Incidence and Risk Factors

Basal cell carcinoma:

Basal cell carcinoma (BCC) is the most common type of skin cancer and the most common cancer in humans. Approximately 70-80% of all cases of NMSC are BCC, and annually approximately 200 in every 100,000 people will develop BCC. The majority of BCC’s develop in sun exposed areas such as the head and neck. These lesions are usually slow growing and rarely spread to other areas of the body. However, these tumors may invade locally into surrounding tissues causing a significant amount of tissue destruction. Therefore, these tumors must be treated when found.

Squamous cell carcinoma:

Squamous cell carcinoma is less common than BCC and accounts for approximately 20% of all cases of NMSC. As with BCC, this cancer is associated with sun exposure and lesions are commonly found on the head, neck, arms and legs. Squamous cell carcinoma may also develop in areas of chronic inflammation or scars, such as ulcers and burns. Squamous cell carcinoma is more likely than BCC to spread to other areas of the body. This occurs 2-3% of the time.

Risk factors for the development of BCC and SCC:

Skin type: People who are of white racial background are more likely to develop NMSC.

Sun exposure: The major risk factor for the development of NMSC is exposure to ultraviolet radiation in the form of sunlight.

Chronic scars: Squamous cell carcinoma of the skin may be found in association with chronic inflammatory wounds or scars.

Gender: Non-melanoma skin cancer is more common in men, likely due to greater sun exposure. The male to female ratio is 3:1.

Immunosuppression: Patients who are immunosuppressed are more likely to develop NMSC. These cancers are seen with increased frequency in patients who have undergone organ transplantation, especially SCC, and often these cancers are more aggressive in these patients.

Genetic predisposition: Several inherited genetic disorders are associated with a high rate of NMSC. These include xeroderma pigmentosum, nevoid basal cell syndrome, and albinism.


If a skin biopsy shows that NMSC is present, the doctor will need to perform additional tests to find out whether the cancer cells have spread to other areas of the body. This process is known as staging, and it is important for determining treatment and outcomes.

There are several important factors that are used in staging NMSC:

Tumor size: Tumor size is important in staging patients with NMSC who have localized disease. Patients with localized disease and tumors = 2 cm are stage I while those with tumors > 2 cm are stage II.

Local invasion: Non-melanoma skin cancers that have spread to involve nearby structures including muscle, cartilage, and bone are considered stage III.

Lymph nodes: If abnormal cells spread outside of the primary lesion, they most often go to the lymph nodes in the area of the tumor. Lymph nodes are small glands that are found all over the body and are involved in the body’s immune response. When lymph nodes are involved, the patient has a worse prognosis and therefore, a higher stage of disease. Lymph node involvement is classified as stage III.

Metastases: This occurs when the abnormal cells have spread beyond the primary melanoma lesion and the lymph nodes draining the tumor to involve other organs and distant lymph nodes in the body. Metastatic disease is classified as stage IV.

Using information on tumor size, lymph nodes, and metastases, patients can be staged.

Stage 0 (Carcinoma in Situ): Abnormal cells are only identified in the upper layer of the skin (epidermis).

Stage I: Tumor = 2 cm.

Stage II: Tumor > 2 cm.

Stage III: Patients with stage III NMSC have either abnormal cells that have spread to lymph nodes draining the tumor or abnormal cells that have locally invaded into nearby cartilage, muscle, or bone. Abnormal cells have not spread to other organs or distant lymph nodes.

Stage IV: Patients with stage IV NMSC have abnormal cells that have spread to distant organs or lymph nodes.

Symptoms and Diagnosis

While skin cancer may not cause any symptoms, some lesions may cause itching, bleeding, and tenderness. Any skin lesions that are new, change in size or color, or cause local symptoms should be evaluated by a physician.

When a person with a concerning skin lesion is seen by a doctor, the doctor will perform a history and physical examination. The doctor will ask questions related to the risk factors for skin cancer and will focus on specific changes in the lesion that is of concern. The physical examination will include a full body skin exam, as well as examination of any swellings in the neck, the underarm area, and the groin, which may indicate spread of the disease.

