Cutaneous squamous cell carcinoma

Last updated: November 29, 2023

Summarytoggle arrow icon

Cutaneous squamous cell carcinoma (cSCC) is the second most common keratinocyte carcinoma after basal cell carcinoma. The most important risk factors are cumulative UV exposure, chronic immunosuppression, and a history of precancerous skin lesions (e.g., actinic keratosis). cSCC lesions typically manifest as a friable nonhealing hyperkeratotic papule or plaque with central ulceration on sun-exposed areas of the body. Dermoscopy can be used to support the clinical diagnosis of suspicious lesions, but skin biopsy is required for diagnostic confirmation. Additional diagnostics (e.g., imaging, SLNB) may be required to evaluate for nodal and distant metastasis, especially in individuals with high-risk features of cSCC. Risk stratification of cSCC is used to classify the lesions as low-risk or high-risk for recurrence after excision and thereby guide management. Tumor resection (e.g., Mohs micrographic surgery, surgical excision) is the preferred treatment modality; radiotherapy can be considered if resection is not feasible. Patients with cSCC are at high risk for subsequent skin cancers. All patients should be screened for recurrence and the development of new skin cancers after treatment. Photoprotective measures should be recommended to all individuals for primary prevention and the prevention of recurrent or subsequent skin cancers.

See “Head and neck carcinomas” and “Anogenital manifestations of HPV infection” for diagnosis and management of squamous cell carcinoma of the head, neck, and genitals.

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Risk factorstoggle arrow icon

Clinical featurestoggle arrow icon

Precursor and early lesions

Invasive cSCC [2]

  • Characteristic features include:
  • Location [2]
    • Typically occurs on sun-exposed areas
      • Dorsal aspect of forearms and hands (most common)
      • Head, and neck (including ears and lip)
    • Atypical areas
      • Areas not exposed to the sun: more common in individuals with darker skin tones or chronic inflammatory skin conditions
      • Subungual and anogenital SCC: associated with high-risk HPV infection [1][3]

cSCC is more common South of the upper lip (i.e., it most commonly occurs on the forearms, unlike basal cell carcinoma, which most commonly occurs on the head and neck). [2]

Metastatic cSCC

Metastases occur in ∼ 3% of individuals with cSCC; risk is higher in immunosuppressed individuals. [2][7]

  • cSCC Can spread through the nervous, lymphatic, or vascular systems
  • Perineural invasion can manifest as pain, numbness, and/or weakness.
  • Most common sites for metastasis include lymph nodes (80%), lungs, liver, brain, and bone [7]

Subtypes and variantstoggle arrow icon

Keratoacanthoma [1][2][8]

Keratoacanthoma is a well-differentiated squamoproliferative keratotic lesion that is now considered a low-risk histologic variant of SCC. [1][2][8]

Epidemiology [8][9]

  • Common; true incidence is unknown
  • Most commonly occurs in adults > 40 years of age
  • >

Risk factors [8][9][10]

Clinical features [8][9][10]

  • Rapidly growing, firm, dome-shaped nodule or papule with a central keratotic plug (crateriform tumor)
  • Typically located on sun-exposed areas
  • Can be solitary (common) or multiple
  • Typically 1–2 cm in size; can grow up to 20 cm

Keratoacanthomas may grow by 1–2 cm over the course of weeks or months. [10]

Diagnostics [8][9][10]

Keratoacanthoma may be clinically indistinguishable from invasive cSCC on clinical examination and dermoscopy. Biopsy is required for diagnostic confirmation.

Differential diagnoses [10][13]

Treatment [8][10]

Keratoacanthoma should be treated as cSCC. [2]

Prognosis [8][9]

  • Spontaneous regression can occur within 12 months in some cases.
  • Rarely, metastasis can occur.
  • Risk of recurrence after excision: up to 8% [8]

Marjolin ulcer [6]

A Marjolin ulcer refers to the malignant transformation of preexisting chronic skin inflammation or scar tissue.

