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Mateusz Gładysz

Pathway read-through · Cutaneous squamous cell carcinoma

Cutaneous SCC: four factors, and who counts them

Mateusz Gładysz · MD · FEBOPRAS · FEBHS

A read-through for a New Zealand regional melanoma and high-risk skin cancer MDM, for the registrar preparing a cutaneous SCC case and the consultant chairing it. The core line carries the decisions; the closed panels carry the groundwork and the divergences.

Clinical content verified References checked 53 questions 8 MDM cases Version 1.1

All cases are constructed for teaching and describe no real patient. Clinical content verified 1 October 2026. Sources: NZSCD SCC and BCC Guidelines 2023 (high-risk criteria; follow-up), linked by Skin Cancer NZ · Te Aho o Te Kahu MDM standards (March 2024) · Pharmac Schedule October 2026 · CCA keratinocyte cancer guideline v1.4 (MAGICapp, 19 April 2024; NHMRC approval 2019) · NCCN Squamous Cell Skin Cancer v2.2026 (tables quoted from a redraw on a manufacturer-hosted portal) · EADO/EDF/ESTRO cSCC guideline Update 2026, Parts 1–2 (abstracts and extracted fragments; full text paywalled, so recommendation wording, grades and figures beyond the abstracts were not re-checked against it) · BAD 2020 (from secondary summaries) · AJCC 8th ed. · BWH staging.

Scope: non-head-and-neck cSCC. In this read-through, the MDM’s terms of reference send head and neck cSCC to a separate Head and Neck MDM and exclude simple cSCC; check your own MDM’s terms of reference. Head and neck cSCC appears here only as a routing decision. Not covered: mucosal, eyelid and anogenital SCC; BCC; Merkel cell carcinoma.

Skip to MDM cases
SchemaFour features invisible in clinic carry cSCC risk; the system that counts them decides how many patients are worked up.
Changes in practice since January 2025
  • 2025 — C-POST published (Rischin, NEJM 2025;393:7741): adjuvant cemiplimab after surgery and postoperative radiotherapy in high-risk cSCC, disease-free survival HR 0.32; overall survival immature.
  • ASCO 2025 — KEYNOTE-6302 (adjuvant pembrolizumab after surgery and radiotherapy) negative: recurrence-free survival HR 0.76, P = 0.072; overall survival HR 1.47 (0.87–2.48). Stopped for futility.
  • October 2025 — US FDA approves cemiplimab as adjuvant treatment for cSCC at high risk of recurrence after surgery and radiotherapy. Not a Medsafe-approved indication.
  • February 2026 — NCCN Squamous Cell Skin Cancer v1.2026 adds an “extremely high risk” group and lists adjuvant cemiplimab after surgery and radiotherapy as category 1 preferred for it; neoadjuvant cemiplimab may be considered in selected very-high-risk cases.
  • May 2026 — EADO/EDF/ESTRO cSCC guideline Update 2026 (Eur J Cancer 243:116763–4): the decision on adjuvant cemiplimab for cSCC at high risk of recurrence after surgery and radiotherapy is to be made in the multidisciplinary tumour board (abstract; the full recommendation wording and grade were not verified because the full text is paywalled); low-risk margin 4–6 mm (reported in the 2026 update; full text not re-checked); new “difficult-to-treat” groups.
  • 11 September 2026 — Pharmac publishes the November 2026 CTAC agenda: an application for first-line cemiplimab in advanced cSCC (P-001628) will be considered. No recommendation or decision yet.

WorkupWhich MDM, and is the report enough to decide?

Basics: what this MDM sees, and what a cSCC report contains

In this read-through the MDM takes non-head-and-neck cSCC; head and neck cSCC goes to the Head and Neck MDM. Te Aho o Te Kahu’s 2024 standards exclude simple SCC and BCC from MDMs altogether, so what arrives here should be a trunk or limb tumour with a reason to discuss it.

A cSCC report (RCPath dataset) gives: specimen type; clinical diameter from the request form; thickness in mm measured from the granular layer of the adjacent normal epidermis; whether invasion goes beyond subcutaneous fat; differentiation, graded by the worst area; subtype (acantholytic, adenosquamous, spindle, desmoplastic); PNI with calibre, depth and number of nerves; LVI; bone invasion; peripheral and deep margins in mm. Clark level is not a cSCC staging item.

Case
Three cSCC referrals reach a regional Melanoma & HRSC MDM coordinator. Under the terms of reference assumed in this read-through, where should each be discussed?
□ Guess   □ Fairly sure   □ Certain
Head and Neck MDM. The temple is head and neck skin; under the stated terms of reference, head and neck cSCC goes there whatever its risk.
No MDM. Small, thin, well differentiated and excised: a simple cSCC, which Te Aho o Te Kahu excludes from MDMs.
This MDM. Trunk or limb, >4 cm and beyond fat: NCCN very high risk and BWH T2b (size, depth).
Routing turns on two facts: site and complexity. Head and neck cSCC goes to the Head and Neck MDM even when it is very high risk. A simple trunk or limb cSCC needs no MDM. What remains for this MDM is the non-head-and-neck tumour with high-risk features, nodal or in-transit disease, immunosuppression, or a radiotherapy or systemic-therapy question.

Rule

This MDM discusses non-head-and-neck cSCC; scalp, face, ear, lip and neck tumours go to the Head and Neck MDM. Simple cSCC comes to neither. Te Aho o Te Kahu does not define “simple”; the working threshold used here follows the CCA referral triggers: diameter >2 cm, depth >4 mm, recurrence, high-risk site, or LVI, poor , immunosuppression. Add any nodal or in-transit disease and any question of radiotherapy or systemic therapy.

Simple non-melanoma skin cancers (SCC/BCC) are excluded. … The specific referral criteria for each MDM will be included in their TOR.

Source: Te Aho o Te Kahu, Standards for high-quality cancer MDMs in Aotearoa NZ (March 2024)3, Quality Area 4; CCA keratinocyte cancer guideline v1.44, PP 11.7.1 (referral triggers).

Rule

Risk is decided on the report, not in clinic. Before discussion confirm it states thickness in mm, whether invasion goes beyond subcutaneous fat, differentiation by the worst area, subtype, PNI calibre, depth and number, LVI and margins in mm; the referrer supplies the clinical diameter measured before biopsy. A shave or base-transected specimen cannot give thickness or level: the action is a complete excision, not a stage.

Excision biopsy should be performed when appropriate. If complete excision is not possible, punch biopsies, shave biopsy or curettage can be considered, as appropriate to the size and depth of the lesion.

Source: CCA keratinocyte cancer guideline v1.44, PP 9.5.1; RCPath cSCC dataset5 items; NCCN Squamous Cell Skin Cancer v2.2026 table footnote: “Preoperative clinical tumor diameter.”

Worked case — 5 steps
ReferralExcision, left shin, 77-year-old woman. Report: invasive SCC, moderately differentiated, thickness 5.2 mm, “PNI present”, margins clear (peripheral 3 mm, deep 1 mm). Clinical diameter not recorded on the request form. Immunocompetent.
  1. WorkupRoute: lower limb, so this MDM. Pretibial skin is an NCCN high-risk site at any size; it is not head and neck.
  2. WorkupTwo BWH inputs are missing: PNI calibre and the clinical diameter. Without them the BWH count could be anywhere from zero to two.
  3. StagingProvisional NCCN tier: at least high risk. Pretibial site and 2–6 mm depth; the missing items can only raise it.
  4. WorkupAsk the pathologist for PNI calibre, depth and number; ask the referrer for the pre-excision diameter or photograph. CCA: discuss reported PNI with the pathologist.PP 11.5.1
  5. TreatmentDefer the adjuvant radiotherapy decision until both return. A nerve >0.1 mm would add a BWH factor and make surgery plus RT the CCA recommendation.EBR 11.7.2
What would change this? An addendum reading “one dermal nerve, 0.05 mm” with a 15 mm diameter makes this BWH T1, NCCN high risk by site and depth, with no radiotherapy question.

Why?

Why is differentiation graded by the worst area rather than the predominant one?

Show answer
The tumour’s behaviour is set by its most aggressive component, not its average. RCPath grades a tumour by its most poorly differentiated region, whatever its extent, and notes that NCCN does the same, so grading by the predominant pattern would under-call the tumours most likely to metastasise. The same logic explains why a small incisional biopsy can under-grade: it may not contain the worst area.
Evidence and other guidelinesNCCN ≠ CCA on biopsy depth

Biopsy. NCCN (v1.2026 onward): biopsies “should include deep reticular dermis if the lesion is suspected to be more than a superficial process”; if an incisional biopsy seems inadequate for microstaging, “consider narrow margin excisional biopsy”. CCA accepts punch, shave or curettage when excision is not possible (PP 9.5.1). NZSCD 2023: biopsy any lesion “where a biopsy result may change clinical management.” EADO 2026 asks for the clinical diameter to be recorded before biopsy.

Report datasets. EADO 2026 Table 2 (extracted fragment): thickness “from granular layer to deepest point”, invasion beyond fat, PNI “(nerve caliber ≥0.1 mm or extensive)”, , LVI, deep and lateral margins. RCPath advises that Clark level not be used for cSCC and defines desmoplasia as more than 30% of the stroma. Crateriform tumours are measured from the base of the crater (Fernandez-Flores method) so that depth is not over-reported.

Routing. Referral criteria sit in each MDM’s terms of reference (Te Aho o Te Kahu, Quality Area 4) and may differ between regions; the 2024 national exclusion of simple SCC applies to all of them. No national keratinocyte cancer MDM criteria exist. NZSCD: “Refer to your regional Cutaneous Oncology MDM for consideration of clinical trials or novel therapies for advanced disease or in the adjuvant setting.”

TNM9. UICC 9th edition changed skin staging only by adding lip vermilion and commissure to head and neck skin and by clarifying the deep-invasion and PNI definitions. Nothing changes for trunk or limb tumours.

StagingHow many BWH factors, and what does the count change?

Basics: the BWH factors and the NCCN risk table

BWH (Brigham and Women’s Hospital) staging counts four tumour factors: diameter ≥2 cm, poor differentiation, PNI in a nerve ≥0.1 mm, and invasion beyond subcutaneous fat. T1 has none, T2a one, T2b two or three, T3 all four or bone invasion. It was derived and validated on tumours from all body sites.

The NCCN table is a separate tool with three tiers (low, high, very high). It adds site, thickness in mm, recurrence, immunosuppression, prior radiotherapy or chronic inflammation, rapid growth, neurological symptoms, subtype and LVI, and assigns the tier from the single highest factor. It sets treatment intensity; estimates metastasis and death.

