INTRODUCTION	Section 2 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Background: Basal cell carcinoma (BCC) is the most common skin tumor. Tumor size can vary from a few millimeters to several centimeters in diameter. BCC is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells, small round cells found in the lower layer of the epidermis. Basal cells invade the dermis but seldom invade other parts of the body. Although BCC rarely spreads to other parts of the body, tumors can continue to grow, making surgical removal essential. If BCC is not diagnosed early and removed surgically, it can cause severe disfigurement.

BCC has a high frequency rate in adult males who have a long history of unprotected exposure to ultraviolet (UV) light. BCC can develop on unexposed areas; cases of BCC of the prostate have been reported. In a few patients, the contributing factors are contact with arsenic, tar, coal, paraffin, certain types of industrial oil, radiation exposure, scars (ie, burn complications), xeroderma pigmentosum, vaccinations, or even tattoos.

The DNA of certain genes is often damaged in patients with BCC; therefore, inheritance may be a factor. Most DNA alterations result from damage caused by exposure to sunlight.

Pathophysiology: The incidence of BCC increases with age, and most cases occur in patients older than 55 years; however, the damaging effects of the sun begin at an early age. The results may not appear for 20-30 years.

Patient geographical location affects the risk of developing skin cancer. In fact, BCC is related to lifetime exposure to UV radiation and a history of sunburn. The damaging effects of the sun are cumulative. The skin can repair superficial damage, but the underlying damage remains, including DNA damage. The damage worsens with each successive sun exposure, causing a lifetime progression. This damage reduces the ability of DNA to control cell growth and division and, in some situations, this progression results in cancer.

Almost all forms of BCC have mutations in the gene encoding the Hedgehog (Hh) receptor molecule, a signaling pathway playing a pivotal role in cell differentiation. At least three forms of this protein are known: sonic HH (SHH), Indian HH (IHH), and desert HH (DHH).

Frequency:

• In the US: Researchers report nearly 800,000 new cases of BCC each year (ie, approximately 2% of all cancer deaths).

• Internationally: The highest rates of skin cancer occur in South Africa and Australia, areas that receive high amounts of UV radiation. BCC accounts for 80% of all skin cancers but is the least likely cancer to behave in a malignant fashion and metastasize. BCC differs from squamous cell carcinoma, which accounts for 16% of skin cancers, because squamous cell carcinoma is much less common and more life threatening.

Mortality/Morbidity: Sunburns appear to increase the risk of BCC; however, this association is difficult to prove since most sunburns occur when patients are children. BCC risk is higher in farmers, fishermen, and other patients with frequent but intermittent sun exposure.

Race: The risk of BCC is greater for people who have type 1 or type 2 skin. BCC is the most common skin cancer in whites and is very rare in people with skin that is darkly pigmented.

• Type 1 skin - People with very fair skin, red or blond hair, freckles, always burn, never tan

• Type 2 skin - People with fair skin, burn easily, tan minimally

Sex: Although women are reporting cases of BCC more than in the past, men still outnumber them significantly. The male-to-female ratio is approximately 2.1:1.

Age: Patients aged 50-80 years are affected most often (mean age, 55 y); however, BCC can develop in teenagers and now appears frequently in fair-skinned patients aged 30-50 years.

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

History: People who sunburn are more likely to develop skin cancer than those who do not; however, sunlight damages the skin with or without sunburn. Consider BCC in any patient with a history of a sore or skin anomaly that does not heal within 3-4 weeks and occurs on sun-exposed skin, especially if it is dimpled in the middle. These tumors may take many months or years to reach even 1 cm in diameter.

Physical:

• Tumor characteristics

• BCC mostly occurs on the face, head (scalp included), neck, and hands. BCC rarely develops on the palms and soles.

• BCC usually appears as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury.

• BCCs may have one or more visible and irregular blood vessels, an ulcerative area in the center that often is pigmented, and black-blue or brown areas.

• Large BCCs may have oozing or crusted areas. The lesion is not painful, grows slowly, and does not itch or hurt.

• BCC subtypes

• The nodular subtype is the most common and specific form of BCC. Nodular BCC typically appears as a white-grayish, firm nodule (eg, similar to a mushroom cap), often is centrally ulcerated, and typically has enrolled and well-defined margins.

• The morpheaform subtype is the most difficult subtype to diagnose. This subtype typically appears as a scarring, firm plaque but, because of indistinct clinical tumor margins, is difficult to treat adequately with traditional therapies.

• The superficial subtype often is multiple, most often developing on the upper trunk or shoulders. The tumor grows slowly and appears as a pink or brown scaly patch, sometimes with a raised border.

• The sclerosing subtype is the most destructive form of BCC and is a variant of the nodular subtype. The sclerosing subtype involves a firm, large area, which is gray-whitish in color, with ill-defined margins. If untreated, ulcerations occur, causing a deep and large erosion of the soft tissues (eg, dermis, muscle, connective fascia, aponeurosis) and bone under the skin.

• BCC also is described as a basal cell nevus syndrome (ie, Gorlin syndrome), an autosomal dominant inherited condition that cannot be distinguished histologically from an ordinary tumor. The gene responsible for this syndrome is located on chromosome 9q, and chromosome abnormalities develop in some patients. Multiple BCCs, from one to hundreds, may occur in patients with this syndrome. Multiple BCCs begin to appear after puberty on the face, trunk, and extremities. Mental retardation may occur but is uncommon. In many cases the tumors are highly invasive and involve areas of the face, especially the regions around the eyes and nose. Other associated features of the Gorlin syndrome (fortunately uncommon) include the following:

• Congenital agenesis of the corpus callosum and medulloblastoma

• Odontogenic jaw cysts

• Bifid ribs and pectus excavatum

• Absent or undescended testes

• Mesenteric lymphatic cysts

• Palmar and plantar pits

• Ectopic calcification (particularly of the falx cerebri)

• Ocular and skeletal abnormalities (eg, hypertelorism, shortening of the fourth and fifth metacarpals)

Causes: Recent studies demonstrate a high incidence of p53 gene mutations in BCC. Researchers speculate that UV sunlight may play an important role in the genesis of this mutation; however, genetic involvement has been demonstrated in the Gorlin syndrome only. The following factors contribute to the risk of developing BCC:

• Skin type

• Amount and nature of accumulated sun exposure over lifetime, especially during childhood

• Personal and family skin cancer history

• Past medical history

• Occupational and recreational activities

• Patient lifestyle (eg, amount of sun exposure)