Clinical features



Diagnosticstoggle arrow icon

General principles [3][4][14]

Dermoscopy findings of cSCC [3][16][18]

  • Characteristic vascular features
    • Looped (hairpin) vessels and serpentine vessels
    • Glomerular vessels
    • Small dotted vessels
  • Pigmented features of cSCC [3]
    • Gray-brown homogeneous pigmentation
    • Small brown globules
  • Other features [18][19]
    • Keratin
    • Small white circles or white structureless areas [16]
    • Ulceration
    • Blood spots

Actinic keratosis has a strawberry pattern on dermoscopy: yellow or white dots or haloes on an erythematous background. [16]
Suspect invasive cSCC if looped and serpentine vessels are seen on dermoscopy. [3]

Skin biopsy [2][14]

Select a biopsy technique based on the clinical features of the lesion and procedural risks ; use shared-decision making.

  • Techniques:
  • Ensure adequate sample size and depth for histopathological examination; if not, a repeat biopsy may be required. [17]
  • To optimize the quality of the pathology report, the following information should be included with the biopsy samples: [17]

Perform a full-thickness excisional biopsy if there is any concern for malignant melanoma (e.g., pigmentation, ABCDE criteria). [2]

Pathologytoggle arrow icon

cSCC occurs as a result of malignant transformation of keratinocytes in the stratum spinosum (prickle cell layer) of the epidermis. These atypical keratinocytes appear as enlarged, polygonal cells with nuclear pleomorphism and atypical mitoses. [20]

Precancerous cSCC (Actinic keratosis)

Carcinoma in situ (Bowen disease)

Invasive cSCC

High-risk histological subtypes of cSCC [3]

Low-risk histological subtypes of cSCC [3]

Differential diagnosestoggle arrow icon

Stagingtoggle arrow icon

Assessment of disease extent [1][14]

Refer patients with high-risk features of cSCC to a specialist (e.g., oncologist) to evaluate for locoregional, nodal, and distant metastases. This may include:

A thorough clinical examination to assess for lymph node involvement, perineural invasion, local spread (e.g., to the parotid), and distant metastasis should be performed, especially in patients with high-risk features of cSCC. [1][14]

Staging [1][14][23][24]

There is currently no universally accepted staging system for cSCC. The most commonly used staging systems in the US are:

  • AJCC-8 : for head and neck cSCC; unsatisfactory as a prognostic tool
  • Brigham and Women's Hospital staging system : superior to AJCC-8 in the prognostication of localized cSCC

Risk stratification of cSCC [14]

To guide management decisions, stratifying cSCC based on the risk of recurrence, metastasis, and disease-related mortality is recommended. Risk stratification is based on clinical and histopathological features.

High-risk features of cSCC [1][2][14]
Tumor characteristics
  • ≥ 4 cm in size (any location) [4]
  • ≥ 2 cm in size and located on the trunk or extremities
  • ≥ 1 cm in size and located on the cheeks, forehead, scalp, neck, or pretibia
  • cSCC of any size located in the following areas:
    • H-zone of the face
      • Central face (i.e., eyelids, eyebrows, nose, lips, chin)
      • Temple, ears, pre or postauricular region, or mandible
    • Hands or feet
    • Genitals
  • Poorly defined borders
  • Recurrent lesion
  • Neurologic symptoms
  • Rapid growth
Histopathology features
Patient factors

Treatmenttoggle arrow icon

General principles [2][4][14]

Overview of treatment options [4][14]

Overview of treatment options for cSCC [4][14]
Indications Special considerations
Mohs micrographic surgery
  • Recommended for high-risk cSCC [4][14]
  • Preferred if minimal tissue excision is required [4]
  • Consider for management of positive margins after resection. [1][4]
  • Lowest recurrence rate of all treatment options
  • Limited availability
Surgical excision [2][14]
Curettage and
  • Contraindicated for tumors: [1][14]
    • On cosmetically sensitive areas
    • On hair-bearing skin
    • Extending beyond the dermis
  • If the subcutaneous layer is breached during C&E, surgical excision is recommended.
Radiotherapy (RT) [2][14]
  • Primary RT: Consider for localized cSCC if resection is not feasible. [1][4]
  • Consider adjuvant RT for: [1][4]
  • Lower cure rates than resection [2][14]
  • Typically used for adults > 60 years of age [2][4]
Cryotherapy [14]
  • Consider for low-risk cSCC if resection or RT is contraindicated or not feasible.
  • Lower cure rates than resection
Systemic therapy [2][4][14]
  • Consider if curative RT or resection is not feasible for:
    • High-risk locally advanced or metastatic cSCC [4]
    • Management of positive margins