Case
Three excised trunk and limb cSCCs; nodes impalpable; patients immunocompetent. What is each BWH T stage?
□ Guess   □ Fairly sure   □ Certain
T2a. One factor, diameter ≥2 cm. The 3 mm thickness is an NCCN input, not a BWH factor.
T2b. Three factors (size, differentiation, depth beyond fat). T2b covers two or three; T3 needs all four.
T3. Bone invasion alone makes T3, whatever the count.
BWH counts four factors and nothing else: diameter ≥2 cm, poor differentiation, PNI in a nerve ≥0.1 mm, invasion beyond subcutaneous fat. Thickness in millimetres, site and immunosuppression are NCCN factors, not BWH factors. T2b is two or three factors; T3 is four, or bone invasion.

Rule

BWH stage is a count, and the count tracks the 5-year risk of nodal metastasis: one factor 3.6%, two 11%, three 20%, four 28%. Against a 10% threshold for looking at the nodes, the crossing is at two factors, which is where T2b begins. cSCC staging is written for head and neck primaries; UICC TNM 8/9 has a separate carcinoma-of-skin chapter for other sites with the same T thresholds. For trunk and limb cSCC, record the UICC T category the report prints and the BWH T stage; BWH discriminates better where the two have been compared (next section).

Source: Jambusaria-Pahlajani A et al., JAMA Dermatol 2013;149:4026 (derivation); Karia PS et al., J Clin Oncol 2014;32:3277 (validation, n = 1,818). Nodal risk by factor count: Ran NA et al., JAMA Dermatol 2025;161:5978. UICC TNM 8 carcinoma of the skin: RCPath cSCC dataset5, Appendix A.

Rule

FactorHighVery high
Size, siteTrunk or limb >2–4 cm; head, neck, hands, feet, pretibial, anogenital (any size)>4 cm, any site
Depth2–6 mm, not beyond fat>6 mm or beyond fat
Differentiation—Poor
PNIPresentNerve deeper than dermis or ≥0.1 mm
LVI—Present
OtherRecurrent, immunosuppressed, prior RT or chronic inflammation, rapid growth, neurological symptoms, poorly defined—

Low risk: trunk or limb ≤2 cm, <2 mm, well or moderately differentiated, primary, none of the above. The tier is set by the highest single factor.

Risk category assignment should be based on the highest risk factor present. High-risk: ↑ risk of local recurrence; very-high-risk: ↑ risk local recurrence and metastasis.

Source: NCCN Squamous Cell Skin Cancer v2.2026, stratification table and footnote, as reproduced in a redraw on a manufacturer-hosted portal (Catalyst, Regeneron; April 2026). NZSCD 2023 high-risk criteria9 include “Depth >6mm or into subcutaneous fat.”

BWH T2aone factorBWH T2btwo or three factors
5-year nodal metastasis risk3.6%11–20%
Nodal imagingExamination; imaging only if another triggerImaging of the draining basin
Sentinel nodeNot discussedDiscussed as an option; no survival benefit shown
Follow-up (NZSCD)High-risk schedule if any NZSCD criterionSame
Check
Which row changes management between BWH T2a and T2b?
□ Guess   □ Fairly sure   □ Certain
✓ (a) Correct. Two factors is the first count above 10% nodal risk, so the basin is examined and imaged.
✗ (b) Both usually meet an NZSCD high-risk criterion; the schedule does not separate them.
✗ (c) It differs, but it is a probability, not a decision. The decision it drives is the imaging row.
Bar chart of 5-year risk of nodal metastasis by the number of Brigham and Women's Hospital factors present. One factor, BWH T2a: 3.6 percent. Two factors, BWH T2b: 11 percent. Three factors, BWH T2b: 20 percent. Four factors, BWH T3: 28 percent. A dashed line at 10 percent is crossed first at two factors, where T2b begins. T1 has no factors. T3 also includes any tumour with bone invasion. The four factors are diameter of 2 cm or more, poor differentiation, perineural invasion of a nerve 0.1 mm or larger, and invasion beyond subcutaneous fat. BWH counts four factors: diameter ≥2 cm · poor differentiation · PNI in a nerve ≥0.1 mm · invasion beyond subcutaneous fat 5-year nodalmetastasis 10% 3.6% 11% 20% 28% 1 factorT2a 2 factorsT2b 3 factorsT2b 4 factorsT3 (or bone) T1 = no factor Risk per count: Ran 2025. BWH counts four factors: diameter ≥2 cm · poor differentiation · PNI in a nerve ≥0.1 mm · invasion beyond subcutaneous fat 5-year nodal metastasis 10% 3.6% 1 factor T2a 11% 2 factors T2b 20% 3 factors T2b 28% 4 factors T3 (or bone) T1 = no factor Risk per count: Ran 2025.
Two factors is the first count above 10%, which is where BWH T2b begins.
Worked case — 5 steps
Referral58-year-old man, lower back. Excision: invasive SCC, clinical diameter 32 mm, poorly differentiated, 4.5 mm thick, confined to dermis and fat, no PNI, no LVI, margins clear. Nodes impalpable. Immunocompetent.
  1. StagingBWH T2b: two factors. ≥2 cm and poor differentiation. The 4.5 mm thickness is not a BWH factor.
  2. StagingNCCN very high risk. Poor differentiation alone sets the tier under the highest-factor rule.
  3. Staging5-year nodal metastasis risk about 11%: examine and image the draining basins. Two factors is above the 10% line.
  4. TreatmentAdjuvant radiotherapy to the primary: consider, not mandate. CCA lists poorly differentiated tumour among the PORT triggers; no other trigger is present.PP 12.3.3
  5. Follow-upNZSCD high-risk schedule: 3–6-monthly for 2 years, 6-monthly for 3 years, then annually for life; nodes examined each visit. CCA sets the first review at 3 months.PP 19.1.2
What would change this? A moderately differentiated tumour of the same size is BWH T2a and NCCN high risk: one factor, nodal risk 3.6%, examination without imaging.

Why?

Why does one very-high-risk feature set the NCCN tier, when BWH needs two factors before nodal risk passes 10%?

Show answer
The tools answer different questions. The NCCN table sets treatment intensity, chiefly margin and margin control, and one feature such as depth >6 mm is enough to raise the risk of local recurrence. BWH estimates metastasis and death, where single factors carry modest absolute risk and co-occurring factors compound it. A tumour can therefore need margin control and still carry a low nodal risk.
Evidence and other guidelinesNCCN 2 mm ≠ BAD 4 mm

Thickness. Brantsch 200810 (prospective, n = 615, complete margin control, median follow-up 43 months): no metastases at ≤2.0 mm; 4% (12/318) at 2.1–6.0 mm; 16% (14/90) above 6.0 mm. Thickness HR 4.79 for metastasis and 6.03 for local recurrence; HR 16.11 (6.57–39.49) for local recurrence. NCCN cuts at 2 and 6 mm; BAD’s low-risk ceiling is 4 mm; CCA uses depth >4 mm as a referral trigger (PP 11.7.1) and >2 mm as a risk factor in its quick reference guide. A 3 mm tumour is NCCN high risk and BAD low risk.

Single factors (Thompson 201611 meta-analysis, 36 studies, 23,421 tumours, low-to-moderate quality): beyond fat, metastasis RR 11.21; diameter ≥2 cm, metastasis RR 6.15 and disease-specific death RR 19.10 (5.80–62.95); poor , metastasis RR 4.98; , metastasis RR 2.95. Local recurrence at >2 mm: RR 9.64 (1.30–71.52). was excluded.

Other lists. NZSCD 2023 adds age <25, origin in a scar, radiotherapy field or chronic inflammation, neurological symptoms, lymphadenopathy, tethering, “discohesive or infiltrating margin”, and acantholytic, adenosquamous, metaplastic and desmoplastic subtypes; it is based on NCCN v1.2023, the CCA keratinocyte cancer guideline (NHMRC approval 2019) and the 2017 AJCC Staging Manual. EADO 2026: diameter >20 mm; lip, ear or temple; thickness >6 mm; beyond fat; bone erosion; desmoplasia or LVI; poor differentiation; immunosuppression; PNI.

Status of the NCCN table. The v2.2026 wording is from a manufacturer-hosted redraw that omits the subtype footnote (v1.2024: acantholytic, adenosquamous and metaplastic high; desmoplastic very high).

StagingThe report prints an AJCC stage. Does it apply?

Basics: where AJCC 8 cSCC staging sits and what it counts

AJCC 8 cSCC staging is printed in the head and neck section of the manual and applies to head and neck primaries. Eyelid, vulvar, penile and perianal SCC have their own chapters. There is no T category for a trunk or limb cSCC. UICC TNM 8/9, which the RCPath dataset uses, does have a carcinoma-of-skin chapter for those sites with the same T thresholds (T1 ≤20 mm; T2 >20–40 mm; T3 >40 mm, or smaller with deep invasion, specified PNI or minor bone erosion), so a pT category printed for a limb tumour is usually the UICC category (RCPath cSCC dataset5, Appendix A).

AJCC 8 head and neck T categories: T1 <2 cm; T2 2–4 cm; T3 ≥4 cm, minor bone erosion, or deep invasion; T4 gross bone or skull base invasion. counts factors instead of applying thresholds in sequence.

Case
Excision, forearm, 69-year-old man: invasive SCC, 30 mm, poorly differentiated, 3.5 mm thick, dermis only, no PNI. The synoptic report prints “pT2 (AJCC 8)”.
Which T classification should the MDM record?
□ Guess   □ Fairly sure   □ Certain
✗ (a) Differentiation is not an AJCC 8 T variable, and AJCC 8 does not apply to the forearm.
✗ (b) Poor differentiation is one of the four BWH factors; two factors make T2b.
✗ (c) AJCC 8 does not cover the forearm; a printed pT2 is the UICC TNM category (>2–4 cm) and carries little prognostic discrimination here. Record BWH alongside it.
✓ (d) Correct. ≥2 cm and poor differentiation. BWH was derived and validated on all-site cohorts.
AJCC 8 cSCC staging sits in the head and neck section of the manual, so a trunk or limb tumour has no AJCC 8 T category. A pT category printed for it is usually the UICC TNM category, which uses the same size thresholds as AJCC 8 and does not count differentiation. Record it alongside the BWH T stage, which counts differentiation and discriminates better where the two have been compared.

Rule

For trunk and limb cSCC, record the BWH T stage and the NCCN tier alongside the UICC T category the report prints; AJCC 8 has no category for these sites. Where the two systems can be compared, in head and neck cSCC, BWH flags half as many patients for the same number of metastases and deaths:

High T classAJCC 8 T3/T4BWH T2b/T3
Patients flagged (of 680)121 (18%)63 (9%)
Metastases / deaths captured17 / 1116 / 12
Sensitivity78%73% (P = .20)
Specificity85%93% (P < .001)
PPV / NPV17% / 99%30% / 99%

Source: AJCC Cancer Staging Manual 8th ed., Head and Neck section; Ruiz ES, Karia PS, Besaw R, Schmults CD. JAMA Dermatol 2019;155:81912, Table 4 of the full text; the abstract gives only the counts and the BWH specificity and PPV (head and neck cSCC, n = 680; outcome nodal metastasis or disease-specific death).

