice of Mohs micrographic surgery.
Orientation & quick contrast
Both arise from epidermal keratinocytes and are driven overwhelmingly by chronic ultraviolet (UV-B) exposure. The single most useful exam discriminator: BCC is the most common skin cancer overall but almost never metastasises, whereas SCC is the second commonest but has true (though modest) metastatic potential and arises in scars, ulcers, and on mucosa.
| Feature | Basal Cell Carcinoma (BCC) | Squamous Cell Carcinoma (SCC) |
|---|---|---|
| Cell of origin | Basal keratinocytes / hair follicle stem cells | Suprabasal keratinocytes |
| Frequency | Most common skin cancer (~75-80% of NMSC) | Second most common |
| Classic site | Upper face — above a line from angle of mouth to ear lobe | Lower lip, ear, dorsum of hand, scalp, mucosa |
| Typical lesion | Pearly, telangiectatic nodule with rolled edge ("rodent ulcer") | Indurated keratotic nodule / non-healing ulcer with everted edge |
| Precursor | Usually de novo | Actinic keratosis, Bowen's disease, leukoplakia |
| Metastasis | Exceptionally rare (locally invasive) | Definite potential (regional nodes first) |
| Key syndrome | Gorlin (NBCCS), PTCH1 mutation | Xeroderma pigmentosum, epidermodysplasia verruciformis |
| Histology hallmark | Basaloid islands with peripheral palisading + retraction (clefting) artefact | Keratin pearls, intercellular bridges, anaplastic keratinocytes |
High-yield: BCC = "rodent ulcer", pearly + telangiectatic, NEVER metastasises but is locally destructive. SCC = arises in Marjolin's ulcer, lower lip, actinic keratosis, and CAN metastasise.
Etiology & risk factors
Shared driver is cumulative UV radiation, which causes characteristic C→T (and CC→TT) "UV signature" mutations. Important targets:
- BCC → mutations in the Hedgehog (Hh) pathway: loss-of-function in PTCH1 (commonest) or activating mutations in SMO. PTCH1 normally inhibits SMO; loss of PTCH1 releases SMO → constitutive Hh signalling → GLI activation.
- SCC → TP53 (UV signature), plus CDKN2A, RAS, NOTCH1; preceded by a continuum of dysplasia.
Shared risk factors: fair skin (Fitzpatrick I-II), chronic sun exposure, increasing age, arsenic, ionising radiation, immunosuppression.
SCC-specific: Chronic non-healing wounds/scars (Marjolin's), chronic immunosuppression (organ-transplant recipients have a markedly inverted ratio — SCC > BCC, and SCC is far more aggressive), HPV (esp. types 16/18 in genital/periungual SCC), tobacco/areca for oral SCC, epidermodysplasia verruciformis.
High-yield: In organ-transplant / chronically immunosuppressed patients the BCC:SCC ratio reverses — SCC predominates and behaves aggressively. Voriconazole (used post-transplant) further increases SCC risk.
Genodermatoses to memorise
| Syndrome | Gene / defect | Cancer link |
|---|---|---|
| Gorlin (Nevoid BCC) syndrome | PTCH1 (AD), chr 9q22 | Multiple BCCs, odontogenic keratocysts, palmar/plantar pits, calcified falx cerebri, bifid ribs, frontal bossing, medulloblastoma |
| Xeroderma pigmentosum | Nucleotide-excision-repair defect | BCC, SCC, melanoma at young age; photosensitivity |
| Epidermodysplasia verruciformis | EVER1/EVER2 (TMC6/8) | HPV-driven SCC |
| Albinism (OCA) | Tyrosinase/melanin pathway | SCC mainly |
Mnemonic for Gorlin syndrome — "BCC PROBE": Basal cell carcinomas (multiple, young age), Calcification of falx, Cysts (odontogenic keratocysts of jaw), Palmar/plantar pits, Rib anomalies (bifid), Odontogenic tumours, Bossing (frontal) & broad nasal root, Eye/eyebrow anomalies (hypertelorism) + medulloblastoma.
High-yield: Gorlin syndrome = PTCH1 mutation, autosomal dominant. The triad most tested: multiple BCCs + jaw keratocysts + palmar pits with lamellar calcification of falx cerebri on skull X-ray.
Pathophysiology in one flow
UV-B photon → pyrimidine dimer / C→T mutation → driver gene hit → clonal keratinocyte proliferation → invasion.
- BCC route: UV → PTCH1 loss → unopposed SMO → GLI transcription → basaloid tumour islands invading dermis (but tumour cells depend on stroma, hence near-zero metastasis).
- SCC route: UV → p53 inactivation → actinic keratosis (in-situ dysplasia confined to lower epidermis) → Bowen's disease (SCC in situ, full-thickness atypia) → invasive SCC breaching basement membrane → lymphatic spread.
Clinical features
Basal Cell Carcinoma — variants
- Nodular (commonest): the classic pearly, translucent papule/nodule with arborising telangiectasia over the surface and a rolled, raised pearly border; central ulceration = rodent ulcer.
- Superficial: erythematous, scaly plaque with thread-like pearly edge, often on the trunk; can mimic eczema/psoriasis.
- Morphoeic / sclerosing (infiltrative): ill-defined, scar-like, indurated plaque — clinically deceptive, widest subclinical extension → Mohs is preferred.
- Pigmented: brown-black, mimics melanoma (dermoscopy shows blue-grey ovoid nests, leaf-like areas, spoke-wheel structures, arborising vessels).
Squamous Cell Carcinoma — spectrum
- Actinic (solar) keratosis: rough, "sandpaper" erythematous scaly macule on sun-exposed skin — premalignant, low individual risk but a field marker.
- Bowen's disease: well-demarcated erythematous scaly plaque = SCC in situ; on the glans penis it is erythroplasia of Queyrat.
- Invasive SCC: firm, indurated, hyperkeratotic nodule or non-healing ulcer with raised, everted (rolled-out) edges, often tender; bleeds easily. Lower lip and ear are high-risk sites.
- Keratoacanthoma: rapidly growing crateriform nodule with central keratin plug; regarded as a well-differentiated, often self-resolving SCC variant — but treat as SCC.
- Marjolin's ulcer: SCC arising in a chronic wound, burn scar, sinus, or chronic ulcer after a long latency (often >20-30 years).
High-yield: Marjolin's ulcer = SCC in a chronic scar/burn. Suspect it when a long-standing scar shows everted edges, induration, bleeding, foul discharge, or sudden growth. It is typically painless (scar lacks nerves), spreads to regional nodes, but does NOT directly invade because scar tissue is avascular — a classic exam line.
High-yield: Perineural invasion (PNI) in SCC is a marker of aggressive disease — presents with pain, paraesthesia, or facial nerve palsy, predicts recurrence, and is an indication for adjuvant radiotherapy and Mohs surgery.
Diagnosis & investigation of choice
Stepwise approach: Clinical/dermoscopic suspicion → Biopsy (investigation of choice for tissue diagnosis) → Histopathology → Stage if high-risk → Plan excision.
- Definitive diagnosis = skin biopsy with histopathology. Use incisional/punch biopsy for large lesions, excisional biopsy for small ones. For suspected morphoeic BCC or thick SCC, sample to depth.
- Dermoscopy: valuable non-invasive aid (arborising vessels in BCC; glomerular/looped vessels and white circles in SCC).
- Imaging (CT/MRI): reserved for deep/large tumours, suspected bone or perineural involvement, or nodal disease.
- Sentinel lymph node biopsy / FNAC of nodes: for high-risk SCC with suspected regional spread.
SCC histology grading (Broder's)
Broder's classification grades by % of differentiated (keratinising) cells:
| Grade | Differentiated cells | Behaviour |
|---|---|---|
| I | >75% well differentiated | Best prognosis |
| II | 50-75% | Moderate |
| III | 25-50% | Poor |
| IV | <25% (anaplastic) | Worst, most aggressive |
High-yield: Histology of SCC = keratin pearls + intercellular (intercellular bridge) desmosomes + dyskeratotic cells. Histology of BCC = basaloid cells with peripheral palisading and a retraction (clefting) artefact from the stroma.
Management & drug/treatment of choice
Surgical excision is the mainstay for both. Treatment is tailored to risk.
Standard margins
| Tumour | Recommended surgical margin |
|---|---|
| Low-risk BCC | 4 mm clinical margin |
| High-risk / morphoeic BCC | Mohs surgery (or wider margin) |
| Low-risk SCC (<2 cm, well diff) | 4-6 mm |
| High-risk SCC (>2 cm, deep, poorly diff, PNI, recurrent) | 6-10 mm or Mohs |
Mohs micrographic surgery (MMS) — exam darling
A staged excision with complete intra-operative margin assessment of 100% of the deep and peripheral margins using horizontal frozen sections, giving the highest cure rate (~99%) with maximal tissue conservation.
Indications (mnemonic "H-zone, big, bad, back-again"):
- Tumours in the "H-zone" / cosmetically critical, embryonic-fusion areas of the face — nose, eyelids, lips, ears, periorbital, nasolabial folds.
- Recurrent tumours.
- Aggressive histology — morphoeic/infiltrative BCC, poorly differentiated SCC, perineural invasion.
- Large (>2 cm) or ill-defined tumours.
- Tumours in immunosuppressed patients or sites of prior radiotherapy.
High-yield: Mohs micrographic surgery offers the highest cure rate and best tissue conservation; first choice for facial H-zone, recurrent, and morphoeic/high-risk tumours. The principle: margins are checked completely before reconstruction.
Non-surgical / adjunctive options
- Topical 5-fluorouracil or imiquimod → superficial BCC, actinic keratosis, Bowen's disease.
- Cryotherapy / electrodesiccation & curettage → small low-risk superficial lesions.
- Photodynamic therapy → superficial BCC, Bowen's, actinic keratoses (field therapy).
