What are the key clinical features that differentiate cutaneous squamous cell carcinoma from other skin lesions?

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 16 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

Key clinical features that differentiate cutaneous squamous cell carcinoma (cSCC) from other skin lesions include:

  • A persistent, non-healing, scaly or crusted lesion often with an irregular surface, which may ulcerate or bleed spontaneously, distinguishing it from benign lesions like actinic keratosis or seborrhoeic keratosis .
  • Lesions typically present as firm, erythematous papules, plaques, or nodules that may be tender or painful, unlike basal cell carcinoma which often appears pearly and translucent .
  • Rapid growth over weeks to months is more characteristic of cSCC compared to slower-growing benign lesions or other skin cancers .
  • Commonly arises on sun-exposed areas such as the face, ears, neck, and hands, which helps differentiate it from other lesions with different distribution patterns .
  • Dermoscopy may reveal specific features such as glomerular or dotted vessels and scaling, which are more suggestive of cSCC compared to other lesions .
  • Histologically, cSCC shows invasive atypical keratinocytes with keratin pearl formation, which is distinct from other skin cancers and benign lesions .
  • In situ variants like Bowen disease present as well-demarcated, erythematous, scaly plaques, which can be differentiated clinically and histologically from invasive cSCC and other dermatoses .

In summary, the combination of a persistent, scaly, sometimes ulcerated lesion on sun-exposed skin, rapid growth, characteristic dermoscopic vascular patterns, and histological confirmation are key to differentiating cSCC from other skin lesions .

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