INTRODUCTION	Section 2 of 11
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Background: Basal cell carcinoma (BCC) is the most common cutaneous malignancy in humans. These tumors typically appear on sun-exposed skin, are slow growing, and rarely metastasize. Neglected tumors can lead to significant local destruction and even disfigurement.

Pathophysiology: Although the exact etiology of BCC is unknown, a well-established relationship exists between BCC and the pilosebaceous unit, as tumors are most often discovered on hair-bearing areas. Tumors are currently believed to arise from pluripotent cells (which have the capacity to form hair), sebaceous glands, and apocrine glands. Tumors usually arise from the epidermis or the outer root sheath of a hair follicle.

Frequency:

• In the US: Each year in the United States, 900,000 people are diagnosed with BCC (550,000 male, 350,000 female). The estimated lifetime risk of BCC in the white population is 33-39% for men and 23-28% for women.

Mortality/Morbidity: Although BCC is a malignant neoplasm, it rarely metastasizes. The incidence of metastatic BCC is estimated at less than 0.1%. The most common sites of metastasis are the lymph nodes, the lungs, and the bones. Typically, basal cell tumors enlarge slowly and relentlessly and tend to be locally destructive. Periorbital tumors can invade the orbit, leading to blindness, if diagnosis and treatment are delayed. Perineural invasion can occur, leading to loss of nerve function.

Race: Although BCC is observed in people of all races and skin types, it is most often found in light-skinned individuals; dark-skinned individuals are rarely affected.

Sex: Historically, men are affected twice as often as women. The higher incidence in men is probably due to increased recreational and occupational exposure to the sun, although these differences are becoming less significant with changes in lifestyle.

Age: The likelihood of developing BCC increases with age. With the exception of basal cell nevus syndrome, BCC is rarely found in patients younger than 40 years.

	CLINICAL	Section 3 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

History: Patients often complain of a slowly enlarging lesion that does not heal and that bleeds when traumatized. As tumors most commonly occur on the face, patients often give a history of an acne bump that occasionally bleeds.

• Patients often have a history of chronic sun exposure.

• Recreational sun exposure (eg, sunbathing, outdoor sports, fishing, boating)

• Occupational sun exposure (eg, farming, construction)

• Occasionally, patients have a history of exposure to ionizing radiation. X-ray therapy for acne was commonly used until 1950.

• Occasionally, patients have a history of arsenic intake; arsenic is found in well water in some parts of the United States.

Physical: Clinical presentation of BCC varies by type.

• Nodular BCC

• Nodular BCC is the most common type of BCC and usually presents as a round, pearly, flesh-colored papule with telangiectases. As it enlarges, it frequently ulcerates centrally, leaving a raised, pearly border with telangiectases, which aids in making the diagnosis.

• Most tumors are observed on the face, although the trunk and extremities also are affected.

• Cystic BCC

• An uncommon variant of nodular BCC, cystic BCC is often indistinguishable from nodular BCC clinically, although it might have a polypoid appearance.

• Typically, a bluish-gray cyst-like lesion is observed. The cystic center of these tumors is filled with clear mucin that has a gelatin-like consistency.

• Pigmented BCC

• Pigmented BCC is an uncommon variant of nodular BCC that has brown-black macules in some or all areas, often making it difficult to differentiate from melanoma.

• Typically, some areas of these tumors do not retain pigment; pearly, raised borders with telangiectases that are typical of a nodular BCC can be observed. This aids clinically in differentiating this tumor from a melanoma.

• Morpheaform (sclerosing) BCC

• Morpheaform BCC is an uncommon variant in which tumor cells induce a proliferation of fibroblasts within the dermis and an increased collagen deposition (sclerosis) that clinically resembles a scar. The tumor appears as a white or yellow, waxy, sclerotic plaque that rarely ulcerates.

• Because the tumor infiltrates in thin strands between collagen fibers, treatment is difficult, and the clinical margins are difficult to distinguish. Mohs micrographic surgery is the treatment of choice for this type of BCC.

• Superficial BCC

• Superficial BCC clinically appears as an erythematous, well-circumscribed patch or plaque, often with a whitish scale. Occasionally, minute eschars may appear within the patch or plaque.

• The tumor appears multicentric, with areas of clinically normal skin intervening among clinically involved areas.

Causes: The exact cause of BCC is unknown, although environmental factors that are believed to predispose patients to this disorder include the following:

• Exposure to sunlight, the most frequent association (UVB, 290-320 nm, which causes sunburn, is believed to play a greater role in the development of BCC than UVA.)

• Exposure to artificial ultraviolet light (eg, tanning booths, ultraviolet light therapy)

• Ionizing radiation exposure (eg, x-ray therapy for acne)

• Arsenic exposure through ingestion (eg, arsenic used as a medicinal agent, predominantly Fowler's solution of potassium arsenite that was used to treat many disorders, including asthma and psoriasis). A contaminated water source has been the most common source of arsenic ingestion.

• Immunosuppression: Immunosuppression has been associated with a modest increase in the risk of BCC. Therefore, recipients of organ or stem cell transplants have a higher lifetime risk of developing BCC.

• Xeroderma pigmentosum: This autosomal recessive disease results in the inability to repair UV-induced DNA damage. Pigmentary changes are seen early in life followed by the development of BCC, squamous cell carcinoma, and malignant melanoma. Other features include corneal opacities, eventual blindness, and neurological deficits.

• Nevoid BCC syndrome (basal cell nevus syndrome, Gorlin syndrome): This autosomal dominant disorder results in the early formation of multiple odontogenic keratocysts, palmoplantar pitting, intracranial calcification, and rib anomalies. Various tumors such as medulloblastomas, meningioma, fetal rhabdomyoma, and ameloblastoma also can occur.

• Bazex syndrome: Features include follicular atrophoderma ("ice pick" marks, especially on dorsal hands), multiple BCCs, and local anhidrosis (decreased or absent sweating).

• History of previous nonmelanoma skin cancer (BCC or squamous cell carcinoma): Persons who have been diagnosed with one nonmelanoma skin cancer are at increased risk of developing additional tumors in the future. The risk of developing new nonmelanoma skin cancers is reported to be 35% at 3 years and 50% at 5 years after an initial skin cancer diagnosis.