Two proportional bars, each representing the same 680 head and neck cutaneous squamous cell carcinomas (Ruiz 2019, Table 4). AJCC 8 T3 or T4 flagged 121 patients, 18 percent, and captured 17 nodal metastases and 11 disease-specific deaths; sensitivity 78 percent, specificity 85 percent, positive predictive value 17 percent, negative predictive value 99 percent. BWH T2b or T3 flagged 63 patients, 9 percent, and captured 16 nodal metastases and 12 deaths; sensitivity 73 percent, specificity 93 percent, positive predictive value 30 percent, negative predictive value 99 percent. AJCC 8 cSCC staging applies to the head and neck only; BWH applies at all sites. Same 680 head and neck cSCC, two definitions of a high T stage AJCC 8T3/T4 680 patients 121 flagged (18%) → 17 metastases, 11 deaths captured sensitivity 78% · specificity 85% · PPV 17% · NPV 99% BWHT2b/T3 680 patients 63 flagged (9%) → 16 metastases, 12 deaths captured sensitivity 73% · specificity 93% · PPV 30% · NPV 99% Shaded length = patients flagged. Ruiz 2019, Table 4. AJCC 8 cSCC staging covers the head and neck only; for trunk and limb tumours record the UICC T category and the BWH T stage. Same 680 head and neck cSCC, two definitions of a high T stage AJCC 8 T3/T4 680 patients 121 flagged (18%) → 17 metastases, 11 deaths captured sensitivity 78% · specificity 85% · PPV 17% · NPV 99% BWH T2b/T3 680 patients 63 flagged (9%) → 16 metastases, 12 deaths captured sensitivity 73% · specificity 93% · PPV 30% · NPV 99% Shaded length = patients flagged. Ruiz 2019, Table 4. AJCC 8 cSCC staging covers the head and neck only; for trunk and limb tumours record the UICC T category and the BWH T stage.
Half the patients flagged, the same metastases found.
Worked case — 5 steps
Referral76-year-old man with two excised cSCCs, margins clear, nodes impalpable. Scalp: 42 mm, well differentiated, 3 mm, dermis only. Upper back: 42 mm, well differentiated, 3 mm, dermis only.
  1. WorkupScalp tumour to the Head and Neck MDM; back tumour here. Routing follows site, not stage.
  2. StagingScalp: AJCC 8 T3. Back: no AJCC 8 category; UICC TNM T3. AJCC 8 T3 includes a diameter of 4 cm or more; UICC T3 a diameter over 40 mm.
  3. StagingBoth: BWH T2a and NCCN very high risk. One BWH factor (≥2 cm); >4 cm is very high risk at any site.
  4. StagingBWH T2a carries a 5-year nodal metastasis risk of about 3.6%. AJCC 8 T3 puts the scalp tumour in a group with a PPV of 17% for metastasis or death.
  5. Follow-upBoth: NZSCD high-risk schedule. Diameter >2 cm is an NZSCD high-risk criterion.
What would change this? Poor differentiation in the back tumour would make it BWH T2b, above the 10% nodal line.

Why?

Why did AJCC 8, correcting AJCC 7, end up flagging twice as many head and neck patients as BWH?

Show answer
AJCC 7 required bone invasion for T3/T4, so it captured 0.3% of cases and left 86% of poor outcomes in T1/T2. AJCC 8 made several single features each sufficient for T3: diameter ≥4 cm, PNI, deep invasion. Each alone carries modest risk, so T3 filled with patients unlikely to relapse. BWH requires factors to co-occur, which is where the risk concentrates.
Evidence and other guidelinesBoth omit desmoplasia

Ruiz 2019. AJCC 8 T2 and T3 together were 23% of the cohort with overlapping outcomes; the authors call that “too large of a group for routine nodal staging or consideration of adjuvant therapy”. BWH concordance statistics were higher for nodal metastasis and disease-specific death, not for local recurrence or overall survival. The comparison is head and neck only; it cannot be repeated for trunk and limb, where AJCC 8 has no category.

History. AJCC 7 T3/T4 required bone invasion and captured 0.3% of a validation cohort, leaving 86% of poor outcomes in T1/T2.

What both omit. Desmoplasia: local recurrence HR 16.11 in Brantsch10, the largest single figure in that analysis. NCCN (v1.2024 subtype list) places desmoplastic cSCC in the very-high tier. If the report says desmoplastic, the BWH stage understates the tumour.

PNI definitions differ. BWH counts calibre only (≥0.1 mm). AJCC 8 T3 counts a nerve “lying deeper than the dermis or measuring 0.1 mm or larger in caliber” or clinical or radiographic named-nerve involvement. The same report can carry PNI in one system and not in the other.

EADO 2026 names AJCC 8 and BWH as the more widely used systems without restricting AJCC 8 to the head and neck in its abstract. UICC TNM9 does not change trunk or limb staging.

Workup“PNI present”: which PNI?

Basics: what the pathologist measures when reporting perineural invasion

Incidental (microscopic) PNI is found on the slides in a patient without symptoms. The report should give the calibre of the largest involved nerve (above or below 0.1 mm), its depth (dermal, or deeper), the number of nerves involved, and whether a named nerve is involved or the is at a margin.

Clinical PNI means symptoms or signs in a nerve distribution: pain, paraesthesia, numbness, weakness. It implies spread along the nerve, which may extend well beyond the visible tumour, and is assessed with MRI.

Case
Excision, forearm, 64-year-old woman: 15 mm well-differentiated cSCC, 1.8 mm thick, margins 5 mm clear. Report: “microscopic PNI of a single dermal nerve, 0.04 mm”. No other risk feature. No neurological symptoms.
What does the evidence support for the PNI?
□ Guess   □ Fairly sure   □ Certain
✗ (a) CCA recommends surgery plus RT for a nerve >0.1 mm; BAD recommends strongly against RT for excised small dermal PNI. This nerve is 0.04 mm.
✗ (b) Margins are clear and the PNI lies inside the specimen; no guideline widens a clear margin for small dermal PNI.
✓ (c) Correct. Small-calibre dermal PNI in a small, thin, excised tumour: no BWH factor, below the CCA 0.1 mm trigger, and BAD advises against RT. NZSCD lists any PNI as high risk and says to consider adjuvant RT without a calibre threshold; the decision not to irradiate a sub-0.1 mm dermal nerve rests on BAD and the CCA 0.1 mm trigger, so record that reasoning.
✗ (d) MRI is for clinical PNI: pain, numbness or weakness. None is present.
PNI is a compound variable: calibre, depth, number of nerves and clinical signs. A single sub-0.1 mm dermal nerve in a small, thin, excised tumour adds no BWH factor and triggers radiotherapy under none of CCA, NCCN or BAD. NZSCD lists any PNI as high risk and says to consider adjuvant radiotherapy for it, “especially in high risk locations”, with no calibre threshold; not irradiating rests on BAD and the CCA trigger. In the series behind the BAD position, only one local recurrence occurred where nerve invasion was the sole risk factor.

Rule

Before acting on “PNI present”, obtain calibre, depth, number of nerves and named-nerve involvement from the pathologist, and symptoms from the referrer. PNI in a nerve ≥0.1 mm or deeper than the dermis is a factor (calibre) and an NCCN very-high-risk feature, and CCA recommends surgery plus radiotherapy. Small-calibre dermal PNI in an otherwise low-risk, completely excised tumour is not an indication for radiotherapy under BAD or CCA; NZSCD lists any PNI as high risk without a calibre threshold, so record the reasoning.

For tumours with perineural invasion, the combination of surgery and radiotherapy is recommended when a nerve with diameter >0.1mm is involved.

Source: CCA keratinocyte cancer guideline v1.44, EBR 11.7.2 (Grade C); PP 11.5.1: discuss reported PNI with the pathologist. BAD 202013: strong recommendation against adjuvant RT for completely excised T1/T2 tumours with microscopic dermal PNI <0.1 mm only.

Rule

Clinical PNI is a different disease. Image it with MRI before any further surgery: the extent along the nerve decides the resection and the radiotherapy field.

Preoperative magnetic resonance imaging should be considered for patients with clinical evidence of perineural involvement.

Source: CCA keratinocyte cancer guideline v1.44, PP 11.5.2. NZSCD 20239 lists “Neurological symptoms (neuralgia or muscle weakness)” as a high-risk criterion.

Small-calibre dermal PNI<0.1 mm, dermis only, no symptomsLarge-calibre or deep PNI≥0.1 mm, or deeper than the dermis
Nodal metastasis (Carter 2013)ReferenceHR 5.6 (univariate)
BWH factorNoYes (calibre ≥0.1 mm)
Adjuvant radiotherapyNot indicated if completely excised (BAD; below CCA trigger)Surgery plus RT recommended (CCA EBR 11.7.2)
Report items requiredCalibre, depth, number of nervesCalibre, depth, number of nerves
Check
Which row changes the treatment plan?
□ Guess   □ Fairly sure   □ Certain
✓ (a) Correct. Calibre and depth move a tumour between no adjuvant treatment and surgery plus RT.
✗ (b) The same three items are required for every PNI report.
✗ (c) A risk estimate, not a decision; and calibre loses significance on multivariate analysis.
Worked case — 5 steps
Referral67-year-old man, upper back. Excision: invasive SCC, 40 mm, moderately differentiated, 4 mm thick, confined to dermis and fat, margins 4 mm clear. Report: “PNI present.” No LVI. No neurological symptoms.
  1. WorkupStop at “PNI present”: request calibre, depth and number. Calibre ≥0.1 mm would add a BWH factor and trigger the CCA radiotherapy recommendation.PP 11.5.1
  2. WorkupAddendum: two nerves, 0.3 mm, in the subcutis. Large calibre, deep, more than one.
  3. StagingBWH T2b (size, PNI); NCCN very high risk. 5-year nodal metastasis risk about 11%.
  4. TreatmentRecommend adjuvant radiotherapy to the primary site. CCA surgery plus RT for a nerve >0.1 mm; NCCN “large or named nerve involvement … consider: Adjuvant RT”.EBR 11.7.2
  5. StagingImage the draining basins; no MRI without symptoms. MRI is for clinical PNI.PP 11.5.2
What would change this? An addendum reading “one dermal nerve, 0.05 mm” makes this BWH T2a with no radiotherapy indication.

Why?

Why does nerve calibre lose significance on multivariate analysis, yet still guide radiotherapy?

