About Skin Cancer

Nonmelanoma skin cancer primarily comprises basal cell carcinoma and squamous cell carcinoma. Rates of skin cancer have been described as epidemic, with the incidence of all skin cancers rising at 4% to 5% each year.

Frequency

United States

In 1994, the annual incidence in the United States ranged from 81-136 cases per 100,000 population for men and 26-59 cases per 100,000 population for women.

International

Prevalence rates of squamous cell carcinoma vary in different countries. The highest incidence occurs in Australia, where the age-adjusted incidence has been calculated to be 1332 cases per 100,000 population for men and 755 cases per 100,000 population for women.

One reason for the rising incidence of skin cancer is an increase in sun exposure in the general population. Some postulate that ozone depletion may be intensifying UV exposure. Other contributing factors for the increased incidence of skin cancer include the advancing age of the US and world population, earlier and more frequent diagnosis due to enhanced public awareness of skin cancer, and more frequent skin examinations by physicians and patients.

The definitive treatment for most skin cancers involves the complete surgical removal of the lesion, ensuring that the margins are free of tumor cells. Other treatment options include curettage and electrodessication, excision, Erbium laser, and phototherapy; and postoperative margin assessment, radiation therapy, and superficial therapies.

Basal Cell Skin Cancer

Frequency

United States

The annual incidence of basal cell carcinoma (BCC) is approximately 900,000 cases (550,000 in men, 350,000 in women). The age-adjusted incidence per 100,000 white individuals is 475 cases in men and 250 cases in women. The estimated lifetime risk of BCC in the white population is 33-39% in men and 23-28% in women.

International

Prevalence rates of basal cell carcinoma vary in different countries. The highest incidence occurs in Australia, where the age-adjusted incidence has been calculated to be 1332 cases per 100,000 population for men and 755 cases per 100,000 population for women.

Squamous Cell Skin Cancer

Squamous cell carcinoma (SCC) is the second most common form of skin cancer and accounts for 20% of skin cancers. Squamous cell carcinoma frequently arises on the sun-exposed skin of middle-aged and elderly individuals.

Most squamous cell carcinomas are readily identified and removed in the physician's office as a minor surgical procedure. Larger and more invasive lesions may require aggressive surgical management, radiation therapy, or both. High-risk squamous cell carcinoma carries a significant risk of metastasis and, as such, requires careful evaluation and treatment.

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

Age older than 50 years

Male sex

Light skin; blonde or light brown hair; green, blue, or gray eyes

Skin that sunburns easily (Fitzpatrick skin types I and II)

Geography (closer to the equator)

History of prior non-melanoma skin cancer

Exposure to UV light (high cumulative dose of sunshine, tanning beds, or medical UV treatments)

Exposure to chemical carcinogens (eg, arsenic, tar)

Exposure to ionizing radiation (medical treatments, occupational or accidental radiation exposure)

Chronic immunosuppression

Chronic scarring conditions

Certain genodermatoses

Human papillomavirus (HPV) infection (specific subtypes)

Pathophysiology

Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes. Most squamous cell carcinomas arise from sun-induced precancerous lesions known as actinic keratoses (AKs). Patients with multiple AKs are at increased risk for developing squamous cell carcinoma. Squamous cell carcinoma is capable of locally infiltrative growth, spread to regional lymph nodes, and distant metastasis, most often to the lungs, brain, and liver.

Mortality/Morbidity

The majority of squamous cell carcinomas are readily treated by surgeons in their offices, and produce few sequelae. A subset of high-risk tumors causes most of the morbidity and the mortality associated with squamous cell carcinoma. Such tumors may cause extensive destruction of local tissue, and their removal may create a substantial cosmetic deformity.

The overall risk of metastasis for squamous cell carcinoma is in the range of 2-6%. Lymph node metastasis is associated with significant morbidity; however, 5-year survival rates as high as 73% have been achieved with the combination of surgical lymphadenectomy and radiation therapy. Once lung, brain, or liver metastasis occurs the disease is virtually incurable.

Race

Squamous cell carcinoma is the second leading cause of skin cancer in whites. Persons of Irish or Scottish ancestry have the highest prevalence in the United States. Squamous cell carcinoma is relatively rare in people of African and Asian descent, although it is the most common form of skin cancer in these groups. Squamous cell carcinoma in blacks carries a higher mortality rate, perhaps due to delayed diagnosis because tumors are more likely to occur in sun-protected areas, including the scalp and sites of previous injury and scarring.

Sex

Squamous cell carcinoma occurs in men 2-3 times more frequently than it does in women, most likely as a result of greater cumulative lifetime UV exposure.

