Cutaneous squamous cell carcinoma

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.

• Second most common form of skin cancer after basal cell carcinoma
• Sex: ♂ > ♀ (2:1)
• Incidence: increases with age, closeness to the equator, and among light-skinned individuals

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Malignant transformation of keratinocytes in the stratum spinosum (prickle cell layer) of the epidermis.
• Risk factors:
  • UV exposure (especially among light-skinned individuals): most significant risk factor
  • Exposure to ionizing radiation
  • Exposure to chemical carcinogens (e.g., coal tars through smoking, arsenic)
  • Areas of chronically damaged skin, nonhealing wounds ; (see Marjolin ulcer below)
  • Chronic immunosuppression (e.g., HIV, transplant patients who receive immunosuppressive therapy)
  • Precancerous skin lesions (especially actinic keratosis and Bowen disease) ^[2]

References:^[1][3]

• Appearance
  • Initial appearance may be plaque-like, nodular, papillomatous, and/or verrucous
  • All forms eventually ulcerate
    • Ulcers are typically red with 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
  • Typical locations include the lower lip, ears, and hands.
• Growth and spread
  • Locally invasive but grows slowly
  • The overall rate of metastasis is 2%
  • Regional metastasis to lymph nodes is more common than hematogenous 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.

References:^[4][5]

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)

References:^[5]

• Carcinoma-in-situ (Bowen disease): Atypical keratinocytes are confined to the epidermis.
• Invasive cSCC: Atypical keratinocytes cross the basement membrane of the epidermis and invade the dermis.

References:^[5]

• 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 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]

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.

• Basal cell carcinoma: Basal cell carcinomas grow more slowly than cSCC and do not metastasize to lymph nodes.
• Keratoacanthoma
  • Definition: a cutaneous low-grade tumor
    • More common in middle-aged and elderly individuals ^[6]
    • Associated with Muir-Torre syndrome
  • Characteristic features
    • Rapid growth (within 2–3 months) in areas of skin exposed to the sun (e.g., the ears)
    • Lesion: round dome-shaped, erythematous nodule with central crater
    • Histology: central, hyperkeratotic crater surrounded by squamous epithelium
  • Treatment: The tumor usually heals without treatment.; Nonetheless, surgical removal is preferred because keratoacanthoma histologically resembles a cSCC, which is malignant.
• Actinic keratosis; , seborrheic keratosis

References:^[5][7]

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)
  • Indicated in case of systemic metastasis
  • Adjuvant treatment in cases with high-risk features.

References:^[4][8][9]