Show answer
Large-calibre PNI occurs mostly in large, deep, poorly differentiated tumours, so much of its apparent effect on metastasis is shared with diameter and LVI. It still marks a route along which tumour can extend beyond the excised field, which is a local-control problem that radiotherapy addresses. The 0.1 mm threshold rests on limited evidence: only some of the studies cited by AJCC 8 found it independently significant.
Evidence and other guidelinesCCA ≠ BAD on PNI and RT

Calibre series. Carter 201314 (n = 114): large- vs small-calibre PNI, nodal metastasis HR 5.6 (1.1–27.9) and disease-specific death HR 4.5 (1.2–17.0) on univariate analysis; calibre dropped out on multivariate analysis, where diameter and LVI dominated. Ross 200915: disease-specific death 32% vs 0% (P = .003). Later work suggests that the number of nerves involved may discriminate better than calibre.

Four positions on the same report. CCA EBR 11.7.2: surgery plus RT for a nerve >0.1 mm, with no depth qualifier. NCCN: “If extensive perineural, large or involvement, or other poor prognostic features, consider: Adjuvant RT.” BAD: strong recommendation against RT for excised T1/T2 tumours with dermal PNI <0.1 mm only. NZSCD: “Consider adjuvant radiotherapy in addition to wide excision for Poorly Differentiated SCC or SCC with perineural invasion, especially in high risk locations.” A single 0.15 mm dermal nerve in a small trunk tumour triggers RT under CCA and not under NCCN.

Unknowns. No randomised trial of adjuvant RT for PNI exists. The UICC TNM9 PNI definition quoted in some summaries (“five or more nerves”) is unconfirmed and is not used here. The exact PNI criterion in the protocol (clinical or named-nerve PNI) is unverified.

TreatmentHow wide, and what if the margin is involved?

Basics: clinical margin, histological margin and margin control

The clinical margin is measured on the skin from the visible edge of the tumour before excision; guideline margins are clinical margins. The histological margin is measured by the pathologist on the processed specimen and is always smaller.

Standard excision with vertical (“bread-loaf”) sections examines a small sample of the margin. Mohs surgery and other forms of PDEMA examine the whole peripheral and deep margin en face, and remove further tissue only where tumour remains. Public Mohs surgery is provided at Te Toka Tumai Auckland; access from other regions varies, so check your region’s referral route. Staged excision with en face sections is an alternative.

Case
Excision, lower leg, 81-year-old man: 20 mm moderately differentiated cSCC, 3 mm thick. Deep margin involved; peripheral margins 2 mm. Immunocompetent. Nodes impalpable.
What should the MDM recommend for the margin?
□ Guess   □ Fairly sure   □ Certain
✗ (a) True of some BCCs, and CCA notes a positive margin does not imply persistence, but no guideline offers observation for an involved invasive cSCC margin.
✓ (b) Correct. CCA PP 10.2.1 and 12.3.4; NCCN “Re-resect, if feasible or RT”; EADO 2026 re-excision for operable cases.
✗ (c) Topical therapy does not treat invasive cSCC at a deep margin.
✗ (d) The margin is the problem; SLNB is not standard and does not address residual tumour.
An involved margin in invasive cSCC is treated, not watched. Re-excision comes first where operable; radiotherapy is the alternative when re-excision would be disfiguring, disabling or not feasible. The habit of observing some incompletely excised low-risk BCCs does not transfer: residual cSCC recurs, and recurrent cSCC is itself a high-risk tumour.

Rule

SourceLow riskHigh / very high risk
Brodland & Zitelli 19924 mmAt least 6 mm
NZSCD 2023No separate figure4–6 mm (its high-risk SCC margin); specialist advice where margins are uncertain, close or inadequate
EADO 20264–6 mm, postoperative margin assessment (reported in the 2026 update; full text not re-checked)6–10 mm, or micrographic surgery
BAD 20204 mm6 mm high; 10 mm very high
NCCN v2.2026Standard excisionNo number; Mohs or preferred for very high risk
CCANo mm figure“Wider surgical margin should be planned”

Plan 4–6 mm for low risk. For high-risk SCC, NZSCD 2023 recommends 4–6 mm margins, with specialist advice where margins are uncertain, close or inadequate and margin-controlled surgery considered for high-risk or complex head and neck tumours. Brodland & Zitelli, BAD and EADO use at least 6 mm for high-risk tumours (BAD 10 mm for very high risk), so 6 mm satisfies both. This read-through adopts at least 6 mm, or complete margin control, for trunk and limb tumours with BWH factors and records the departure from NZSCD.

Minimal margins of excision of 4 mm … for all but the high-risk tumors, in which at least a 6 mm margin is recommended.

Source: Brodland DG, Zitelli JA. J Am Acad Dermatol 1992;27:24116 (prospective Mohs series; high risk: ≥2 cm, grade ≥2, subcutaneous invasion, high-risk site). NZSCD 20239; EADO 2026 Part 2 Rec. 217 (extracted); NCCN Squamous Cell Skin Cancer v2.2026 (redraw); CCA keratinocyte cancer guideline v1.44, EBR 11.7.1, 11.7.3 (Grade C). No randomised trial of margins exists in cSCC.

Rule

An involved margin in invasive cSCC is re-excised where operable, or treated with radiotherapy where re-excision is disadvantageous or not feasible. It is not observed.

Incompletely excised cutaneous squamous cell carcinomas should be prophylactically re-excised or treated with radiotherapy.

Source: CCA keratinocyte cancer guideline v1.44, PP 10.2.1, PP 12.3.4; NCCN: “Re-resect, if feasible or RT”; EADO 2026: “In case of positive margins, a re-excision shall be done for operable cases.”

Worked case — 5 steps
Referral72-year-old woman, dorsal forearm. Incisional biopsy: invasive SCC, poorly differentiated. Clinical diameter 25 mm. Immunocompetent. Thin skin; on warfarin.
  1. StagingNCCN very high risk before excision; at least BWH T2b. Poor differentiation and ≥2 cm are two BWH factors.
  2. TreatmentMargin: at least 6 mm clinical, or complete margin control. Brodland high-risk features: ≥2 cm, grade ≥2. EADO: 6–10 mm or micrographic surgery. NZSCD 2023: 4–6 mm for high-risk SCC, with specialist advice on margins; 6 mm satisfies both.
  3. TreatmentStandard excision with postoperative margin assessment is acceptable where Mohs is not available. NCCN v2.2026 (redraw) accepts “wider surgical margins and postoperative margin assessment”.
  4. TreatmentRepair by linear closure, graft or secondary intention until margins are confirmed. NCCN lists these repairs after standard excision.
  5. WorkupAsk for thickness, depth, PNI detail and margins in mm on the excision report. The incisional biopsy cannot give thickness or level.
What would change this? A 12 mm well-differentiated tumour on the same forearm needs a 4–6 mm margin and no margin control.

Why?

Why does an involved cSCC margin not allow the observation sometimes accepted for BCC?

Show answer
cSCC metastasises; BCC almost never does. Residual cSCC that recurs locally becomes a recurrent tumour, which NCCN, NZSCD and CCA all class as high risk, with a greater chance of nodal spread and a harder second operation. A positive margin does not always mean residual tumour, but in invasive cSCC the cost of that bet falls on the nodes, not only on the scar.
Evidence and other guidelinesNZSCD 4–6 mm ≠ BAD 4/6/10 mm

Evidence base. One prospective Mohs series (Brodland & Zitelli 1992): “Four millimeter margins were adequate for most”; subclinical extension was greater with size ≥2 cm, grade ≥2 (moderately differentiated counts), subcutaneous invasion and high-risk site. No randomised trial of any margin or modality exists in cSCC. CCA gives no millimetre recommendation; its background text says a 4 mm margin is required for most well-differentiated cSCCs. EADO’s low-risk margin was 5 mm in 2023; the 2026 update reportedly gives 4–6 mm (full text not re-checked).

Mohs. CCA: “MMS and wide excision achieve similar cure rates for the management of cSCC of the face.” Pooled Mohs vs excision recurrence 3.0% vs 5.4%, not significant (Lansbury 201318). Mohs superiority in cSCC is extrapolated from BCC data. NCCN v2.2026 (redraw): “Mohs or other forms of PDEMA (preferred for very high risk)”; for tumours <6 mm without other high-risk features, other modalities if “at least 4-mm clinically tumor-free margins can be obtained”.

Close margins. BAD escalates at <1 mm histological clearance, with a lower threshold in the immunosuppressed. NCCN and CCA give no number.

StagingNodes: examine, image, or biopsy the sentinel node?

Basics: how nodal disease is looked for in cSCC

A trunk or limb cSCC drains to the axilla (and epitrochlear nodes for the forearm and hand), the groin (and popliteal nodes for the leg and foot), or, for trunk primaries near the midline, more than one basin. In-transit metastases are dermal or subcutaneous deposits between the primary and the basin.

Tests, in order of invasiveness: examination; ultrasound with FNA of an abnormal node; contrast CT of the nodal basin to count and locate nodes once one is positive; CT chest, abdomen and pelvis or PET-CT for distant disease. SLNB uses the melanoma technique but has not been shown to change survival in cSCC.

Case
66-year-old man. Excision of a 35 mm poorly differentiated cSCC of the lower back, 5 mm thick, confined to dermis and fat, margins clear. BWH T2b. Referral: “nodes not examined”.
What should happen next for the nodes?
□ Guess   □ Fairly sure   □ Certain
✗ (a) SLNB is not standard: NCCN “consider”, EADO not routine, CCA silent; no survival benefit shown.
✗ (b) CCA requires examination of the draining nodes in high-risk disease, and BWH T2b carries about an 11% 5-year risk of nodal metastasis.
✓ (c) Correct. Examination (CCA); imaging with a risk factor, ultrasound preferred for nodes (EADO 2026); NCCN MRI, CT and/or ultrasound for very high risk.
✗ (d) No guideline recommends elective dissection of a clinically and radiologically normal basin in cSCC.
Every high-risk cSCC needs its draining basins examined, and at two BWH factors the 5-year risk of nodal metastasis passes 10%, so imaging is reasonable. Ultrasound with FNA of anything abnormal is the nodal test EADO prefers (sensitivity 91%, specificity 78%). Elective dissection is not practised, and SLNB is an option to discuss, not a default.

Rule

Examine the draining basins in every high-risk, recurrent or locally advanced cSCC and at every follow-up visit. Image when a risk factor is present: EADO images only then and prefers ultrasound for nodes; NCCN offers MRI, CT and/or ultrasound for very-high-risk tumours; CCA says CT or PET-CT “may be appropriate” in larger tumours. An abnormal node is sampled by FNA or core, then staged with contrast CT of the basin and CT chest, abdomen and pelvis or PET-CT.

For recurrent and/or locally advanced cutaneous squamous cell carcinomas, the draining regional nodes must be examined (even after treatment of the primary site).

