Squamous Cell Carcinoma — USMLE Step 2 CK Guide 2026

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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.

Key points

Cutaneous SCC is the second most common skin cancer and arises from epidermal keratinocytes
Classic lesion: erythematous scaly papule, plaque, nodule, or nonhealing ulcer on sun-exposed skin
Major risk factors: cumulative UV exposure, actinic keratoses, immunosuppression, chronic wounds, HPV, arsenic, and radiation
Diagnosis is biopsy; treatment is excision or Mohs depending on risk site and tumor features
High-risk features include lip/ear, size >2 cm, depth >2 mm, poor differentiation, perineural invasion, recurrence, and immunosuppression

Overview

Cutaneous squamous cell carcinoma is a malignant proliferation of epidermal keratinocytes. It commonly develops from actinic keratoses on chronically sun-damaged skin but may also arise in scars, ulcers, burns, radiation fields, genital HPV-associated lesions, or immunosuppressed patients. Unlike basal cell carcinoma, SCC has meaningful metastatic potential, particularly when high-risk features are present. SCC in situ is called Bowen disease; invasive SCC breaches the basement membrane.

Epidemiology

SCC is common in fair-skinned older adults with cumulative UV exposure. Organ transplant recipients have markedly increased risk and more aggressive SCC because of chronic immunosuppression. Chronic inflammatory or scar-associated SCC is called Marjolin ulcer and may behave aggressively. Lower lip SCC is associated with sun exposure and tobacco. Anogenital SCC is often HPV-associated. Keratoacanthoma is a rapidly growing crateriform lesion with central keratin plug that is commonly treated as a variant of SCC because clinical distinction can be unreliable.

Clinical Features

Symptoms

Persistent scaly, crusted, tender, or bleeding lesion on sun-exposed skin

Nonhealing ulcer in chronic wound, burn scar, or radiation field

Rapidly growing crateriform nodule with central keratin plug (keratoacanthoma pattern)

Lip lesion that ulcerates, bleeds, or forms a firm plaque

Numbness, tingling, pain, or weakness near lesion suggests perineural invasion

Signs

Erythematous hyperkeratotic papule, plaque, nodule, or ulcer

Firm indurated base or heaped-up border

Regional lymphadenopathy suggests nodal spread

Actinic damage: solar lentigines, elastosis, multiple actinic keratoses

High-risk locations: ear, lip, genitalia, hands/feet, scars, chronic ulcers

Investigations

First-line

BiopsyShave, punch, or excisional biopsy depending on lesion morphology and depth. Histology confirms invasive SCC vs SCC in situ vs hypertrophic actinic keratosis

Full-skin and lymph node examinationEvaluate surrounding field cancerization and regional nodes, especially for high-risk tumors

Histologic risk assessmentDepth, differentiation, perineural invasion, lymphovascular invasion, and margins determine recurrence/metastatic risk

Second-line

ImagingUltrasound, CT, or MRI if deep invasion, perineural symptoms, bony invasion, or nodal disease is suspected

Medication/immunosuppression reviewTransplant immunosuppression, chronic lymphocytic leukemia, and systemic immunosuppression increase aggressiveness

Specialist

Sentinel lymph node biopsyNot routine; may be considered only in selected very high-risk tumors by specialists

Management

AAD Cutaneous Squamous Cell Carcinoma Guideline

Localized low-risk SCC

Standard surgical excision with appropriate margins and histologic margin assessment
Electrodesiccation and curettage may be considered for carefully selected low-risk lesions on non-hair-bearing sites
Treat surrounding actinic keratoses and sun damage to reduce future keratinocyte carcinoma risk

High-risk SCC

Mohs micrographic surgery is preferred for high-risk sites, poorly defined borders, recurrent tumors, aggressive histology, or tissue-sparing locations
Evaluate regional lymph nodes; image if nodes are abnormal or deep/perineural invasion suspected
Multidisciplinary management for nodal disease, large tumors, perineural invasion, or immunosuppressed patients

SCC in situ and selected superficial disease

Options include excision, topical 5-fluorouracil, imiquimod, curettage, or photodynamic therapy depending on site and diagnosis
Invasive disease must not be treated as benign dermatitis; biopsy persistent plaques

Advanced disease and prevention

Unresectable, locally advanced, or metastatic cSCC may be treated with PD-1 inhibitor therapy such as cemiplimab or pembrolizumab
Sun protection, avoidance of tanning beds, and routine surveillance
Transplant patients may require dermatology co-management and immunosuppression modification in recurrent aggressive SCC

Complications

Local recurrence: Especially after incomplete treatment or aggressive histology
Perineural invasion: Pain, numbness, cranial neuropathy, and higher recurrence risk
Nodal metastasis: More likely from lip, ear, deep, poorly differentiated, recurrent, or immunosuppressed tumors
Distant metastasis: Lung and other sites in advanced disease
Field cancerization: Multiple AKs and future SCCs in chronically sun-damaged skin

USMLE Step 2 CK Exam Tips

1Scaly hyperkeratotic nonhealing lesion on sun-exposed skin = SCC until proven otherwise
2Pearly papule with telangiectasias = BCC; scaly ulcerated plaque/nodule = SCC
3Actinic keratosis is premalignant for SCC, not melanoma
4SCC in a chronic burn scar or ulcer = Marjolin ulcer; more aggressive
5Rapid crateriform nodule with keratin plug = keratoacanthoma; treat/excise because it resembles SCC
6Immunosuppressed transplant recipient + multiple SCCs = high-risk behavior
7High-risk SCC of lip or ear: choose Mohs/specialist management rather than simple reassurance

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