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Dermatology
Plastic Surgery
Oncology

Squamous Cell Carcinoma (Skin)

High EvidenceUpdated: 2025-12-24

On This Page

Red Flags

  • Rapidly growing tender nodule
  • Perineural Invasion (Numbness/Weakness)
  • Palpable Lymphadenopathy (Metastasis)
Overview

Squamous Cell Carcinoma (Skin)

1. Clinical Overview

Summary

Cutaneous Squamous Cell Carcinoma (cSCC) is a malignant tumour arising from epidermal keratinocytes. It is the second most common skin cancer (after BCC). Unlike BCC, cSCC has significant metastatic potential (2-5% overall, higher in high-risk features). Early complete excision is curative, but neglected lesions can be fatal. [1,2]

Key Features

  • Appearance: Fleshy, erythematous nodule with a Hyperkeratotic (scaly/crusty) surface. Often ulcerated or tender.
  • Sites: Sun-exposed areas (Face, Scalp, Ears, Hands).
  • Precursors:
    • Actinic Keratosis: Dry, rough spots (low risk).
    • Bowen's Disease: Carcinoma in situ (full thickness but no invasion).

Clinical Pearls

The Transplant Risk: Organ transplant recipients on long-term immunosuppression (e.g., Tacrolimus/Cyclosporine) have a 65-100 fold increased risk of cSCC. In these patients, the ratio flips (SCC becomes more common than BCC), and the tumours are more aggressive.

High Risk Sites: "Mask Area" of face.

  • Ear: High risk of metastasis to cervical nodes.
  • Lip: High risk of metastasis to submental nodes.

Marjolin's Ulcer: An aggressive SCC arising in a chronic wound or old burn scar (e.g., 20 years after the burn).


2. Epidemiology

Demographics

  • Incidence: Rising rapidly.
  • Age: Elderly (>70).
  • Skin Type: Fitzpatrick I/II (Fair skin that burns easily).
  • Gender: Male > Female (2:1) - likely occupational sun exposure.

Risk Factors

  1. UV Radiation: Cumulative lifetime exposure (unlike BCC which is intermittent bursts).
  2. Immunosuppression: Transplant, HIV, CLL.
  3. Chronic Inflammation: Leg ulcers, burn scars.
  4. HPV: Types 16/18.

3. Pathophysiology

Mechanism

  • UV-B radiation induces DNA damage (thymine dimers) in keratinocytes.
  • Mutation of the p53 tumour suppressor gene is the hallmark early event ("Guardian of the genome").
  • Clonal expansion leads to invasion of the dermis.

4. Clinical Presentation

Symptoms

Signs


Growth
Rapid (weeks/months) - faster than BCC.
Pain
Often tender (BCCs are usually painless).
Bleeding
Spontaneous ulceration.
5. Clinical Examination
  • Look: Ill-defined margins? Scaly?
  • Feel: Stretch the skin. Is it tethered to deep structures?
  • Nodes: Mandatory lymph node exam.

6. Investigations

Diagnosis

  • Dermoscopy: White circles, glomerular vessels. (Less specific than for BCC/Melanoma).
  • Biopsy: GOLD STANDARD.
    • Excision Biopsy: Preferred (remove whole lesion).
    • Incision/Punch: If lesion is large, to confirm type before major surgery.

Staging

  • Ultrasound / CT: Indications:
    • Palpable lymph nodes.
    • Large tumour (>2cm).
    • Bone invasion suspected.

7. Management

Management Algorithm

        SUSPICIOUS KERATOTIC LESION
                    ↓
             DERMATOLOGY REFERRAL
             (2 Week Wait)
                    ↓
        BIOPSY / EXCISION CONFIRMS SCC
                    ↓
             RISK STRATIFICATION
        ┌───────────┴───────────┐
     LOW RISK               HIGH RISK
  (less than 2cm, Well diff,       (>2cm, Poor diff,
   No invasion)            Ear/Lip, Immuno)
        ↓                       ↓
  SURGICAL EXCISION       MDT DISCUSSION
  (4mm margins)                 ↓
                          WIDE EXCISION
                          (6mm+ margins)
                          +/- RADIOTHERAPY
                          +/- NODAL SURGERY

1. Surgical Excision (Standard of Care)

  • Low Risk: 4mm clinical margin.
  • High Risk: 6-10mm margin.
  • MOHS Micrographic Surgery: Used for high-risk facial tumours to ensure clear margins whilst sparing tissue.