Source: CCA keratinocyte cancer guideline v1.44, PP 12.3.5; EADO 2026 Part 1 Rec. 519 (extracted; ultrasound sensitivity 91%, specificity 78%); NCCN Squamous Cell Skin Cancer v2.2026, very-high-risk and palpable-node pathways (redraw).

Rule

SLNB is not a standard in cSCC. NCCN says consider it for recurrent tumours or those with multiple high-risk features; EADO does not recommend it routinely; BAD confines it to trials or MDM discussion; CCA makes no recommendation. Positivity rises with stage, but no study shows that finding occult nodes earlier improves survival. Discuss it, record the reasoning, and do not let it delay treatment of the primary.

Source: NCCN v2.2026 (redraw): “Consider sentinel lymph node biopsy (SLNB) in cases that are recurrent or with multiple high-risk features”; EADO 2026 (recommendation wording not seen; reported unchanged from 2023); BAD 202013; Schmitt AR et al., JAMA Dermatol 2014;150:1920.

Worked case — 5 steps
Referral63-year-old man. Excised 38 mm poorly differentiated cSCC of the forearm, 6.5 mm thick (BWH T2b, NCCN very high risk). Ultrasound: one 18 mm axillary node with loss of the fatty hilum.
  1. WorkupUltrasound-guided FNA of the node. NCCN: FNA or core biopsy of an abnormal node.
  2. StagingFNA positive: contrast CT of the axilla for size, number and location of nodes. NCCN nodal-basin CT after a positive sample.
  3. StagingCT chest, abdomen and pelvis or PET-CT to exclude distant disease. NCCN “as clinically indicated”.
  4. TreatmentNo SLNB: nodal disease is already proven. SLNB stages a clinically and radiologically normal basin only.
  5. TreatmentMDM: therapeutic axillary dissection; adjuvant radiotherapy decided on the pathology. NCCN trunk and limb pathway; CCA PP 18.2.1.
What would change this? A negative FNA from a suspicious node is not an all-clear: NCCN advises re-evaluation by examination, CT, repeat FNA, core or excision biopsy.

Why?

Why does a higher sentinel node positivity rate in BWH T2b not by itself justify the procedure?

Show answer
Positivity measures the yield of a staging test, not the benefit of doing it. Benefit would need the positive result to lead to a treatment that improves outcome, and no study shows that dissecting or irradiating an occult cSCC node earlier improves survival. The T2b figure itself rests on 5 positives in 17 patients. In NZ the adjuvant systemic consequence of a positive node is unfunded.
Evidence and other guidelinesNCCN consider ≠ EADO not routine

SLNB yield. Schmitt 2014: overall positivity 12.3%, all positives in tumours >2 cm; BWH T2a 6/85 (7.1%), T2b 5/17 (29.4%), T3 3/6 (50%). A 2025 head and neck meta-analysis (Cancers, 38 studies)21: pooled occult nodal metastasis 13.9%; recurrence 8.3% after vs 16.9% with observation; mortality 6.1% vs 29.9%. The authors state these differences are “not assumed to be causative”: the comparison is uncontrolled and confounded by patient selection. EADO 2026 cites positivity from 7.1% (T2a) to 50% (T3) and states that evidence on overall survival is lacking.

Imaging modality. EADO prefers ultrasound for nodes; NCCN lists MRI, CT and/or ultrasound; CCA mentions CT or PET-CT for larger tumours; a recent US consensus prefers CT. EADO states that specific high-risk factors for nodal imaging “cannot be given” (2023 wording). All imaging recommendations are consensus-level.

NZSCD: “Consider the risk of regional metastasis and its management, such as sentinel node biopsy or CT staging.”

Check
A 66-year-old has a 35 mm poorly differentiated cSCC of the lower back (BWH T2b); basin ultrasound is normal. You had planned wide excision with clinical and ultrasound follow-up, without SLNB. You learn this is a recurrence at the site of an excision two years ago. Offering SLNB becomes:
much less appropriateunchangedmuch more appropriate
□ Guess   □ Fairly sure   □ Certain
Defensible range 0 to +1. NCCN names recurrence as a reason to consider SLNB; EADO does not recommend it routinely; BAD limits it to trials or MDM discussion; CCA is silent. No study shows a survival benefit.

TreatmentA positive node outside the head and neck

Basics: dissection, extranodal extension and adjuvant radiotherapy

A therapeutic dissection removes the nodal basin (axillary levels I–III; inguinal, with iliac nodes when involved), not just the palpable node. The pathology report gives the number of nodes involved, the largest deposit and whether there is ENE (extranodal extension, also called ECE).

PORT (postoperative radiotherapy) is delivered to the dissected basin, the primary site, or both. In TROG 05.0122 the head and neck regimen was 60–66 Gy. CCA advises starting within 6 weeks of surgery.

Case
70-year-old man. cSCC of the shin excised 8 months ago. Now a 25 mm right inguinal node, FNA positive. CT: single inguinal node; no pelvic or distant disease. ECOG 1. Immunocompetent.
What is the standard treatment of the groin?
□ Guess   □ Fairly sure   □ Certain
✗ (a) Leaves the rest of the basin untreated; therapeutic dissection is the standard (EADO Grade A).
✗ (b) Radiotherapy alone is for patients who cannot have surgery.
✓ (c) Correct. NCCN trunk and limb pathway: regional dissection, then “Consider RT, especially if multiple involved nodes or extranodal extension”; CCA PP 18.2.1: surgery and adjuvant RT.
✗ (d) Resectable single-node disease is treated surgically; systemic therapy is for disease not curable by surgery or RT, and cemiplimab is unfunded.
Resectable nodal cSCC outside the head and neck is treated by therapeutic dissection of the basin. What follows is where the guidelines split: CCA recommends radiotherapy for every axillary, epitrochlear or inguinal recurrence; NCCN makes it a consideration weighted by node number and extranodal extension.

Rule

Resectable nodal disease from a trunk or limb cSCC is treated by therapeutic dissection of the basin, with the primary site excised if disease remains. Extensive nodal disease is discussed at the MDM before surgery. After dissection the radiotherapy recommendation depends on the guideline: CCA recommends it for every axillary, epitrochlear or inguinal recurrence; NCCN says consider it, especially with multiple nodes or .

Recurrences of cutaneous squamous cell carcinoma in the axillary, epitrochlear or inguinal lymph nodes should be treated with surgery and adjuvant radiotherapy.

Source: CCA keratinocyte cancer guideline v1.44, PP 18.2.1, PP 12.4.1; NCCN Squamous Cell Skin Cancer v2.2026 (redraw): trunk and extremities → “Excision of primary tumor and regional lymph node dissection” → “Consider RT, especially if multiple involved nodes or extranodal extension (ENE) is present”; EADO 2026: “Therapeutic radical regional lymph node dissection remains the standard of care” (Grade A).

Rule

PORT to the primary site is considered for T3/T4 tumours, invasion beyond fat or into bone, depth >6 mm, rapid growth, recurrence, inadequate margins where further surgery is problematic, poor , , LVI, and in-transit or nodal disease. Start within 6 weeks. Do not add carboplatin. No randomised trial compares adjuvant radiotherapy with observation in cSCC.

Do not routinely offer carboplatin chemotherapy in addition to adjuvant radiotherapy for patients who have undergone excision of high-risk head and neck cutaneous squamous cell carcinoma.

Source: CCA keratinocyte cancer guideline v1.44, PP 12.3.3, PP 12.1.1, EBR 18.2.1 (Grade D), EBR 18.2.5 (Grade B; from TROG 05.01, head and neck only).

Worked case — 5 steps
Referral61-year-old woman. cSCC of the upper arm excised 10 months ago. Axillary dissection for a palpable node: 2 of 14 nodes involved, largest 22 mm, ENE present. Margins clear. ECOG 0. Immunocompetent.
  1. StagingMultiple nodes with ENE. The highest-risk nodal pattern in both guidelines.
  2. TreatmentAdjuvant radiotherapy to the axilla. CCA and NCCN (“especially if multiple involved nodes or ENE”) agree here.PP 18.2.1
  3. TreatmentRadiotherapy alone, without concurrent carboplatin. TROG 05.01: no benefit from weekly carboplatin (head and neck; extrapolated).EBR 18.2.5
  4. FundingMeets the C-POST nodal definition: ENE with a node ≥20 mm. Adjuvant cemiplimab is NCCN category 1, and EADO 2026 leaves the decision to the multidisciplinary tumour board; it is not funded in NZ.
  5. Follow-upNZSCD regional-disease schedule: 3-monthly in year 1, 4-monthly in year 2, 6-monthly to year 5, then annually. CCA: 3-monthly for 2 years after resected nodal disease.PP 18.2.2
What would change this? One node without ENE: CCA still recommends radiotherapy, NCCN leaves it as a consideration, and C-POST eligibility is lost.

Why?

Why can TROG 05.01 not be cited as evidence that adjuvant radiotherapy works?

Show answer
Every patient in TROG 05.01 received radiotherapy; the trial randomised the addition of weekly carboplatin and found none (5-year freedom from locoregional relapse 83% vs 87%, HR 0.84). It had no untreated arm, so it says nothing about radiotherapy versus observation. It enrolled head and neck cSCC only, so its application to axillary or groin disease is extrapolation.
Evidence and other guidelinesCCA ≠ NCCN on RT after nodal dissection

TROG 05.01 (Porceddu 201822, n = 321, head and neck cSCC after resection of gross disease, NZ co-investigators): all received 60–66 Gy ± weekly carboplatin; 77% had high-risk nodal disease; 5-year freedom from locoregional relapse 83% vs 87%, HR 0.84 (0.46–1.55), P = .58; no difference in disease-free or overall survival; isolated distant first failure 7% in both arms.

After axillary or groin dissection. CCA PP 18.2.1: surgery and adjuvant RT for all. NCCN: “Consider RT, especially if multiple involved nodes or ENE.” EADO 2026 recommends adjuvant RT after dissection for head and neck cSCC (possible exception: single node <3 cm without ECE in an immunocompetent patient) and is not specific for trunk and limb. The single node without ENE is where the MDM must choose.

Primary site. EADO 2026 Rec. 6 (Grade C): adjuvant RT “may be considered for selected patients with risk features, such as perineural invasion, deep tissue or bone infiltration, poor differentiation, tumor size ≥ 2 cm, or recurrence”; Rec. 8: with ≥2 factors adjuvant RT may lower locoregional recurrence, with no effect on disease-specific death. CCA EBR 18.2.1 is Grade D. The observational base is small non-randomised series.

In-transit disease. CCA PP 11.9.1: “Dermal lymphatic spread (in-transit metastasis) should be managed by wide surgical excision followed by adjuvant radiotherapy.”

