21Non-Melanoma Skin Cancer (basal cell / cutaneous squamous cell)
Snapshot. The commonest cancers in humans — met incidentally, on the face of a patient who came about something else. Two keratinocyte cancers, both UV-driven: BCC (basal cell carcinoma) — the "rodent ulcer": pearly rolled border + central ulceration; locally destructive, almost never metastasises (<0.1%) → cure is local. cSCC (cutaneous squamous cell carcinoma) — faster-growing, does metastasise (~2–5%, nodes first) → stage the nodes. Immunosuppression (transplant) multiplies cSCC risk ~65–100×. Biology: BCC = hedgehog pathway (PTCH1/SMO) — why hedgehog inhibitors work; cSCC = very high UV mutational burden — why immunotherapy works.
Workup
Biopsy — shave or punch (⚠ for a small, well-defined lesion an excisional biopsy is BOTH diagnosis AND definitive treatment — the same one-act-two-jobs logic as TURBT in bladder [§3]) · staging: clinical only for BCC; for cSCC examine the draining nodes ± US/CT if high-risk/node-suspicious · risk-stratify: site (central face/ear/lip — the "H-zone"), size >2 cm, ill-defined borders, recurrence, aggressive histology (BCC morpheaform/infiltrative; cSCC poorly differentiated, perineural invasion, depth >6 mm), immunosuppression · dermoscopy + dermatology referral; DDx = the other keratinocyte cancer, keratoacanthoma, amelanotic melanoma (the dangerous mimic), cutaneous metastasis.
Treatment by setting
| Setting | Treatment |
|---|
| Low-risk, localised | Surgical excision, 4–5 mm margins = the standard Superficial BCC alternatives
topical imiquimod / 5-fluorouracil, cryotherapy, curettage + electrodesiccation |
| High-risk / facial ("H-zone") / recurrent | Mohs micrographic surgery
staged excision with complete margin assessment intra-operatively — highest cure rate and spares the most tissue |
| Radiotherapy | A genuinely curative alternative when surgery isn't
elderly / frail, anticoagulated, cosmetically difficult sites, or refusal Also ADJUVANT after excision
for perineural invasion, positive / close margins, extensive nodal disease ⚠ Avoid in Gorlin syndrome / xeroderma pigmentosum |
🔴 VERY-HIGH-RISK / borderline-resectable
keratoacanthomatous rapid growth, in-transit mets, or surgery alone would cause major functional loss | Neoadjuvant cemiplimab before surgery
NCCN category 2B, both BCC and cSCC — after tumour-board discussion · emerging role, confirm local protocol before use |
| Locally advanced / metastatic BCC | On progression / intolerance → cemiplimab |
| Locally advanced / metastatic cSCC | ⚠ Transplant recipients — IO risks graft rejection
transplant-MDT decision; cetuximab / chemo / RT are the alternatives |
🔴 ADJUVANT — high-risk cSCC
after surgery + radiotherapy | Adjuvant cemiplimab (C-POST)
reduces recurrence/death risk 68% vs placebo (HR 0.32) · FDA-approved Oct 2025, the first adjuvant immunotherapy in this disease · very recent — confirm local NCCN / formulary incorporation before treating |
Watch
BCC = local destruction, not metastasis — the morbidity is what it eats (eye, nose, ear); treat early and completely. cSCC → examine the draining nodes every visit. Perineural invasion = numbness/tingling/facial weakness over the lesion → MRI + adjuvant RT. Hedgehog inhibitors → muscle spasms, dysgeusia, alopecia, weight loss — poorly tolerated long-term; teratogenic (strict contraception). Cemiplimab → irAEs; ⚠ graft rejection in transplant recipients. Field effect: one keratinocyte cancer predicts more — lifelong skin surveillance + sun protection; in transplant patients, switching to an mTOR inhibitor (sirolimus) cuts new cSCC (same lever as Kaposi sarcoma, §19).