- Radiotherapy → patients unfit for surgery, or adjuvant for PNI/positive margins/incomplete excision.
- Vismodegib / Sonidegib → oral Hedgehog (SMO) inhibitors; drug of choice for locally advanced or metastatic BCC and in Gorlin syndrome with multiple BCCs.
- Cemiplimab (anti-PD-1) → advanced/metastatic cutaneous SCC not amenable to surgery/RT; pembrolizumab also approved.
High-yield: Vismodegib = Hedgehog pathway (SMO) inhibitor → advanced/metastatic BCC and Gorlin syndrome. Cemiplimab (PD-1 inhibitor) → advanced cutaneous SCC. These targeted/immuno agents are increasingly tested.
Complications
- Local tissue destruction: untreated BCC erodes cartilage and bone ("rodent ulcer" gnawing through the nose/orbit) — can be fatal by local invasion of vital structures despite no metastasis.
- Regional & distant metastasis (SCC): lymph nodes first; higher risk with lip/ear primaries, >2 cm size, >4-6 mm depth, poor differentiation, PNI, and immunosuppression.
- Recurrence: especially morphoeic BCC and incompletely excised SCC.
- Perineural spread (SCC): along cranial nerves → palsies and pain.
- Disfigurement / functional loss after wide excision of facial lesions.
- Field cancerisation: multiple synchronous/metachronous tumours on sun-damaged skin → lifelong surveillance.
Key differentials
- BCC vs amelanotic melanoma vs sebaceous hyperplasia vs molluscum (pearly papule).
- Pigmented BCC vs nodular melanoma — dermoscopy + biopsy decide.
- SCC vs keratoacanthoma (KA grows fast, then may involute; histologically overlapping — treat as SCC).
- SCC vs hypertrophic actinic keratosis / Bowen's disease — depth of atypia distinguishes in-situ from invasive.
- Marjolin's ulcer vs simple chronic non-healing ulcer / osteomyelitis sinus — biopsy the everted edge.
- Superficial BCC vs Bowen's disease vs nummular eczema/psoriasis — a "treatment-resistant eczematous plaque" should be biopsied.
Recently asked / exam angle
- Spotter: "Pearly nodule with telangiectasia and rolled margin on the nose of an elderly farmer" → Nodular BCC (rodent ulcer).
- One-liner: "Most common skin cancer" → BCC; "skin cancer that metastasises / arises in scar" → SCC.
- Gorlin syndrome: gene asked = PTCH1; features = jaw keratocysts + palmar pits + falx calcification + multiple BCCs.
- Marjolin's ulcer: SCC in chronic burn scar; classically painless, lymphatic (not haematogenous) spread, slow-growing.
- Mohs surgery indications: facial H-zone, recurrent, morphoeic BCC, perineural SCC — "highest cure rate."
- Drug match: Vismodegib → BCC (Hedgehog/SMO); Cemiplimab → SCC (PD-1); 5-FU/imiquimod → actinic keratosis & superficial BCC.
- Premalignant continuum: actinic keratosis → Bowen's (SCC in situ) → invasive SCC; erythroplasia of Queyrat = Bowen's of glans.
- Histology match: keratin pearls → SCC; peripheral palisading + retraction artefact → BCC.
- Immunosuppression/transplant: SCC > BCC, aggressive — a frequent twist.
- Perineural invasion in SCC → indication for adjuvant radiotherapy.
- Photosensitive child with multiple skin cancers → Xeroderma pigmentosum (NER defect).
Rapid revision
- BCC = commonest skin cancer; SCC = second, but the one that metastasises.
- BCC classic = pearly, telangiectatic, rolled-edge "rodent ulcer" on the upper face.
- SCC classic = indurated non-healing ulcer with everted edges on lip/ear/hand, or in a scar.
- Marjolin's ulcer = SCC in a chronic burn scar/wound; painless, lymphatic spread, long latency.
- Gorlin syndrome = PTCH1 (AD) → multiple BCCs + jaw keratocysts + palmar pits + calcified falx + medulloblastoma.
- BCC driver = Hedgehog pathway (PTCH1 loss → SMO); SCC driver = TP53 + actinic keratosis precursor.
- Investigation of choice = biopsy + histopathology. BCC → peripheral palisading + retraction artefact; SCC → keratin pearls + intercellular bridges.
- Mohs micrographic surgery = highest cure rate, best tissue sparing → facial H-zone, recurrent, morphoeic, perineural tumours.
- Surgical margins: low-risk BCC 4 mm, low-risk SCC 4-6 mm; high-risk → Mohs/wider.
- Vismodegib (SMO inhibitor) → advanced/metastatic BCC & Gorlin; Cemiplimab (anti-PD-1) → advanced SCC.
- Topical 5-FU / imiquimod / PDT → actinic keratosis, Bowen's, superficial BCC.
- Transplant / immunosuppressed → SCC predominates and is aggressive; perineural invasion in SCC → add radiotherapy.