- Basal-cell carcinoma
Basal-cell carcinoma Classification and external resources
A basal-cell carcinoma
ICD-10 C44 (ILDS C44.L21) ICD-9 173 ICD-O: M8090/3-8093/3 OMIM 605462 DiseasesDB 1264 MedlinePlus 000824 eMedicine med/214 MeSH D002280
Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a basal-cell cancer within their lifetime. In 80 percent of all cases, basal-cell cancers are found on the head and neck. There appears to be an increase in the incidence of basal-cell cancer of the trunk (torso) in recent years.
- Nodular basal-cell carcinoma (Classic basal-cell carcinoma)
- Cystic basal-cell carcinoma
- Cicatricial basal-cell carcinoma (Morpheaform basal-cell carcinoma, Morphoeic basal-cell carcinoma)
- Infiltrative basal-cell carcinoma
- Micronodular basal-cell carcinoma
- Superficial basal-cell carcinoma (Superficial multicentric basal-cell carcinoma)
- Pigmented basal-cell carcinoma
- Rodent ulcer (Jacobi ulcer)
- Fibroepithelioma of Pinkus
- Polypoid basal-cell carcinoma
- Pore-like basal-cell carcinoma
- Aberrant basal-cell carcinoma
For simplicity, one can also divide basal-cell carcinoma into 3 groups, based on location and difficulty of therapy:
- Superficial basal-cell carcinoma, or some might consider to be equivalent to "in-situ". Very responsive to topical chemotherapy such as Aldara, or Fluorouracil. It is the only type of basal-cell cancer that can be effectively treated with topical chemotherapy.
- Infiltrative basal-cell carcinoma, which often encompasses morpheaform and micronodular basal-cell cancer. More difficult to treat with conservative treatment methods such as electrodessiccation and currettage, or with currettage alone.
- Nodular basal-cell carcinoma, which essentially includes most of the remaining categories of basal-cell cancer. It is not unusual to encounter morphologic features of several variants of basal-cell cancer in the same tumor.
- Nevoid basal-cell carcinoma syndrome
Signs and symptoms
Patients present with a shiny, pearly nodule. However, superficial basal-cell cancer can present as a red patch like eczema. Infiltrative or morpheaform basal-cell cancers can present as a skin thickening or scar tissue – making diagnosis difficult without using tactile sensation and a skin biopsy. It is often difficult to distinguish basal-cell cancer from acne scar, actinic elastosis, and recent cryodestruction inflammation.
About two thirds of basal-cell carcinomas occur on sun-exposed areas of the body. One-third occur on areas of the body that are not exposed to sunlight, emphasizing the genetic susceptibility of basal-cell cancer patients.
To diagnose basal-cell carcinomas, a skin biopsy is taken for pathological study. The most common method is a shave biopsy under local anesthesia. Most nodular basal-cell cancers can be diagnosed clinically; however, other variants can be very difficult to distinguish from benign lesions such as intradermal nevus, sebaceomas, fibrous papules, early acne scars, and hypertrophic scarring.
Basal-cell carcinomas develop in the basal cell layer of the skin. Sun light exposure leads to the formation of thymine dimers, a form of DNA damage. While DNA repair removes most UV-induced damage, not all crosslinks are excised. There is, therefore, cumulative DNA damage leading to mutations. Apart from the mutagenesis, sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells.
Basal-cell carcinoma also develops as a result of Basal-Cell Nevus Syndrome, or Gorlin Syndrome, which is also characterized by keratocystic odontogenic tumors of the jaw, palmar or plantar (sole of the foot) pits, calcification of the falx cerebri (in the center line of the brain) and rib abnormalities. The cause of the syndrome is a mutation in the PTCH1 tumor-suppressor gene at chromosome 9q22.3, which inhibits the hedgehog signaling pathway. A mutation in the SMO gene, which is also on the hedgehog pathway, also causes basal-cell carcinoma.
Basal-cell carcinoma is the most common skin cancer. It occurs mainly in fair-skinned patients with a family history of this cancer. Sunlight is a factor in about two-thirds of these cancers; therefore, doctors recommend sun screens with at least SPF 30. One-third occur in non-sun-exposed areas.
The use of a chemotherapeutic agent such as 5-Fluorouracil or Imiquimod, can prevent development of skin cancer. It is usually recommended to individuals with extensive sun damage, history of multiple skin cancers, or precancerous growths. It is often repeated every 2 to 3 years to further decrease the risk of skin cancer.
The following methods are employed in the treatment of basal-cell carcinoma (BCC):
- Standard surgical excision with either frozen section histology, or paraffin embedded fixed tissue pathology. This is the preferred method for removal of most BCCs. The cure rate for this method, whether done by a plastic surgeon, family doctor, or dermatologist is totally dependent on the surgical margin. When standard surgical margin is applied (usually 4 mm or more), a high cure rate can be achieved with standard excision A dermatoscope can help an experienced surgeon accurately identify the visible tumour that the naked eye can not see. The narrower the free surgical margin (skin removed that is free of visible tumor) the higher the recurrence rate. A weakness with standard surgical excision is the high recurrence rate of basal-cell cancers of the face, especially around eyelids, nose, and facial structures. A diagram on page 33 of the NCCN publication demonstrate the area of high risk of recurrence as most the face with the exception of the central cheek and upper forehead. On the face, or on recurrent basal-cell cancer after previous surgery, special surgical margin controlled processing (CCPDMA - complete circumferential peripheral and deep margin assessment) using frozen section histology (Mohs surgery is one of the methods) is required. With surgical margin controlled frozen section histology, a surgeon can achieve a high cure rate and low recurrence rate on the same day of the excision. However, most standard excisions done in a plastic surgeon or dermatologist's office are sent to an outside laboratory for standard bread loafing method of processing. This method has a high "false negative" rate due to the random sampling of the tumour. It is likely that less than 5% of the surgical margin is examined, as each slice of tissue is only 6 micrometres thick, about 3 to 4 serial slices are obtained per section, and only about 3 to 4 sections are obtained per specimen (see figure 2 of reference). Usually, the rule of thumb is if a 4 mm free surgical margin is obtained around a small tumor (less than 6mm), or a wider 6 mm free surgical margin is obtained around a larger tumor (greater than 6mm), the cure rate is very high - 95% or better. For cosmetic reasons, many doctors take only very small surgical margins 1–2 mm, especially when facial tumour is being removed. A pathology report from such a case indicating "margins free of residual tumour", often is inaccurate, and a high recurrence rate of up to 38% might occur. When in doubt, a patient should demand that either Mohs surgery or frozen section histology with either margin control (ccpdma) or thin serial bread-loafing is utilized when dealing with a tumour on the face. The pathologist processing the frozen section specimen should cut multiple sections through the block to minimize the false negative error rate. Or one should simply process the tissue utilizing a method approximating the Mohs method (described in most basic histopathology text books or described in this reference ) during frozen section processing. Unfortunately, these methods are difficult when applied to frozen sections; and is very tedious to process. When not utilizing frozen section, the surgeon might have to wait a week or more, before informing the patient if more tumour is left, or if the surgical margin is too narrow. And a second surgery must be performed to remove the residual or potential residual tumour once the surgeon inform the patient of the positive or narrow surgical margin on the surgical pathology report.
- Mohs surgery: Mohs surgery (or Mohs micrographic surgery) is an outpatient procedure in which the tumor is surgically excised and then immediately examined under a microscope. It is a form of pathology processing called CCPDMA. It is claimed to have the highest cure rate of 97% to 99.8% by some individuals[who?]. The base and edges are microscopically examined to verify sufficient margins before the surgical repair of the site. If the margins are insufficient, more is removed from the patient until the margins are sufficient. It is also used for squamous-cell carcinoma; however, the cure rate is not as high as Mohs surgery for basal-cell carcinoma.
- Chemotherapy: Some superficial cancers respond to local therapy with 5-fluorouracil, a chemotherapy agent. Topical treatment with 5% Imiquimod cream, with five applications per week for six weeks has a reported 70-90% success rate at reducing, even removing, the BCC [basal-cell carcinoma]. Both Imiquimod and 5-fluorouracil have received FDA approval for the treatment of superficial basal-cell carcinoma. Off label use of imiquimod on invasive basal-cell carcinoma has been reported. Imiquimod may be used prior to surgery in order to reduce the size of the carcinoma. One can expect a great deal of inflammation with this treatment. Chemotherapy often follows Mohs surgery to eliminate the residual superficial basal-cell carcinoma after the invasive portion is removed. Some advocate the use of imiquimod prior to Mohs surgery to remove the superficial component of the cancer Removing the residual superficial tumor with surgery alone can result in large and difficult to repair surgical defects. One often waits a month or more after surgery before starting the Imiquimod or 5-fluorouracil to make sure the surgical wound has adequately healed. Some individuals[who?] advocate the use of curettage (see EDC below) first, then followed by chemotherapy. These experimental procedure likely will result in better cure rate than one alone, but are not standard care.
- Immunotherapy: Immunotherapy research suggests that treatment using Euphorbia peplus, a common garden weed, may be effective. Australian biopharmaceutical company Peplin is developing this as topical treatment for BCC. Imiquimod or Aldara is an immunotherapy but is listed here under chemotherapy.
- Radiation: Radiation therapy is appropriate for all forms of BCC as adequate doses will eradicate the disease. Radiation therapy can be delivered either as external beam radiotherapy or as brachytherapy (internal radiotherapy). Although radiotherapy is generally used in older patients who are not candidates for surgery, it is also used in cases where surgical excision will be disfiguring or difficult to reconstruct (especially on the tip of the nose, and the nostril rims). Radiation treatment often takes as few as 5 visits to as many as 25 visits for radiation therapy. Usually, the more visits scheduled for therapy, the less complication or damage is done to the normal tissue supporting the tumor. Radiotherapy can also be useful if surgical excision has been done incompletely or if the pathology report following surgery suggests a high risk of recurrence, for example if nerve involvement has been demonstrated. Cure rate can be as high as 95% for small tumor, or as low as 80% for large tumors. Usually, recurrent tumors after radiation are treated with surgery, and not with radiation. Further radiation treatment will further damage normal tissue, and the tumor might be resistant to further radiation.
