• Clinical science

Cutaneous squamous cell carcinoma (cSCC)

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer after basal cell carcinoma. It occurs as a result of 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, non-healing, 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. Moh's 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.

Epidemiology

  • Second most common form of skin cancer after basal cell carcinoma
  • Sex: > (2:1)
  • Incidence: increases with age
  • Greater incidence near the equator and among whites

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[2][1]

Clinical features

  • Appearance
    • Initial appearance may be plaque-like, nodular, papillomatous, and/or verrucous
    • All forms eventually ulcerate.
      • The ulcer typically has everted edges.
      • The floor of the ulcer resembles granulation tissue and bleeds easily.
      • The skin around the ulcer is inflamed and indurated.
  • Location
    • Most commonly on the face and neck
    • A typical location is the lower lip.
  • Growth and spread

The classic clinical presentation of cSCC is a painless, non-healing, bleeding ulcer.

References:[3][4][5][6]

Subtypes and variants

Marjolin's 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)

References:[6]

Stages

References:[6]

Diagnostics

  • Biopsy: should extend into the midreticular dermis for suspicious lesions
    • Techniques
      • Punch biopsy
      • Wedge biopsy may also be considered, especially for larger lesions (e.g., Marjolin's ulcer)
      • Excisional biopsy in some cases
      • Shave biopsy is generally only considered for carcinoma-in-situ
    • Findings
      • Atypical keratinocytes: polygonal cells with atypical nuclei
      • Keratin pearls (also called epithelial nests): deposits of keratin that are surrounded by concentric layers of atypical keratinocytes
  • Further evaluation may be indicated in cases with high-risk features to look for regional and/or systemic metastasis.
    • Imaging (e.g., CT, MRI)
    • Lymph node biopsies, FNAC

A biopsy should be performed on any suspicious skin lesion!
References:[5][6]

Pathology

Broder's 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

Differential diagnoses

References:[6][7]

The differential diagnoses listed here are not exhaustive.

Treatment

  • 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 case of carcinoma-in-situ; its use is contraindicated in case of invasive cSCC.
    • Moh's micrographic surgery is increasingly used in place of standard surgical excision.
  • 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)
    • Indicated in case of systemic metastasis
    • Adjuvant treatment in cases with high-risk features.

References:[3][5][8][9][10]