FundingSystemic therapy: what exists, and what is funded here

FundingPosition as at the October 2026 Pharmac Schedule, checked 1 October 2026. Funding and Special Authority criteria change often: check the current Schedule before acting on them.

Basics: advanced, locally advanced and extremely-high-risk cSCC

laCSCC (NCCN): primary or recurrent extensive disease where surgery or radiotherapy may not cure, or would cause significant functional impairment. EADO’s DTT-CSCC groups 3–5 are locally advanced, locoregionally metastatic and distantly metastatic disease.

Neoadjuvant therapy is given before surgery and judged on the resected specimen (pCR: no viable tumour; MPR: 10% or less). Adjuvant therapy follows surgery and radiotherapy. “Extremely high risk” is the NCCN label for the population studied in .

Medsafe registration and Pharmac funding are separate: a registered medicine can be prescribed, but without a or listing the patient pays.

Case
66-year-old man. Axillary dissection for nodal cSCC from the forearm: 3 of 12 nodes, largest 24 mm, ENE present. Adjuvant radiotherapy completed 4 weeks ago. ECOG 0. No autoimmune disease; not immunosuppressed. He asks about “the immunotherapy after radiotherapy”.
What systemic therapy can be offered through the public system?
□ Guess   □ Fairly sure   □ Certain
✓ (a) Correct. C-POST-eligible (ENE with a node ≥20 mm; ≥3 nodes). NCCN category 1; EADO 2026 leaves the decision to the multidisciplinary tumour board; unregistered for this use and unfunded in NZ; no recruiting NZ trial.
✗ (b) Carboplatin added nothing in TROG 05.01, and radiotherapy is complete.
✗ (c) SA2631’s only SCC indication is head and neck SCC “of mucosal origin”; and adjuvant pembrolizumab (KEYNOTE-630) was negative.
✗ (d) FDA approval confers neither Medsafe registration nor Pharmac funding. The adjuvant indication has neither.
This patient meets the C-POST nodal definition twice (ENE with a node ≥20 mm; three involved nodes). Adjuvant cemiplimab is an international standard for him and is not available publicly in NZ: not in the Medsafe datasheet for adjuvant use, not funded, and no NZ trial is recruiting. The MDM records the recommendation, the funding gap and the options: self-funding, a trial overseas, or observation.

Rule

After surgery and radiotherapy, “extremely high risk” is the C-POST population: ENE with the largest node ≥20 mm, or ≥3 involved nodes; or in-transit metastases, T4 (bone invasion), perineural invasion, or local recurrence with at least one further risk feature. Here adjuvant cemiplimab is an international standard (NCCN category 1 preferred; EADO 2026: the decision “should be discussed in the multidisciplinary tumor board”). In NZ it is not Medsafe-approved for adjuvant use and not funded. Adjuvant pembrolizumab was negative (KEYNOTE-630).

… at high risk for recurrence owing to nodal features (extracapsular extension with largest node ≥20 mm in diameter or at least three involved nodes) or nonnodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with ≥1 additional risk feature).

Source: Rischin D et al., N Engl J Med 2025;393:7741 (C-POST, NCT0396900423), abstract; NCCN v1.2026 onward (secondary reports); EADO 2026 Part 217, abstract (full recommendation wording and grade not verified; full text paywalled); Medsafe Libtayo datasheet (revised 2 October 2025)24; Pharmac Schedule October 202625.

Rule

Advanced cSCC not curable by surgery or radiotherapy is treated first-line with anti-PD-1. Cemiplimab is Medsafe-registered for it and not funded; application P-001628 is on the November 2026 agenda. Pembrolizumab is not funded for any cutaneous SCC. Neoadjuvant cemiplimab before a disfiguring or disabling resection is an NCCN “consider”, off-label everywhere and unfunded here. The action available in NZ is the MDM referral before the operation is booked.

Cemiplimab (branded as Libtayo) for skin cancer — The Committee will discuss an application for cemiplimab for the treatment of people living with squamous cell carcinoma. This application is for first line treatment, for people whose cancer is advanced or has spread and cannot be removed with surgery or radiation therapy.

Source: Pharmac, Agenda for November 2026 CTAC meeting (published 11 September 2026)26; SA2631 (October 2026)27: SCC criterion limited to head and neck SCC “of mucosal origin”; CCA keratinocyte cancer guideline v1.44, PP 18.2.4; NCCN v2.2026 neoadjuvant criteria (redraw). See the funding table.

Worked case — 5 steps
Referral74-year-old man. 8 cm recurrent cSCC of the dorsum of the dominant right hand, invading extensor tendons; epitrochlear and axillary nodes clinically normal. Plastic surgery has booked a below-elbow amputation in 2 weeks. Not discussed at an MDM. ECOG 1. Not immunosuppressed.
  1. TreatmentHold the booking for an MDM discussion. Losing the dominant hand is the “significant functional impairment” in the NCCN laCSCC definition.
  2. StagingStage first: MRI of the hand and forearm, nodal ultrasound, CT chest. NCCN very-high-risk planning: MRI, CT and/or ultrasound.
  3. TreatmentOptions for the patient: amputation; neoadjuvant cemiplimab then reassessment; definitive radiotherapy ± systemic therapy. NCCN: consider neoadjuvant cemiplimab where surgery “may result in significant functional limitation”.
  4. FundingCemiplimab: registered for laCSCC unsuitable for curative surgery or RT; not funded; no NZ trial recruiting. Neoadjuvant use is off-label and would be self-funded.
  5. Follow-upIf neoadjuvant therapy is given, judge it on the resected specimen. Gross 2022: pCR 51% with a radiological response rate of 68%; the pathological endpoint is what predicts outcome.
What would change this? A tumour resectable with a functional reconstruction goes straight to surgery; the neoadjuvant question arises only where surgery alone may not cure or would cost function.

Why?

Why is a slow or partial early response to cemiplimab in advanced cSCC not treated as failure?

Show answer
Responses to PD-1 blockade in cSCC deepen over months: in the pooled EMPOWER-CSCC-1 analysis (Rischin 2021) the median time to complete response was 11.2 months, and 88% of responders remained in response at 12 months. Judging the drug on the first restaging scan, as one would a cytotoxic, stops treatment before the response it can produce has had time to appear.
Evidence and other guidelinesNCCN/EADO standard; unfunded here

C-POST (n = 415; cemiplimab 350 mg 3-weekly for 12 weeks, then 700 mg 6-weekly to 48 weeks): disease-free survival HR 0.32 (0.20–0.51); 24-month DFS 87.1% vs 64.1%; locoregional recurrence HR 0.20, distant HR 0.35. Overall survival immature (2-year 94.8% vs 92.3%, secondary source). Grade ≥3 adverse events 23.9% vs 14.2%; discontinuation 9.8% vs 1.5%. NZ sites: Auckland and Palmerston North (closed). Excluded ECOG ≥2 and significant autoimmune disease; exclusion of transplant recipients is inferred, not seen. Eligibility was not restricted to the head and neck; its application to axillary and groin disease rests on that eligibility wording.

KEYNOTE-6302 (adjuvant pembrolizumab, n = 450, broader risk criteria): RFS HR 0.76, P = 0.072; OS HR 1.47 (0.87–2.48); stopped for futility. A pooled reconstruction of both trials is hypothesis-generating only.

Neoadjuvant cemiplimab (Gross 202228, n = 79, up to 4 doses): 51% (39–62), 13%, radiological response 68%, grade ≥3 AEs 18%. Gross 202329: 12-month event-free survival 89%; none of 40 patients with pCR had recurred at a median 18.7 months. 91% head and neck; single-arm. EADO: a “promising off-label alternative”.

Advanced disease. EMPOWER-CSCC-1 long-term30: ORR 47.2%, median PFS 26.0 months. Rischin 202131 (pooled groups 1–3, n = 193, median follow-up 15.7 months): median time to complete response 11.2 months; 87.8% of responders still in response at 12 months. KEYNOTE-62932: ORR 50.0% locally advanced, 35.2% recurrent or metastatic. CCA EBR 12.3.1 (Grade B): curative-dose radiotherapy is an alternative when surgery is declined or inappropriate. EADO lists cetuximab combinations second line; the NZ cetuximab Special Authority is written for locally advanced head and neck SCC with radiotherapy and has not been tested for cutaneous primaries.

Follow-upAfter treatment: how often, and who needs more?

Basics: what a follow-up visit contains, and the precursor lesions

Each visit: the scar, the in-transit path between the primary and the basin, the draining nodes, and a full skin examination; patients are taught self-examination. After any keratinocyte cancer, annual skin examination is the minimum for life.

Immunosuppression that matters most: solid organ transplant (especially kidney and heart), CLL and HIV. Actinic keratosis is a keratotic sun-damage lesion with a low per-lesion risk of invasion. Bowen’s disease is SCC in situ. A keratoacanthoma is a rapidly growing crateriform tumour that cannot be reliably separated from well-differentiated cSCC.

Case
58-year-old man, renal transplant 14 years ago, on tacrolimus, mycophenolate and prednisone. Third invasive cSCC this year, all on trunk and limbs, all excised with clear margins. He has started nicotinamide 500 mg twice daily on a friend’s advice.
Which prevention step does the evidence support?
□ Guess   □ Fairly sure   □ Certain
✗ (a) ONTRAC enrolled immunocompetent patients. ONTRANS, in transplant recipients, found no reduction (rate ratio 1.0).
✓ (b) Correct. CCA PP 16.3.1 (acitretin for multiple KCs; funded under SA2024) and PP 16.3.2 (reduce immunosuppression); TUMORAPA: new cSCC 22% vs 39% with sirolimus.
✗ (c) He is developing several tumours a year; CCA recommends chemoprophylaxis and a review of immunosuppression for multiple KCs.
✗ (d) Immunosuppression is adjusted by the transplant team, not stopped; graft loss is the cost.
Nicotinamide reduced keratinocyte cancers in immunocompetent patients (ONTRAC) and did not in transplant recipients (ONTRANS, stopped early, n = 158). The interventions with evidence in this group are acitretin and a change of immunosuppression, particularly an mTOR switch, whose benefit is greatest after the first cSCC. Both belong to a joint decision with the transplant physician.

Rule

In an organ transplant recipient with multiple cSCC, offer acitretin (funded, SA2024; teratogenic) and ask the transplant team to review immunosuppression, including an mTOR switch, whose benefit is greatest after the first cSCC. Do not use nicotinamide for prevention in transplant recipients. Their excess risk is mostly multiplicity: many more tumours, with a higher metastasis rate and a much higher rate of death from cSCC.

Chemoprophylaxis with systemic acitretin should be considered for reducing tumour burden in patients who develop multiple keratinocyte cancers.

