Cutaneous squamous cell carcinoma

Last updated: August 3, 2022

Summarytoggle arrow icon

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer after basal cell carcinoma. It occurs as a result of the malignant transformation of keratinocytes in the stratum spinosum (prickle cell layer) of the epidermis. Risk factors for malignant transformation include exposure to sunlight, chemical carcinogens, precancerous lesions of the skin (e.g., actinic keratosis), and sites of skin damage (e.g., scars, burns, ulcers). Although the classic clinical presentation is a painless, nonhealing, bleeding ulcer with everted edges, cSCC may initially present as plaques, nodules, or even warty lesions. All suspicious skin lesions should be biopsied to confirm the diagnosis, determine the histological grade and stage the tumor. Further evaluation (e.g., imaging, lymph node biopsies) may be required in cases with high-risk features to rule out regional and/or systemic metastasis. The treatment of choice is surgical excision of the lesion with a wide safety margin. Mohs micrographic surgery, which is associated with lower rates of tumor recurrence and better cosmetic results, is increasingly used instead of standard surgical excision. Radiotherapy and/or chemotherapy may be used as adjuvants in cases with high-risk features.


Epidemiological data refers to the US, unless otherwise specified.


  • Appearance
    • Initial appearance may be plaque-like, nodular, papillomatous, and/or verrucous
    • All forms eventually ulcerate
  • Location
    • Most commonly on the face and neck
    • Typical locations include the lower lip, ears, and hands.
  • Growth and spread

The classic clinical presentation of cSCC is a painless, nonhealing, bleeding ulcer.

Cutaneous Squamous cell carcinoma is more common South (below) of the upper lip.


Marjolin ulcer: an aggressive form of cSCC that typically develops from areas of chronically damaged skin such as ulcers (e.g., pressure ulcers, osteomyelitis) and scars (e.g., burn scars)



A biopsy should be performed on any suspicious skin lesion!


Broder histological grading

  • Grade 1 (highly differentiated): > 75% of keratinocytes are well-differentiated
  • Grade 2 (moderately differentiated): 50–75% of keratinocytes are well differentiated
  • Grade 3 (poorly differentiated): 25–50% of keratinocytes are well differentiated
  • Grade 4 (undifferentiated/anaplastic): < 25% of keratinocytes are well-differentiated

See Differential diagnosis of common skin cancers.


The differential diagnoses listed here are not exhaustive.

  • Surgical excision of the lesion along with a rim of normal skin is the primary method of treatment.
    • Cryotherapy or curettage with electrodesiccation may be used in the case of carcinoma-in-situ; its use is contraindicated in patients with invasive cSCC.
    • Mohs micrographic surgery
      • Increasingly used in place of standard surgical excision.
      • Tumor is removed layer by layer, and each layer is examined for tumor cells.
  • Radiotherapy
    • Adjuvant treatment in cases with high-risk features
    • Primary treatment when tumors are inoperable (e.g., patient is unfit for surgery).
  • Chemotherapy (e.g., 5-fluorouracil, epidermal growth factor inhibitors)


  1. Schwartz RA. Keratoacanthoma: a clinico-pathologic enigma.. Dermatol Surg. 2004; 30 (2 Pt 2): p.326-33; discussion 333. doi: 10.1111/j.1524-4725.2004.30080.x . | Open in Read by QxMD
  2. Lim JL, Asgari M. Clinical features and diagnosis of cutaneous squamous cell carcinoma (SCC). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: March 8, 2017. Accessed: March 11, 2017.
  3. Keratoacanthoma. Updated: January 1, 1999. Accessed: February 21, 2018.
  4. Lim JL, Asgari M. Epidemiology and risk factors for cutaneous squamous cell carcinoma. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: January 3, 2017. Accessed: March 11, 2017.
  5. Tampa M, Mitran CI, Mitran MI, et al. The Role of Beta HPV Types and HPV-Associated Inflammatory Processes in Cutaneous Squamous Cell Carcinoma. Journal of Immunology Research. 2020; 2020 : p.1-10. doi: 10.1155/2020/5701639 . | Open in Read by QxMD
  6. Guideline on the diagnosis and treatment of Invasive Squamous Cell Carcinoma of the Skin. . Accessed: March 11, 2017.
  7. Williams NS, Bulstrode C, O'Connell PR. Bailey & Love's Short Practice of Surgery. CRC Press ; 2013
  8. Chartier TK, Aasi SZ. Treatment and prognosis of cutaneous squamous cell carcinoma. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: November 21, 2015. Accessed: February 17, 2017.
  9. Nuño-González A, Vicente-Martín FJ, Pinedo-Moraleda F, López-Estebaranz JL. High-risk cutaneous squamous cell carcinoma. Actas Dermosifiliogr. 2012; 103 (7): p.567-578. doi: 10.1016/j.adengl.2012.08.004 . | Open in Read by QxMD
  10. Fischer C. Master the Boards USMLE Step 2 CK. Kaplan Publishing ; 2013
  11. Najjar T. Cutaneous Squamous Cell Carcinoma. Cutaneous Squamous Cell Carcinoma. New York, NY: WebMD. Updated: June 14, 2016. Accessed: February 17, 2017.
  12. Jiang SIB. Mohs Surgery. Mohs Surgery. New York, NY: WebMD. Updated: January 22, 2016. Accessed: February 17, 2017.
  13. Mohs Micrographic Surgery: How It Works . Updated: November 12, 2008. Accessed: February 17, 2017.

3 free articles remaining

You have 3 free member-only articles left this month. Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer