January 16, 2007

Epitheliomas, Basal Cell

Synonyms and related keywords: basal cell epitheliomas, basal cell cancer of the skin, basaloma, basalioma, rodent ulcer, basal cell carcinoma, BCC, skin cancer, skin tumor, basal cell nevus syndrome, Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome, NBCCS, ultraviolet light, UV light, trichoblastic carcinoma, trichoblastoma, fibroepithelioma of Pinkus, epithelial tumor


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).


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.

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.


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.


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:


Molluscum Contagiosum

Other Problems to be Considered:

Intradermal nevus
Lichenoid benign keratosis
Sebaceous hyperplasia
Squamous cell carcinoma
Fibroepithelioma of Pinkus (see Histology)


Lab Studies:

Imaging Studies:


Histologic Findings: A histopathologic examination of paraffin-embedded sections of BCC usually reveals solid cellular strands, collections of cells with dark-staining nuclei and scant cytoplasm. The peripheral cell mass is in a palisade arrangement that resembles the basal layer of the epidermis, sometimes with pseudocystic aspects, and with a variable number of mitoses. The characteristic mucinous stroma develops around the invading tumor. Each subtype of BCC has a specific histologic pattern (ie, desmoplastic reaction of the morpheaform type, stromal islands separated by basal cells strands of the fibroepithelial type). Cells from recurrent BCC often show squamous aspects.

According to some studies, including a recent paper that appeared in The American Journal of Dermatopathology, the so-called fibroepithelioma of Pinkus, considered to be a premalignant skin condition, must be considered as a fenestrated variant of BCC.

Staging: BCC rarely metastasizes and usually is not staged, unless the cancer is very large and is suspected of spreading to other parts of the body. BCC staging may be similar to the staging of squamous cell carcinoma, according to the following scheme:

  • Stage 0: Cancer involves only the epidermis and has not spread to the dermis.
  • Stage I: Cancer is not large (ie, less than 2 cm) and has not spread to the lymph nodes or other organs.
  • Stage II: The cancer is large (ie, >2 cm) but has not spread to lymph nodes or other organs.
  • Stage III: The cancer has spread to tissues beneath the skin (eg, muscle, bone, cartilage), and/or has spread to regional lymph nodes, but has not spread to other organs.
  • Stage IV: The cancer can be any size and has spread to other organs.


Medical Care: The therapy of BCC varies according to cancer size, depth, and location. Dermatologists may perform many of the therapies in an outpatient setting. Most therapies are well established and widely applied; yet researchers still are studying some (eg, photodynamic therapy with photosensitizers) and awaiting further reports. Ideally, the treatment options should be evaluated jointly among surgeon, dermatologist, and radiotherapist on the basis of histologic diagnosis.

Surgical Care: As already reported, knowledge of the behavior of the different clinical and pathologic types of BCC is essential in choosing the appropriate therapy. The traditional surgical options involve the use of simple excision, cryosurgery, electrodesiccation, and curettage. BCC recurrence after irradiation makes surgery mandatory.


Because of surgery efficacy and good patient prognosis, drugs usually are not administered. Drugs and external beam radiotherapy are useful in patients with recurrence or advanced and destructive disease (eg, rodent ulcer, widespread metastases).

Tretinoin, bexarotene, and isotretinoin are being studied as potential therapeutic options. These are mediators of cell differentiation and proliferation, apoptosis, and reproduction. They induce cancer cells to mature, thereby eliminating abnormal proliferation. Therapeutic trials are ongoing in selected patients.

Interferons (alfa and beta) are also being used experimentally. These drugs usually act similarly to native interferons. In vitro, interferon beta seems to have greater antiproliferative effects than interferon alfa.

Because of the experimental therapeutic application of retinoids and interferons, no concordance exists about choice of therapeutic regimens.

Drug Category: Topical antineoplastics -- Topical administration of antineoplastic drugs stops cellular proliferation without (or minimizing) adverse effects.
Drug Name
Fluorouracil (Efudex, Fluoroplex) -- Response to 5-FU identified by degree of blistering, erosion, and necrosis of lesion. After this evolution ends, re-epithelization begins, which may continue 1-2 months after treatment. Treatment may cause local itching, pain, and hyperpigmentation. Used topically for management of superficial BCCs. Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid, inhibiting thymidylate synthetase, and subsequently affecting cell proliferation.
Only the 5% strength recommended.
Adult DoseApply topically bid for minimum of 3 wk in amount sufficient to cover lesions; therapy may be required for as long as 10-12 wk
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; potentially serious infections; pregnancy
InteractionsNone reported
Pregnancy X - Contraindicated in pregnancy
PrecautionsInstruct patient to avoid sun exposure, which may exacerbate necrotic reaction of treated area; inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increase in reaction


Further Outpatient Care:




Patient Education:

  • The American Cancer Society recommends a dermatologic examination every 3 years for patients aged 20-40 years and every year for patients older than 40 years.
  • For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Skin Cancer and Skin Biopsy.


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