Source: CCA keratinocyte cancer guideline v1.44, PP 16.3.1, PP 16.3.2; Euvrard S et al., NEJM 2012;367:32933 (TUMORAPA); Allen NC et al., NEJM 2023;388:80434 (ONTRANS); Chen AC et al., NEJM 2015;373:161835 (ONTRAC); Mackenzie KA et al., Nephrol Dial Transplant 2010;25:30036 (Christchurch); Gjersvik P et al., JAMA Dermatol 2023;159:92337 (Norway).

Rule

NZSCD 2023 groupSchedule
Low-risk cSCC6–12-monthly for 5 years, then at least annually for life
High-risk cSCC3–6-monthly for 2 years, 6-monthly for 3 years, then annually for life
Regional (nodal) disease3-monthly in year 1, 4-monthly in year 2, 6-monthly for 3 years, then annually for life

70–80% of recurrences occur within 2 years. Every visit examines the scar, the in-transit path, the draining nodes and the whole skin.

For patients with cutaneous squamous cell carcinoma that is moderately to poorly differentiated or occurs on the lip or ear, initial follow-up should be conducted at 3 months and then every 6 months. It should always include examination of the draining lymph node basin.

Source: NZSCD SCC and BCC Guidelines, Follow-Up Recommendations (May 2023)38; CCA keratinocyte cancer guideline v1.44, PP 19.1.2, PP 18.2.2; CCA quick reference guide39: annual skin examination as a minimum after any keratinocyte cancer.

Rule

At follow-up, biopsy the outlier: the “actinic keratosis” that persists after cryotherapy, enlarges or becomes tender. Excise a lesion that looks like a early rather than waiting for it to resolve.

If a skin lesion is initially considered to be an actinic keratosis, but it persists following cryotherapy, enlarges or becomes tender, it should be biopsied.

Source: CCA keratinocyte cancer guideline v1.44, PP 8.2.1; PP 8.2.2: “Keratoacanthomas should be managed by early excision rather than relying on correct clinical diagnosis and waiting for spontaneous resolution.”

Worked case — 5 steps
Referral69-year-old woman, immunocompetent. Excised 28 mm poorly differentiated cSCC of the forearm (BWH T2b), margins clear; axillary ultrasound normal; no adjuvant radiotherapy. Many actinic keratoses on both forearms.
  1. Follow-upFirst review at 3 months. CCA: poorly differentiated cSCC.PP 19.1.2
  2. Follow-upNZSCD high-risk schedule: 3–6-monthly for 2 years, 6-monthly for 3 years, then annually for life. 70–80% of recurrences occur in the first 2 years.
  3. Follow-upEach visit: scar, in-transit path, epitrochlear and axillary nodes, full skin check. CCA: always examine the draining basin.
  4. TreatmentField therapy for the actinic keratoses; biopsy any that persist, enlarge or become tender. 5-FU and imiquimod creams are funded without Special Authority.PP 8.2.1
  5. Follow-upAfter year 5: annual skin check for life, GP-led, with a written plan. NZSCD: annually for life.
What would change this? A renal transplant recipient with the same tumour would add acitretin and a review of immunosuppression; BAD would set 4-monthly review for 2 years, then 6-monthly.

Why?

Why is a transplant recipient more likely to die of cSCC?

Show answer
They develop far more tumours, and their rates of metastasis and of death from cSCC are also higher. In the Christchurch series, recipients who developed a keratinocyte cancer went on to 1.67 new tumours a year, with a median 2.2 years to the second, and each tumour is another chance of metastasis. In the Norwegian cohort (Gjersvik 2023) the rate of a second cSCC was 250.6 vs 30.9 per 1000 person-years (4.3-fold after adjustment), and after adjustment the metastasis rate was 1.5-fold and the rate of death from cSCC 5.5-fold higher in transplant recipients. Prevention targets the multiplicity.
Evidence and other guidelinesNo NZ transplant surveillance guideline

NZ data. Mackenzie 2010 (Christchurch, 384 renal transplant recipients, 1972–2007): 96 developed a non-melanoma skin cancer; 14 died of metastatic SCC (15% case fatality among those with NMSC); median time to a second NMSC 2.2 years; 1.67 new NMSC a year. A Norwegian cohort (Gjersvik 202337; 1,208 transplant recipients and 46,784 others with cSCC) reported a second cSCC at 250.6 vs 30.9 per 1000 person-years and a 5-year cumulative incidence of 55.0% vs 16.2% (full text, Table 3); after adjustment, transplant recipients had 1.5-fold the rate of metastasis and 5.5-fold the rate of death from cSCC. No NZ national transplant skin surveillance guideline exists. CCA: specialist review “at least annually”; BAD: 4-monthly for 2 years then 6-monthly, and a lower threshold for further treatment of a clear margin under 1 mm.

Prevention. TUMORAPA: new cSCC 22% (sirolimus) vs 39%, RR 0.56 (0.32–0.98); 23% stopped sirolimus for adverse events. CCA: “Prophylactic use of MTOR inhibitors does not seem warranted.” ONTRAC (immunocompetent, ≥2 NMSC in 5 years): NMSC −23% (4–38), SCC −30%, no benefit after stopping. : stopped early for poor recruitment (n = 158); rate ratio 1.0 (0.8–1.3), P = 0.96, so a small benefit is not excluded. CCA reserves nicotinamide for high-risk immunocompetent patients.

Checkpoint inhibitors after transplant. IPD meta-analysis (JAMA Oncol 2025, 343 recipients)40: acute rejection 36.2% at 1 year, graft loss 18.4%, cSCC ORR 61%; steroid plus mTOR-inhibitor maintenance associated with less rejection (HR 0.30). Hanna 202441: 12 kidney recipients switched to an mTOR inhibitor with pulsed prednisone, then cemiplimab: no rejection, ORR 5/11, one death from angioedema attributed to the mTOR cross-taper. Carroll 202242 (Australia): 17 kidney recipients, nivolumab on unchanged immunosuppression, no irretrievable rejection. The evidence is small and largely case-series.

CLL: keratinocyte cancer risk 5–8-fold, mostly cSCC; leukaemic infiltrates can obscure margins, especially on frozen section. Precursors. Actinic keratosis progression 0–0.075% per lesion-year, and “no reliable estimates” exist (Werner 201343); 0.60% at 1 year and 2.57% at 4 years in Criscione 200944, where about 65% of SCCs arose in lesions previously called AK; 40% of SCCs arose on skin clinically normal 12 months earlier. : 5-FU cure 87–92% (CCA); 12-month sustained clearance 69% in an RCT (Morton 200645); the “3–5% progression” figure is a background assertion. No metastatic rate for keratoacanthoma exists.

FundingNZ funding position at October 2026 Schedule (verified 1 October 2026)

FundingPosition as at the October 2026 Pharmac Schedule, checked 1 October 2026. Funding and Special Authority criteria change often: check the current Schedule before acting on them.

The single reference for every funding statement in this document. No systemic therapy for cutaneous SCC is publicly funded in New Zealand.

SettingAgentFunded?Conditions
Advanced cSCC (la/mCSCC), first lineCemiplimabNoMedsafe provisional consent for la/mCSCC not suitable for curative surgery or radiotherapy. Not on the Schedule or HML. Application P-001628 on the November 2026 CTAC agenda; no recommendation yet.
High-risk resected cSCC, adjuvant (after surgery and RT)CemiplimabNoAdjuvant indication not in the Medsafe datasheet; not funded; no application for this indication found. FDA-approved October 2025.
Before surgery, neoadjuvantCemiplimabNoOff-label everywhere; not registered or funded for this use.
Any cutaneous SCCPembrolizumabNoSA2631’s only SCC indication is recurrent or metastatic head and neck SCC “of mucosal origin”. KEYNOTE-630 (adjuvant) negative.
Locally advanced head and neck SCC with RTCetuximabDo not relySA2401 reads “squamous cell cancer of the head and neck”, not specified mucosal; applicability to cutaneous primaries is untested. Not an option for trunk or limb cSCC.
Actinic keratosis, Bowen’s disease, field treatmentImiquimod 5% cream; fluorouracil 5% creamYesFully subsidised; no Special Authority.
Photodynamic therapyMethyl aminolevulinate 16% creamHospital onlyHML, restricted (RS1127): dermatologist or plastic surgeon, or per an endorsed Health NZ protocol.
Chemoprevention, multiple keratinocyte cancersAcitretinYesSpecial Authority SA2024 (dermatologist, GP or nurse practitioner; pregnancy exclusion and counselling).
ChemopreventionNicotinamideNoOver-the-counter purchase. Not effective in transplant recipients (ONTRANS).
Radiotherapy (definitive, adjuvant, palliative)—YesPublic radiation oncology.
Mohs surgery—Auckland onlyPublic service at Te Toka Tumai Auckland; access from other regions varies; check your region’s referral route.
Clinical trials—None in NZNo recruiting cSCC trial lists a NZ site (ClinicalTrials.gov, 24 September 2026; ANZCTR not searched). Australian sites exist for neoadjuvant trials.

Sources: Pharmac Pharmaceutical Schedule October 202625 and Schedule Online (October 2026 edition)25; SA2631 form (October 2026)27; SA240146; SA202447; HML RS112748; Pharmac, Agenda for November 2026 CTAC meeting (11 September 2026)26; Medsafe Libtayo datasheet (revised 2 October 2025)24.

MDM listEight referrals, in the order they arrive

Each step reveals the next. The final step asks for the two-sentence directive.

Case 1 · Upper back, “PNI present”

Referral67-year-old woman. Excision, upper back: invasive SCC, 34 mm, moderately differentiated, 4 mm, confined to dermis and fat, margins clear (5 mm). “PNI present”: calibre, depth and number not stated. No LVI. Immunocompetent. No neurological symptoms.
Step 1
What BWH T stage can be assigned on the information given?
□ Guess   □ Fairly sure   □ Certain
✗ (a) BWH counts PNI only in a nerve ≥0.1 mm; calibre is unknown.
✗ (b) PNI ≥0.1 mm is one of the four BWH factors, and size already gives one factor.
✓ (c) Correct. Size ≥2 cm is one factor; PNI counts in BWH only at a calibre of 0.1 mm or more.

Case 2 · Ear cSCC addressed to this MDM

Referral79-year-old man. Excision, helix of left ear: invasive SCC, 22 mm, poorly differentiated, PNI in a 0.2 mm nerve, deep margin 0.5 mm. GP referral addressed to the Melanoma & HRSC MDM. Palpable 15 mm left parotid node.
Step 1
Where should this case be discussed?
□ Guess   □ Fairly sure   □ Certain
✗ (a) Nodal disease needs sampling, staging and MDM discussion before surgery.
✗ (b) Under the stated terms of reference, head and neck cSCC, including the ear, goes to the Head and Neck MDM.
✓ (c) Correct. Under the stated terms of reference, head and neck cSCC with a parotid node belongs to the Head and Neck MDM.

