Cutaneous Squamous Cell Carcinoma Differential Diagnoses

Updated: Sep 24, 2021
  • Author: Jeffery W Wells, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
  • Print

Diagnostic Considerations

Although the typical patient with cutaneous squamous cell carcinoma (cSCC) is of northern European descent and presents with a family history of skin cancer, a personal history of previous skin cancer, and/or an extensive history of sun exposure, a detailed history and physical examination is crucial (see Presentation). In addition, the clinician should be aware of the risk factors for high-risk disease (see Prognosis).

Marjolin ulcer appears as a new area of induration, elevation, or ulceration, at the site of a preexisting scar or ulcer. The diagnosis of Marjolin ulcer should be considered in any ulcer that fails to heal with standard therapy.

Pseudoepitheliomatous hyperplasia (PEH) is a histologic finding in keratoacanthoma and SCC, as well as in certain other reactions, such as tattoo reactions. The clinician must determine whether the PEH is associated with cancer. In addition, with lesions containing PEH in patients with a history of lupus, the clinician must differentiate between lesions that are definitely SCC and lesions of hypertrophic lupus that are mimicking SCC or keratoacanthoma.

Other conditions to be considered

The following conditions should also be considered when evaluating a patient with suspected SCC:

  • Cancerous lesions: Sebaceous cell carcinoma and rhabdomyosarcoma

  • Congenital tumors: Dermoids, dermolipomas, and episcleral osseous choristoma

  • Conjunctival degeneration: Pinguecula and amyloidosis

  • Hereditary lesions: Benign hereditary intraepithelial dyskeratosis

  • Lymphoid tumors: Lymphoid neoplasia, benign reactive lymphoid hyperplasia, and leukemic infiltrates

  • Neuroectodermal tumors: Nevus, primary acquired melanosis, and melanoma

  • Papillomas: Human papillomavirus (HPV) ̶ induced papillomas

  • Pseudocancerous lesions: Pseudoepitheliomatous hyperplasia and keratoacanthoma

  • Vascular lesions: Angioma, lymphangioma, Kaposi sarcoma, and pyogenic granuloma

  • Xanthomatous lesions: Juvenile xanthogranuloma and fibrous xanthoma

Differential Diagnoses