- Photodynamic therapy: Photodynamic therapy is a new modality for treatment of basal-cell carcinoma, which is administrated by application of photosensitizers to the target area. When these molecules are activated by light, they become toxic, therefore destroy the target cells. Methyl aminolevulinate is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types.
- Cryosurgery: Cryosurgery is an old modality for the treatment of many skin cancers. When accurately utilized with a temperature probe and cryotherapy instruments, it can result in very good cure rate. Disadvantages include lack of margin control, tissue necrosis, over or under treatment of the tumor, and long recovery time. Overall, there are sufficient data to consider cryosurgery as a reasonable treatment for BCC. There are no good studies, however, comparing cryosurgery with other modalities, particularly with Mohs surgery, excision, or electrodesiccation and curretage so that no conclusion can be made whether cryosurgery is as efficacious as other methods. Also, there is no evidence on whether curetting the lesions before cryosurgery affects the efficacy of treatment. Several textbooks are published on the therapy, and a few physicians still apply the treatment to selected patients.
- Electrodesiccation and curettage: or EDC is accomplished by using a round knife, or curette, to scrape away the soft cancer. The skin is then burned with an electric current. This further softens the skin, allowing for the knife to cut more deeply with the next layer of curettage. The cycle is repeated, with a safety margin of curettage of normal skin around the visible tumor. This cycle is repeated 3 to 5 times, and the free skin margin treated is usually 4 to 6 mm. Cure rate is very much user dependent and depends on the size and type of tumor. Infiltrative or morpheaform BCCs can be difficult to eradicate with EDC. Generally, this method is used on cosmetically unimportant areas like the trunk (torso). Some physicians believe that it is acceptable to utilize EDC on the face of elderly patients over the age of 70. However, with increasing life expectancy, such an objective criterion cannot be supported. The cure rate can be low or high, depending on the aggressiveness of the EDC and the free margin treated. Some advocate curettage alone without electrodesiccation, and with the same cure rate.
Treating surgeons will recommend one of these modalities as appropriate treatment depending on the tumour size, location, patient age, and other variables.
Prognosis is excellent if the appropriate method of treatment is used in early primary basal-cell cancers. Recurrent cancers are much harder to cure, with a higher recurrent rate with any methods of treatment. Although basal-cell carcinoma rarely metastasizes, it grows locally with invasion and destruction of local tissues. The cancer can impinge on vital structures like nerves and result in loss of sensation or loss of function or rarely death. The vast majority of cases can be successfully treated before serious complications occur. The recurrence rate for the above treatment options ranges from 50 percent to 1 percent or less.
Basal-cell cancer is the most common skin cancer. It is much more common in fair-skinned individuals with a family history of basal-cell cancer and increases in incidence closer to the equator or at higher altitude. According to Skin Cancer Foundation, there are approximately 800,000 new cases yearly in the United States alone. Up to 30% of caucasians develop basal-cell carcinomas in their lifetime. In Canada, the most common skin cancer is basal cell carcinoma (as much as one third of all cancer diagnoses), affecting 1 in 7 individuals over a lifetime. 
Most sporadic BCC arises in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. The development of multiple basal-cell cancer at an early age could be indicative of Nevoid basal-cell carcinoma syndrome.
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Diseases of the skin and appendages by morphology GrowthsPigmentedDermal and
PurpuraMacularthrombocytopenic purpura · actinic purpuraPapularIndurated
Glandular and epithelial neoplasms (ICD-O 8010-8589) Epithelium GlandsOther/multipleAdnexal and
skin appendage (8390-8429)Cystic, mucinous,
and serous (8440-8499)Cystic generalSerousDuctal, lobular,
and medullary (8500-8549)Lobular carcinoma in situ · Invasive lobular carcinomaAcinar cell (8550-8559)
OtherComplex epithelial (8560-8589)see also Template:Epithelium and epithelial tissue Tumors: Skin neoplasm, Epidermis (C44.L12–L38/D23.L53-83, 173/216) TumorBCCMicronodular basal cell carcinoma · Superficial basal cell carcinoma · Nodular basal cell carcinoma (Rodent ulcer) · Cystic basal cell carcinoma · Cicatricial basal cell carcinoma · Pigmented basal cell carcinoma · Aberrant basal cell carcinoma · Infiltrative basal cell carcinoma · Nevoid basal cell carcinoma syndrome · Polypoid basal cell carcinoma · Pore-like basal cell carcinoma · Fibroepithelioma of PinkusOther/ungroupedOtherMixed tumor (Malignant mixed tumor) Ungrouped
epidermal nevus: Epidermal nevus syndrome · Inflammatory linear verrucous epidermal nevus · Linear verrucous epidermal nevus · Pigmented hairy epidermal nevus syndrome · Systematized epidermal nevus · Schimmelpenning syndrome · Nevus comedonicus/Nevus comedonicus syndrome · Phakomatosis pigmentokeratoticabalanitis (Balanitis plasmacellularis, Pseudoepitheliomatous keratotic and micaceous balanitis) · Cutaneous horn
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