Case 3 · Forearm cSCC, amputation listed

Referral71-year-old woman. 9 cm recurrent cSCC of the dominant forearm, invading the radius on CT. Axilla clinically normal. Plastic surgery has listed a transhumeral amputation in 10 days; no MDM discussion. ECOG 1. No autoimmune disease; not immunosuppressed.
Step 1
What should happen first?
□ Guess   □ Fairly sure   □ Certain
✗ (a) Resectable is not the only question: amputation of the dominant arm is the functional loss that defines laCSCC and opens other options.
✓ (b) Correct. NCCN: multidisciplinary consultation for very-high-risk and locally advanced disease; staging decides the options.
✗ (c) This may be a curable tumour; the options must be laid out first.

Case 4 · Small arm cSCC, excised

Referral55-year-old man. Excision, upper arm: invasive SCC, 11 mm, well differentiated, 1.2 mm thick, dermis only, no PNI, no LVI, margins 4 mm peripheral and 3 mm deep. Immunocompetent. First skin cancer. GP asks for MDM discussion.
Step 1
Does this case need an MDM discussion?
□ Guess   □ Fairly sure   □ Certain
✗ (a) BWH T1: nodal risk is low and SLNB is not discussed.
✓ (b) Correct. BWH T1, NCCN low risk, clear margins: Te Aho excludes simple SCC from MDMs.
✗ (c) This MDM’s terms of reference are read with the national exclusion of simple SCC.

Case 5 · Shave biopsy, base transected

Referral76-year-old woman. Shave biopsy of a 22 mm nodule on the thigh: “invasive SCC, moderately differentiated, at least 1.8 mm, base transected; PNI not seen in the sample”. Nodes impalpable. Immunocompetent.
Step 1
What can be stated about the stage?
□ Guess   □ Fairly sure   □ Certain
✓ (a) Correct. Size gives one factor; thickness, level and PNI need the whole tumour.
✗ (b) “At least 1.8 mm” with a transected base is a floor, not a measurement.
✗ (c) The thickness is unknown, and a 22 mm limb tumour is already NCCN high risk.

Case 6 · BWH T2b, nodes normal: sentinel node?

Referral62-year-old man. Excision, lower back: invasive SCC, 31 mm, poorly differentiated, 5 mm, confined to fat, no PNI, margins clear. Ultrasound of both groins and axillae normal. Fit. He asks, “Has it spread to the glands?”
Step 1
What are the BWH T stage and the estimated 5-year risk of nodal metastasis?
□ Guess   □ Fairly sure   □ Certain
✗ (a) T3 needs four factors or bone invasion.
✗ (b) Two factors are present: ≥2 cm and poor differentiation.
✓ (c) Correct. Two factors.

Case 7 · Axillary nodes with ENE, radiotherapy done

Referral57-year-old man. cSCC of the forearm excised 14 months ago. Axillary dissection: 4 of 18 nodes, largest 31 mm, ENE present; adjuvant radiotherapy to the axilla completed 3 weeks ago. PET-CT after radiotherapy: no distant disease. ECOG 0. No autoimmune disease; not immunosuppressed.
Step 1
Does he meet the C-POST definition of extremely high risk?
□ Guess   □ Fairly sure   □ Certain
✗ (a) C-POST enrolled patients after surgery and radiotherapy.
✓ (b) Correct. He meets both nodal criteria.
✗ (c) C-POST enrolled local or regional cSCC; eligibility was not limited to the head and neck.

Case 8 · Unresectable leg and groin disease

Referral80-year-old woman. cSCC of the shin treated with surgery and radiotherapy 2 years ago. Now multiple unresectable in-transit deposits on the leg, a 4 cm inguinal mass fixed to the femoral vessels, and two lung nodules on CT. ECOG 1. No autoimmune disease; not immunosuppressed.
Step 1
What first-line treatment does the evidence support?
□ Guess   □ Fairly sure   □ Certain
✓ (a) Correct. EMPOWER-CSCC-1: ORR 47.2%, median PFS 26.0 months.
✗ (b) Lung disease makes this incurable by surgery.
✗ (c) Anti-PD-1 is first line for advanced cSCC (EADO 2026; CCA PP 18.2.4).

NumbersThresholds that change a decision

Number
In the largest prospective series, no cSCC of ___ mm thickness or less metastasised
mm
□ Guess   □ Fairly sure   □ Certain
2.0 mm (Brantsch 2008). Below it, NCCN low risk on depth; above it, high risk.
Number
NCCN makes thickness of more than ___ mm a very-high-risk feature on its own
mm
□ Guess   □ Fairly sure   □ Certain
6 mm (or invasion beyond fat). Very high risk opens margin control and nodal imaging.
Number
PNI counts as a BWH factor when the involved nerve is at least ___ mm in calibre
mm
□ Guess   □ Fairly sure   □ Certain
0.1 mm. Also the CCA trigger for surgery plus radiotherapy (EBR 11.7.2).
Number
Diameter of at least ___ cm is a BWH factor
cm
□ Guess   □ Fairly sure   □ Certain
2 cm. Also the NCCN trunk and limb low-risk ceiling and a CCA referral trigger.
Number
A cSCC larger than ___ cm is NCCN very high risk at any site
cm
□ Guess   □ Fairly sure   □ Certain
4 cm. Very high risk opens margin control and nodal imaging.
Number
BWH T2b begins at ___ factors
factors
□ Guess   □ Fairly sure   □ Certain
Two. 5-year nodal metastasis risk about 11%, the first count above 10%, so the basin is imaged.
Number
Brodland and Zitelli: a margin of ___ mm cleared most low-risk cSCC
mm
□ Guess   □ Fairly sure   □ Certain
4 mm (Brodland & Zitelli). NZSCD 2023 recommends 4–6 mm for high-risk SCC; EADO 2026 reportedly 4–6 mm for low risk.
Number
For high-risk cSCC, Brodland and Zitelli recommend a margin of at least ___ mm
mm
□ Guess   □ Fairly sure   □ Certain
6 mm, or complete margin control (Mohs/PDEMA).
Number
BAD lowers the threshold for further treatment in immunosuppressed patients when histological clearance is under ___ mm
mm
□ Guess   □ Fairly sure   □ Certain
1 mm (BAD 2020, from secondary summaries). Other guidelines give no number.
Number
C-POST nodal risk: ENE with the largest node at least ___ mm
mm
□ Guess   □ Fairly sure   □ Certain
20 mm, with ENE. Defines the adjuvant cemiplimab population (unfunded in NZ).
Number
CCA: first follow-up for moderately or poorly differentiated cSCC at ___ months
months
□ Guess   □ Fairly sure   □ Certain
3 months, then 6-monthly, always with nodal examination (PP 19.1.2).
Number
70–80% of cSCC recurrences occur within ___ years
years
□ Guess   □ Fairly sure   □ Certain
2 years (NZSCD). The follow-up intensity follows this curve.

Your answersCounts only

Answer key

GlossaryTerms used in this document

AJCC 8
AJCC 8th edition cSCC staging, printed in the head and neck section. Its T categories apply to head and neck primaries only.
BWH
Brigham and Women’s Hospital T staging for cSCC. Counts four factors: ≥2 cm, poor differentiation, PNI ≥0.1 mm, invasion beyond fat. Validated at all body sites.
Bowen’s disease
Squamous cell carcinoma in situ of the skin. Treated by excision, 5-FU cream, cryotherapy or photodynamic therapy.
C-POST
Phase 3 trial of adjuvant cemiplimab versus placebo after surgery and radiotherapy in high-risk cSCC (NEJM 2025). Disease-free survival HR 0.32.
CTAC
Pharmac’s Cancer Treatments Advisory Committee, which reviews funding applications and makes recommendations.
DTT-CSCC
EADO “difficult-to-treat” cSCC, groups 1–5: complex common tumours (1–2), locally advanced (3), locoregional (4) and distant (5) metastatic disease.
ENE
Extranodal extension (also ECE, extracapsular extension): tumour through the lymph node capsule. Drives adjuvant radiotherapy and the C-POST risk definition.
HML
Hospital Medicines List (Schedule Section H): medicines funded for use in Health NZ hospitals, some with restrictions.
MPR
Major pathological response: 10% or less viable tumour in the resected specimen after neoadjuvant therapy.
Marjolin ulcer
cSCC arising in a scar, burn or chronic wound. High risk in NCCN and NZSCD; excluded from the main risk-factor meta-analysis.
ONTRANS
Randomised trial of nicotinamide in organ transplant recipients. Stopped early (n = 158); no reduction in keratinocyte cancers.
PDEMA
Peripheral and deep en face margin assessment: complete margin control, including Mohs and staged excision with en face sections.
PNI
Perineural invasion: tumour within or around a nerve sheath. The report should give calibre, depth, number of nerves and named-nerve involvement.
PORT
Postoperative (adjuvant) radiotherapy.
SLNB
Sentinel lymph node biopsy: mapping and removing the first draining node(s). No survival benefit has been shown in cSCC.
Special Authority
Pharmac’s criteria-based funding approval. Criteria are literal. No checkpoint inhibitor has a cutaneous SCC criterion.
acitretin
Oral retinoid used as chemoprevention in patients with multiple keratinocyte cancers. Teratogenic. Funded under Special Authority SA2024.
desmoplasia
Fibrous stroma around infiltrating tumour strands; RCPath defines desmoplastic cSCC as more than 30% desmoplastic stroma. A strong predictor of local recurrence.
differentiation
Histological grade (well, moderately, poorly differentiated), assigned by the worst area present, however small.
keratoacanthoma
Rapidly growing crateriform squamous tumour. Its separation from well-differentiated cSCC is unreliable, so it is excised early.
laCSCC
Locally advanced cSCC: extensive disease where surgery or radiotherapy may not cure, or would cause significant functional impairment (NCCN).
mTOR switch
Replacing a calcineurin inhibitor with an mTOR inhibitor (sirolimus, everolimus) in a transplant recipient to reduce new cSCC.
named nerve
A nerve with an anatomical name, identifiable clinically or on imaging, as opposed to an unnamed dermal twig.
pCR
Pathological complete response: no viable tumour in the resected specimen after neoadjuvant therapy.

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Unresolved as of 1 October 2026. The exact wording of the NCCN v2.2026 table and footnotes (seen only as a redraw). The EADO 2026 full text: recommendation wording, grades and figures beyond the abstracts, including the low-risk margin, nodal imaging, SLNB, adjuvant radiotherapy and adjuvant cemiplimab recommendations and the follow-up intervals. BAD 2020 wording (all BAD statements are from secondary summaries). The C-POST protocol’s PNI definition and whether transplant recipients were excluded. Whether cetuximab SA2401 would be accepted for a cutaneous head and neck primary. Whether a supplier access programme for cemiplimab operates in NZ. NZ trial availability on ANZCTR, which was not searched.