Age

The typical age at presentation is approximately 70 years; however, this varies widely, and, in certain high-risk groups (eg, organ transplant recipients [OTRs], patients with epidermolysis bullosa), squamous cell carcinoma often manifests at a much younger age.

Clinical History

A detailed patient history often reveals the presence of one or more risk factors for squamous cell carcinoma (SCC). Most squamous cell carcinomas are discovered by patients and are brought to a physician's attention by the patient or a relative. The typical squamous cell carcinoma manifests as a new or enlarging lesion that concerns the patient. Squamous cell carcinoma is typically a slow-growing malignancy, but some lesions enlarge rapidly. Although most squamous cell carcinoma patients are asymptomatic, symptoms such as bleeding, weeping, pain, or tenderness may be noted, especially with larger tumors. Numbness, tingling, or muscle weakness may reflect underlying perineural involvement, and this history finding is important to elicit because it is associated with a very poor prognosis.

Physical Finding

Typical squamous cell carcinoma tumor: The characteristic invasive squamous cell carcinoma is a raised, firm, pink-to-flesh–colored keratotic papule or plaque arising on sun-exposed skin. Approximately 70% of all squamous cell carcinomas 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, squamous cell carcinoma 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.

Lymphadenopathy: With any invasive (not in situ) squamous cell carcinoma, regional lymph nodes should be examined. Lymph node enlargement must be further evaluated by fine-needle aspiration (FNA) or nodal biopsy. A complete metastatic work-up is warranted if the FNA is positive.

Major Causative Factors

Sun Exposure: The most common type of squamous cell carcinoma is the sun-induced type. A history of long-term sun exposure dating back to childhood is frequently elicited. Many patients report having experienced multiple blistering sunburns during their lifetime, while others may have used indoor tanning beds or received UV light therapy (eg, psoralen plus UVA [PUVA] for psoriasis). 

UV sunlight exposure: The component of sunlight believed to be most important in cutaneous carcinogenesis is UVB (290-320 nm), which is both an initiator and a promoter of carcinogenesis. UVB-induced photocarcinogenesis appears to work by suppressing the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of immunosuppressive cytokines, and elicits DNA damage.

Fair complexion: Individuals with Fitzpatrick skin types I and II account for most of the patients who develop squamous cell carcinoma.

Immune suppression: Patients should always be questioned about possible sources of immunosuppression. A history of solid-organ transplantation, hematologic malignancy (particularly chronic lymphocytic leukemia [CLL]), HIV infection or AIDS, or long-term use of immunosuppressive medications (eg, as treatment for an autoimmune condition) may be elicited.

Marjolin ulcer: This eponym refers to a squamous cell carcinoma that arises from chronically scarred or inflamed skin. Patients may report a change in the skin (eg, induration, elevation, ulceration, weeping) at the site of a preexisting scar or ulcer. The latency period is often 20-30 years; therefore, the diagnosis requires a high index of clinical suspicion.

HPV-associated squamous cell carcinoma: Virally induced squamous cell carcinoma mostcommonly manifests as a new or enlarging warty growth on the penis, vulva, perianal area, or periungual region. Patients often present with a history of "wa rts" that have been refractory to various treatment modalities in the past. A history of previously documented genital HPV infection is common.

Chemical carcinogens: Exposure to arsenic is a well-established cause of cutaneous squamous cell carcinoma and internal cancers. Today, the main source of arsenic is contaminated well water, although arsenic may also be found in traditional Chinese medicines. Other carcinogens associated with squamous cell carcinoma include polycyclic aromatic hydrocarbons such as tar, soot, and pitch. Police and firefighters are a high risk group for this causation related cancer.

Iatrogenic immunosuppression: The use of immunosuppressive medications to prevent rejection in OTRs is associated with a 65- to 250-fold increased risk of developing squamous cell carcinoma compared with the general population. The primary risk factor in these patients is cumulative lifetime UV exposure in combination with having skin type I or II. This risk also increases with the number of years posttransplantation, presumably because of the cumulative effects of prolonged immunosuppressive therapy. The greatest risk occurs in heart transplant patients, with diminishing risk seen in recipients of kidney and liver transplants, which correlates with the degree of immunosuppression (ie, number and/or dosage of medications) typically required to prevent rejection in these patient populations.

Chronic inflammation: Chronic inflammation, irrespective of the underlying etiology, may lead to the development of squamous cell carcinoma. Both noninfectious inflammatory diseases and chronic infections have been associated with squamous cell carcinoma.