Topical pharmacotherapy and photodynamic therapy are not recommended for the treatment of cSCC. Adjuvant photodynamic therapy after resection may be considered for high-risk cSCC lesions. [14]

Localized cSCC [1][4][14]

High-risk cSCC

  • Preferred: MMS
  • Alternatives
    • Surgical excision with wide margins; consider delayed closure until R0 resection is confirmed.
    • RT ± systemic therapy for patients who cannot undergo resection
  • Consider adjuvant RT for patients with perineural involvement.

Low-risk cSCC

  • Preferred
    • Standard surgical excision (4–6 mm margins) [1][14]
    • MMS
    • RT for patients who cannot undergo resection
  • Alternatives for small, superficial lesions in patients who cannot undergo resection

Locally advanced or metastatic cSCC [1][4][14]

Specialist referral and multidisciplinary care are recommended to consider the following options:

Follow-up for cSCC [1][4][14]

  • Screen for skin cancer every 3–12 months for 2 years.
  • Tailor the frequency of further follow-up visits to the individual's risk of new or recurrent skin cancers; for example:
    • Follow-up once every 2 years in patients with localized disease if initial follow-up was negative.
    • More frequent follow-up is recommended for patients with regional metastasis. [1]
  • Treat actinic keratoses at diagnosis.
  • Encourage adherence to photoprotective measures.
  • Educate patients and/or caregivers on self-examination to detect recurrence, new lesions, and lymph node enlargement.

A comprehensive skin examination and lymph node examination should be performed at each follow-up visit. [14]

Prognosistoggle arrow icon

  • 5-year survival rate: ≥ 90% [4]
  • Individuals with a history of cSCC are at an increased risk of developing subsequent cSCC and other skin cancers (BCC, melanoma). [1][14]
  • cSCC accounts for ∼ 20% of all deaths caused by skin cancers. [7]

Unresectable locoregional disease is the most common cause of cSCC-related mortality. [24]