In order to diagnose skin cancer, a piece of tissue must be obtained. This is called a biopsy. For NMSC’s tissue may be obtained by shave, punch, or excision/incisional biopsy.

Shave biopsy: A shave biopsy is performed by using a scalpel to remove the superficial skin layers. This is usually done for superficial skin lesions. The biopsy area is injected with numbing medicine and then the scalpel is used to remove a tangential area of skin. This biopsy may not include all of the skin layers down to the fat layer. Shave biopsy sites are left open to heal and generally leave a small scar.

Punch biopsy: A punch biopsy is performed using a circular cutting device that takes out a cylinder of skin tissue. The biopsy device cuts through all layers of the skin using a circular motion down to the fat layer which is called the subcutaneous (below the skin) tissue. When performing a punch biopsy, a small amount of numbing medicine is injected into and around the lesion and then the core of tissue encompassing the lesion is removed. The skin defect is usually closed with 1 or 2 sutures. Punch biopsies are generally used in cases where the entire lesion may be removed by the punch biopsy device.

Excisional or incisional biopsy: An excisional or incisional biopsy is performed by using a scalpel (knife) to remove a sample of tissue. An excisional biopsy is generally used when the lesion is bigger than the usual punch biopsy devices but not so large that it will leave a large skin defect. An incisional biopsy is generally used for larger lesions when only a portion of the tissue is going to be sampled. In both cases, the biopsy area is injected with numbing medicine and then a piece of skin tissue is removed. As with the punch biopsy, the tissue sample will include all layers of the skin down to the fat layer. The biopsy site is then closed with several sutures.

Once a piece of the skin tissue is obtained, it is sent to a doctor who is specialized in looking at body tissues and can determine whether a skin cancer is present.


The mainstay of treatment for NMSC is surgical excision. There are several techniques that are used depending on the size and location of the lesion.


Excisional surgery: The majority of NMSC’s may be removed by surgical excision. Surgical excision may be performed in the office or in the operating room, depending on the size and location of the lesion. Recurrence rates after surgical excision are <10%.

Mohs micrographic surgery: Mohs micrographic surgery (MMS) is a specialized technique that is utilized for the removal of skin tumors and is the most accurate way to remove NMSC. Serial horizontal sections of tumor are removed and the margins of resection are immediately evaluated to determine if the entire tumor is removed. While the majority of NMSC may be excised using conventional excisional techniques without microscopic evaluation, there are some specific situations in which MMS is indicated. These include resection of lesions in cosmetically sensitive areas, lesions with high recurrence rates (midface and ears), tumors greater than 2 cm in size, recurrent tumors, tumors with aggressive histologic growth patterns, and tumors with ill-defined borders. The goal of MMS is to remove all tumor while preserving as much healthy tissue as possible. Mohs micrographic surgery is available through the Department of Dermatology at the University of Maryland.

Curettage and Electrodesiccation: Curettage and electrodesiccation is an additional surgical technique for removal of superficial NMSC. A curette, which is a cutting device, is used to scrape away the tumor cells, and then electrodessication is used to kill the surrounding cells. This is usually repeated 2-3 times to eliminate the entire tumor. This technique is only appropriate for superficial tumors that are not of an aggressive type.


Radiation therapy is the use of high-energy x-rays to kill cancer cells. Radiation may be used as the primary treatment for patients with NMSC or may be used in addition to surgical excision. The decision to use radiation as the primary treatment for NMSC depends on the size and location of the lesion and patient comorbidities. Radiation may also be considered for more aggressive tumors where there is evidence of nerve invasion or lymph node metastases.

Topical therapy

Topical 5-fluorouracil is the most commonly used chemotherapy agent for the treatment of NMSC. This agent is applied for 4-6 weeks. Because the depth of tissue penetration of 5-fluorouracil is limited, this treatment is only appropriate for very superficial BCC’s or SCC’s. This agent has also been used to treat actinic keratoses, which may develop into SCC. Imiquimod is another topical agent that stimulates the host antitumor immune response. This agent has been used for the treatment of actinic keratoses, superficial BCC and non-invasive (in situ) SCC.