Squamous cell carcinoma (SCC) is the second most common form of skin cancer and frequently arises on the sun-exposed skin of middle-aged individuals. Estimated annual incidence of squamous cell carcinoma in the United States is 107 cases per 100,000 people.  People who have fair skin, light hair, and blue, green, or gray eyes are at highest risk of developing the disease.

Squamous cell carcinomas may occur on all areas of the body including the mucous membranes and genitals, but are most common in areas frequently exposed to the sun, such as the rim of the ear, lower lip, face, bald scalp, neck, hands, arms and legs.

Squamous cell carcinoma can occur either de novo i.e. in the absence of a precursor lesion or from sun-induced precancerous lesions known as actinic keratoses (AKs).  Patients with multiple AKs are at increased risk of developing squamous cell carcinoma.  Other precancerous conditions include actinic cheilitis, Bowen’s disease, leukoplakia and others.

Risk Factors

General risk factors associated with the development of squamous cell carcinomas are as follows:

• Age older than 50 years
• Male sex
• Fair skin (i.e., burns easily, never or rarely tans)
• Geography (closer to the equator)
• History of prior non-melanoma (squamous cell  or basal cell) skin cancer
• Exposure to UV light (high cumulative dose) including tanning beds
• Exposure to chemical carcinogens (eg., arsenic, tar)
• Exposure to ionizing radiation
• Chronic immunosuppression
• Chronic scarring condition
• Human papilloma virus (HPV) infection (specific subtypes)

Clinical Presentations

Several clinical presentations of squamous cell carcinomas are possible:

•  A new and/or scaly enlarging patch.  Most SCCs grow slowly, some subtypes may enlarge rapidly.
• A persistent, scaly red patch with irregular borders that sometimes crusts or bleeds.
• An elevated growth with a central depression that occasionally bleeds. A growth of this type may rapidly increase in size.
• An open sore that bleeds and crusts and persists for weeks.
• A wart-like growth that crusts and occasionally bleeds.

Although most squamous cell carcinomas are asymptomatic, symptoms such as bleeding, weeping, pain or tenderness may occur.  Numbness, tingling, or muscle weakness though rare may reflect underlying perineural involvement.

If readily and properly treated most squamous cell carcinomas produce few sequelae.  Untreated squamous cell carcinomas may cause extensive destruction of tissue, and its delayed removal may entail substantial cosmetic deformity.

MANAGEMENT OPTIONS

The choice of treatment is based on the type, size, location, and depth of penetration of the tumor, as well as the patient’s age and general health.

Treatment can almost always be performed on an outpatient basis in a physician’s office or at a clinic. A local anesthetic is used during most surgical procedures.

Squamous cell carcinoma treatment modalities and associated cure rates are listed below.

1. Mohs Micrographic surgery (LINK)

• • For SCC less than 2 cm cure rate is 98%
  • For SCC greater than 2 cm cure rate is 75%
  • Poorly differentiated (by histological assessment) cure rate is 67%

2. Excision

• • Best for SCC less than 2cm

3. Non-surgical modalities (cryotherapy- spraying with liquid nitrogen, electrodessication and currettage)

• • For well-differentiated SCC (determined by tumor histology) 81% cure rate
  • For SCC less than 2 cm cure rate is 58%
  • For poorly differentiated SCC (determined by tumor histology) cure rate is 46%

4. Radiation

• • Recommended for nerve involvement and regional metastatic disease

5. Photodynamic therapy (PDT)

• • PDT treatment is not yet FDA-approved for squamous cell carcinoma, and while it may be effective with early, noninvasive tumors, overall recurrence rates vary considerably (from 0 to 52 percent), so the technique is not currently recommended for invasive squamous cell carcinoma.

6. Topical medications including 5-fluorouracil (5-FU, Carac, Efudex) and imiquimod (Aldara, Zyclara). Both medications are FDA-approved for treatment of actinic keratoses and superficial basal cell carcinomas, are also being tested for the treatment of some superficial squamous cell carcinomas. Successful treatment of Bowen’s disease, a noninvasive squamous cell carcinoma, has been reported. However, invasive squamous cell carcinoma should not be treated with 5-FU.

Risk of Metastasis

The overall risk of metastasis for SCC is in the range of 0.3-16%; however, this rate may be as high as 47% for certain high-risk tumor subtypes.  When metastasis occurs, squamous cell carcinomas frequently can be life-threatening. About 2,500 deaths result each year in the U.S.

Risk of metastasis is increased with:

• Size greater than 2 cm
• Location (lips, ears, eyelids, genitals)
• Depth of invasion
• Presence of neural (skin nerve) involvement
• Immunosuppression
• Recurrence

Most common metastasis site is lymph nodes followed by the lung.

10-year survival for regional metastasis is 20% and for distant metastasis is 10%

Prevention and Recurrence

A person who has had one squamous cell cancer is at an increased risk of developing another, especially in the same skin area or nearby. That is usually due to the face that the skin has already suffered irreversible sun damage.

Thus, it is crucial to pay particular attention to any previously treated site, and any changes noted should be shown immediately to a physician.  Squamous cell carcinomas on the nose, ears, and lips are especially prone to recurrence. Even if no suspicious signs are noticed, regularly scheduled follow-up visits including total-body skin exams are an essential part of post-treatment care.

Subtypes of SCC

• SCC in situ (SCCIS): SCCIS defined histologically by atypia involving the full thickness of the epidermis (top layer of skin) but without invasion into the dermis.
• Actinically derived SCC: The most common type of SCC is the sun-induced type.
• Invasive SCC: The invasive SCC is a raised, firm, pink-to-flesh–colored keratotic papule or plaque arising on sun-exposed skin. Approximately 70% of all SCCs occur on the head and neck, with an additional 15% found on the upper extremities. Surface changes may include scaling, ulceration, crusting, or the presence of a cutaneous horn. Less commonly, SCC may manifest as a pink cutaneous nodule without overlying surface changes. A background of severely sun-damaged skin, including solar elastosis, mottled dyspigmentation, telangiectasia, and multiple AKs, is often noted.
• Periungual SCC: Periungual SCC typically mimics a verruca (wart).
• Marjolin ulcer: This subtype of SCC appears as a new area of induration, elevation, or ulceration at the site of a preexisting scar or ulcer.
• Perioral SCC: SCC of the lip usually arises on the vermillion border of the lower lip, close to the midline. The precursor lesion is actinic cheilitis, which manifests as xerosis, fissuring, atrophy, and dyspigmentation and which is analogous to AK of the skin.
• Verrucous carcinoma (VC): VC is a subtype of SCC that can be locally destructive but rarely metastasizes. Lesions appear as exophytic, fungating, verrucous nodules or plaques, which may be described as “cauliflower-like”.
• Anogenital SCC: SCC in the anogenital region. Associated symptoms include pain, pruritus, and intermittent bleeding.
• HPV-associated SCC: Virally induced SCC most commonly manifests as a new or enlarging warty growth on the penis, vulva, perianal area, or periungual region.