Preventiontoggle arrow icon

Related One-Minute Telegramtoggle arrow icon

Referencestoggle arrow icon

  1. John Y.S. Kim, Et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018; 78 (3): p.560-578.doi: 10.1016/j.jaad.2017.10.007 . | Open in Read by QxMD
  2. Waldman A, Schmults C. Cutaneous Squamous Cell Carcinoma. Hematol Oncol Clin North Am. 2019; 33 (1): p.1-12.doi: 10.1016/j.hoc.2018.08.001 . | Open in Read by QxMD
  3. Burns C, Kubicki S, Nguyen QB, et al. Advances in Cutaneous Squamous Cell Carcinoma Management. Cancers (Basel). 2022; 14 (15).doi: 10.3390/cancers14153653 . | Open in Read by QxMD
  4. Ruiz ES, Karia PS, Besaw R, Schmults CD. Performance of the American Joint Committee on Cancer Staging Manual, 8th Edition vs the Brigham and Women’s Hospital Tumor Classification System for Cutaneous Squamous Cell Carcinoma. JAMA Dermatol. 2019; 155 (7): p.819.doi: 10.1001/jamadermatol.2019.0032 . | Open in Read by QxMD
  5. Firnhaber JM. Basal Cell and Cutaneous Squamous Cell Carcinomas: Diagnosis and Treatment. Am Fam Physician. 2020; 102 (6): p.339-346.
  6. Schmults CD, Blitzblau R, Aasi SZ, et al. NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022. J Natl Compr Canc Netw. 2021; 19 (12): p.1382-1394.doi: 10.6004/jnccn.2021.0059 . | Open in Read by QxMD
  7. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018; 78 (2): p.237-247.doi: 10.1016/j.jaad.2017.08.059 . | Open in Read by QxMD
  8. Brian Pekarek, Stacie Buck, Lawrence Osher. A Comprehensive Review on Marjolin's Ulcers: Diagnosis and Treatment. The Journal of the American College of Certified Wound Specialists. 2011; 3 (3): p.60-64.doi: 10.1016/j.jcws.2012.04.001 . | Open in Read by QxMD
  9. Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ. Early detection and treatment of skin cancer. Am Fam Physician. 2000; 62 (2): p.357-68, 375-6, 381-2.
  10. Grossman DC, Curry SJ, et al. Behavioral Counseling to Prevent Skin Cancer. JAMA. 2018; 319 (11): p.1134.doi: 10.1001/jama.2018.1623 . | Open in Read by QxMD
  11. Bibbins-Domingo K, Grossman DC, et al. Screening for Skin Cancer. JAMA. 2016; 316 (4): p.429.doi: 10.1001/jama.2016.8465 . | Open in Read by QxMD
  12. Sánchez G, Nova J, Rodriguez-Hernandez AE, et al. Sun protection for preventing basal cell and squamous cell skin cancers. Cochrane Database Syst Rev. 2016; 2016 (9).doi: 10.1002/14651858.cd011161.pub2 . | Open in Read by QxMD
  13. Caudill J, Thomas JE, Burkhart CG. The risk of metastases from squamous cell carcinoma of the skin. Int J Dermatol. 2022; 62 (4): p.483-486.doi: 10.1111/ijd.16164 . | Open in Read by QxMD
  14. Firnhaber JM. Diagnosis and treatment of Basal cell and squamous cell carcinoma. Am Fam Physician. 2012; 86 (2): p.161-8.
  15. Dinnes J, Deeks JJ, Chuchu N, et al. Visual inspection and dermoscopy, alone or in combination, for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev. 2018; 2018 (12).doi: 10.1002/14651858.cd011901.pub2 . | Open in Read by QxMD
  16. Marghoob AA, Usatine RP, Jaimes N. Dermoscopy for the family physician. Am Fam Physician. 2013; 88 (7): p.441-50.
  17. Kim JYS, Kozlow JH, Mittal B, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. 2018; 78 (3): p.540-559.doi: 10.1016/j.jaad.2017.10.006 . | Open in Read by QxMD
  18. Mayeaux EJ. The Essential Guide to Primary Care Procedures. LWW ; 2015
  19. Rosendahl C, Cameron A, Argenziano G, Zalaudek I, Tschandl P, Kittler H. Dermoscopy of Squamous Cell Carcinoma and Keratoacanthoma. Arch Dermatol. 2012; 148 (12): p.1386.doi: 10.1001/archdermatol.2012.2974 . | Open in Read by QxMD
  20. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nature Reviews Disease Primers. 2020; 6 (1).doi: 10.1038/s41572-020-00224-3 . | Open in Read by QxMD
  21. Bath-Hextall FJ, Matin RN, Wilkinson D, Leonardi-Bee J. Interventions for cutaneous Bowen's disease. Cochrane Database Syst Rev. 2013; 2013 (6): p.CD007281.doi: 10.1002/14651858.CD007281.pub2 . | Open in Read by QxMD
  22. Kwiek B, Schwartz RA. Keratoacanthoma (KA): An update and review. J Am Acad Dermatol. 2016; 74 (6): p.1220-33.doi: 10.1016/j.jaad.2015.11.033 . | Open in Read by QxMD
  23. Saavedra A, Et al.. Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology, Ninth Edition. McGraw Hill Professional ; 2023
  24. Higgins JC, Maher MH, Douglas MS. Diagnosing Common Benign Skin Tumors. Am Fam Physician. 2015; 92 (7): p.601-7.
  25. 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
  26. Muir-torre syndrome. . Accessed: July 11, 2023.
  27. Wolff K, Johnson RA, Suurmond D. Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology. McGraw-Hill Medical ; 2005

Icon of a lock3 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