2. Radiotherapy

  • Indications:
    • Patient unfit for surgery.
    • Adjuvant treatment (post-op) if margins involved or Perineural Invasion.

3. Systemic Therapy (Advanced)

  • Cemiplimab: PD-1 inhibitor (Immunotherapy) for metastatic cSCC.

8. Complications
  • Metastasis: To regional lymph nodes (Parotid, Cervical, Axillary).
  • Perineural Invasion: Tracking along nerves (Mental nerve, Facial nerve). Causes numbness/palsy. Extremely high risk.
  • Recurrence: Local recurrence after incomplete excision.

9. Prognosis and Outcomes
  • Overall: 5-year survival >90%.
  • Metastatic: 5-year survival less than 40%.

10. Evidence and Guidelines

Key Guidelines

GuidelineOrganisationKey Recommendations
cSCC ManagementBAD (British Assoc Derm)Margins of 4-6mm. MDT for high risk.
StagingAJCC 8th EditionDefines T staging based on size and invasion.

Landmark Evidence

1. Immunosuppression Reduction

  • Studies show that reducing immunosuppression (or switching from Calcineurin inhibitors to Sirolimus) in transplant patients can reduce the rate of new SCCs.

11. Patient and Layperson Explanation

What is Squamous Cell Carcinoma?

It is a skin cancer that grows from the outer horny layer of the skin cells. It is caused by sun damage accumulating over your whole life.

Is it dangerous?

Yes, it is more serious than the common "Basal Cell" cancer because it has a small risk (about 1 in 20) of spreading to lymph glands and other parts of the body.

How do we treat it?

We usually cut it out with stitches. Because it has "roots", we take a safety margin of healthy skin around it to be sure we got it all.

Will it come back?

If we get it all, it shouldn't come back in that spot. However, because your skin has sun damage, you are at high risk of getting new ones elsewhere. Use high factor sunscreen every day.


12. References

Primary Sources

  1. Keohane SG, et al. British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma. Br J Dermatol. 2021.
  2. Work Group, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018.

13. Examination Focus

Common Exam Questions

  1. Diagnosis: "Tender, crusted nodule on ear?"
    • Answer: SCC.
  2. Risk Factor: "Renal transplant patient?"
    • Answer: SCC risk is 100x higher.
  3. Prognosis: "Poor prognostic factors?"
    • Answer: Size >2cm, Depth >4mm, Perineural invasion, Ear/Lip site, Poor differentiation.
  4. Precursor: "Rough sandpaper skin?"
    • Answer: Actinic Keratosis.

Viva Points

  • Keratoacanthoma: A rapidly growing (weeks) variant that looks like a volcano with a keratin plug. Historically thought benign/self-resolving, now treated as a variant of SCC and excised.
  • Perineural Invasion: Why ask about numbness? If the tumour invades a nerve, it can track all the way to the skull base. MRI is needed.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.

Last updated: 2025-12-24

At a Glance

EvidenceHigh
Last Updated2025-12-24

Red Flags

  • Rapidly growing tender nodule
  • Perineural Invasion (Numbness/Weakness)
  • Palpable Lymphadenopathy (Metastasis)

Clinical Pearls

  • **High Risk Sites**: "Mask Area" of face.
  • * **Ear**: High risk of metastasis to cervical nodes.
  • * **Lip**: High risk of metastasis to submental nodes.
  • **Marjolin's Ulcer**: An aggressive SCC arising in a chronic wound or old burn scar (e.g., 20 years after the burn).
  • Female (2:1) - likely occupational sun exposure.

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines