II. Epidemiology

  1. Age-adjusted Incidence: 100-150 per 100,000 persons/year
    1. Affects 400,000 in U.S. per year
    2. Results in 3000 U.S. Deaths per year
  2. Gender: Twice as common in males
  3. Incidence in Skin of Color
    1. Ethnicities with CSCC as most common Skin Cancer
      1. Native Americans
      2. Black patients (Peak Incidence at ages 40-49)
    2. Ethnicities with CSCC as second most common Skin Cancer
      1. Chinese and Japanese (peaks after age 60 years old)
      2. Hispanic patients

III. Risk Factors

  1. See Nonmelanoma Skin Cancer
  2. Exposure to UVB
  3. Actinic Keratoses (precursor to CSCC)
    1. Malignant transformation rate varies from <10% in 10 years to as high as 20% per year
    2. Malignant transformation of Actinic Keratoses are responsible for 60% of CSCC cases
  4. Immunosuppression
    1. HIV Infection
    2. Organ transplant recipients (65 fold increased risk related to Immunosuppression)
      1. Lesion onset at 2-4 years after Transplantation and risk increases with time
  5. Advanced age
  6. Closer distance to the equator
  7. Chronically diseased or injured skin (e.g. Skin Ulcerations, sinus tracts)
  8. Xeroderma Pigmentosum

IV. Pathophysiology

  1. Arises from superficial layers of Keratinocytes
    1. Neoplastic transformation is triggered by UV radiation exposure
    2. CSCC is on the same spectrum as Actinic Keratoses
      1. Actinic Keratoses proliferate and extend into the Dermis at which point they are defined as SCC
    3. CSCC spreads by local infiltration
      1. Spreads along tissue planes and structures such as nerves, arteries and veins
  2. Precursor lesions
    1. Actinic Keratoses (60% of CSCC arises from actinics)
    2. Radiation and burn scars

V. Symptoms

  1. Nonhealing lesion that frequently bleeds without significant Trauma

VI. Signs

  1. Location
    1. Sun exposed areas
  2. Characteristics
    1. Firm, smooth hyperkeratotic Papule, Nodule, patch or Plaque on indurated base
    2. Central ulceration and crusting is common
    3. Thick white scale may be present
    4. Fleshy heaped-up edges of lesion
  3. Variants
    1. Verrucous carcinoma
      1. Wart-like CSCC lesion with higher malignant potential
    2. Bowen's Disease (Cutaneous Squamous Cell Carcinoma In Situ)
      1. Slow-growing, scaly red Plaque on sun-exposed skin
    3. Cutaneous horn (keratin horn, cornu cutaneum)
      1. Hyperkeratotic growth with similar appearance to a horn
      2. Starts as Actinic Keratosis and progresses to Squamous Cell Carcinoma

VII. Diagnosis: Skin Biopsy

  1. Raised lesion: Shave Biopsy if not pigmented
    1. Any suspicion of Melanoma needs full-thickness sample
  2. Flat lesions: Punch Biopsy or full excision
    1. Complete excision of small lesions with Punch Biopsy
    2. Punch Biopsy of the most abnormal appearing aspects of larger lesions

VIII. Differential Diagnosis

  1. See Nonmelanoma Skin Cancer
  2. Keratocanthoma

IX. Grading

  1. Sample inadequate for micro-staging
    1. Consider obtaining narrow-margin Excisional Biopsy
  2. Low Risk
    1. Well differentiated or moderately differentiated
    2. No High risk histologic subtypes (see high risk subtypes below)
    3. Superficial depth <2 mm (or Clark Level 1, 2 or 3)
    4. No perineural, lymphatic or vascular involvement
  3. High Risk
    1. Poorly differentiated
    2. Depth >= 2mm or Clark 3-4
      1. Depth should not include scale, crust or parakeratosis
      2. Measured from base of ulcer (if present)
    3. High risk histologic subtypes
      1. Adenoid or Acantholytic
      2. Adenosquamous (with mucin production)
      3. Desmoplastic
      4. Metaplastic (Carcinosarcomatous)

X. Management

  1. Mohs' Microographic Surgery
    1. Preferred as first-line therapy in most cases of Cutaneous Squamous Cell Carcinoma
    2. Indications
      1. Large lesions
        1. Central face, periorbital, periauricular: >6 mm
        2. Cheeks, forehead, neck, scalp: >10 mm
        3. Trunk, extremities: >20 mm
      2. Indistinct margins
      3. Recurrent lesions
      4. Lesion in close proximity to eyes, nose, mouth
      5. Preserve cosmetic appearance
    3. References
      1. Martinez (2001) Mayo Clin Proc 76:1253 [PubMed]
  2. Surgical excision
    1. Low-risk primary CSCC should be excised with 4-6 mm margin of uninvolved skin
    2. Complete excision recommended over ED&C
      1. Due to risk of metastases
    3. Imperative to confirm negative margins
    4. Indications
      1. Small lesions less than size criteria for Moh's
      2. Slow growing, well differentiated lesions
      3. Negative for neural or vascular invasion
  3. Radiation Therapy
    1. Indicated in age over 55 years with CSCC in high risk, surgically difficult areas

XI. Course

  1. More rapid growth than Basal Cell Carcinoma
  2. Locally destructive Skin Cancer
  3. Metastases
    1. Ocurs in 3-5% of cases to distant sites via hematogenous spread
    2. Risk factors (may confer up to 40% metastases risk)
      1. Large tumors >2 cm in diameter (3 fold increased risk of metastasis)
      2. Involvement of ear, lip or chronically diseased or injured skin
      3. Immunosuppression

XII. Prevention

  1. See Sun Exposure (lists general preventive measures)
  2. See Sunscreen

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