<!-- Definition and symptoms -->
Basal-cell carcinoma (BCC), also known as basal-cell cancer, basalioma, or rodent ulcer, is the most common type of skin cancer. Basal-cell cancer grows slowly and can damage the tissue around it, but it is unlikely to spread to distant areas or result in death.
<!-- Causes and prevention -->
Risk factors include exposure to ultraviolet light (UV), having lighter skin, radiation therapy, long-term exposure to arsenic, and poor immune-system function. Tanning beds have become another common source of ultraviolet radiation. Whether sunscreen affects the risk of basal-cell cancer remains unclear.
<!-- Diagnosis and treatment -->
Diagnosis often depends on skin examination, confirmed by tissue biopsy. Treatment is typically by surgical removal. In the rare cases in which distant spread has occurred, chemotherapy or targeted therapy may be used. Of skin cancers other than melanoma, about 80% are BCCs. In the United States, about 35% of White males and 25% of White females are affected by BCC at some point in their lives.
<gallery mode="packed" heights="180px" style="text-align:left">
image:Basal cell carcinoma.jpg|Basal cell carcinoma on the patient's back
Basal-cell Carcinoma.jpg|Basal-cell carcinoma (BCC)
File:Basal Cell Carcinoma Left Upper Back nodular and micronodular.jpg|BCC on the left upper back, nodular and micronodular, marked for biopsy
image:Dermoscopy_nodular_basal_cell_carcinoma.jpg|Dermoscopy showing telangiectatic vessels
</gallery>
Cause
Most BCCs occur on sun-exposed areas of the body.
Pathophysiology
right|thumb|200px|[[Micrograph of a basal-cell carcinoma, showing the characteristic histomorphologic features (peripheral palisading, myxoid stroma, artefactual clefting), H&E stain]]
Basal-cell carcinoma (BCC) is named after the basal cells that populate the lowest layer of the epidermis due to the histological appearance of the cancer cells under the microscope. Some are thought to develop from the folliculo–sebaceous–apocrine germinative cells known as trichoblasts. Trichoblastic carcinoma is a term used to describe a rare and potentially aggressive malignancy that is also thought to arise from trichoblasts and may resemble a benign trichoblastoma (differential diagnosis can be challenging). It has been suggested that lesions diagnosed as trichoblastic carcinoma may actually themselves be BCC.
Overexposure to the sun 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, so cumulative DNA damage can lead to mutations. Apart from the mutagenesis, overexposure to sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells. Studies of the role of DNA repair in susceptibility to sunlight-induced BCC indicated that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.
Basal-cell carcinomas can often occur in association with other lesions of the skin, such as actinic keratosis, seborrheic keratosis, and squamous-cell carcinoma. In a small proportion of cases, BCC 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 this syndrome is a mutation in the PTCH1 tumor suppressor gene located in chromosome 9q22.3, which inhibits the hedgehog signaling pathway. A mutation in the SMO gene, which is also on the hedgehog pathway, also causes BCC.
Diagnosis
thumb|Ulcerated BCC affecting the skin of the nose in an elderly individual
To diagnose basal-cell carcinomas, a skin biopsy is performed for histopathologic analysis. The most common method is a shave biopsy under local anesthesia. Most nodular BCCs can be diagnosed clinically; however, other variants can be challenging to distinguish from benign lesions such as intradermal naevus, sebaceomas, fibrous papules, early acne scars, and hypertrophic scarring. Exfoliative cytology methods have high sensitivity and specificity for confirming the diagnosis of BCC when clinical suspicion is high, but of unclear usefulness otherwise.
Characteristics
thumb|High-magnification micrograph of basal-cell carcinoma
Basal-cell carcinoma cells resemble epidermal basal cells and are usually well differentiated.
In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only BCC cells.
Main classes
Basal-cell carcinoma can broadly be divided into three groups, based on the growth patterns.
- Superficial basal-cell carcinoma, formerly referred to as in-situ basal-cell carcinoma, is characterized by a superficial proliferation of neoplastic basal-cells. This tumor is generally responsive to topical chemotherapy, such as imiquimod, or fluorouracil, although surgical treatment is better able to ensure complete removal and confirm that there is not an underlying more aggressive subtype that was not sampled in the initial biopsy.
- Infiltrative basal-cell carcinoma, which also encompasses morpheaform and micronodular basal-cell cancer, is more difficult to treat with conservative methods, given its tendency to penetrate into deeper layers of the skin.
- Nodular basal-cell carcinoma includes most of the remaining categories of basal-cell cancer. It is not unusual to encounter heterogeneous morphologic features within the same tumor.
Nodular basal-cell carcinoma
thumb|Basal-cell carcinoma with nodular pattern
Nodular basal-cell carcinoma (also known as "classic basal-cell carcinoma") accounts for 50% of all BCC. Such clefts are caused by shrinkage of mucin during tissue fixation and staining. Central necrosis with eosinophilic, granular features may also be present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may also be present, especially in long-standing lesions.
{|class="wikitable"
! Type !! Histopathology !! Other characteristics !! Image
|-
| Cystic basal-cell carcinoma
| || Morphologically characterized by dome-shaped, blue-gray cystic nodules. || Aggressive || Most commonly occurs on the lower back.
{|class="wikitable"
! Low-level aggressive pattern !! Moderately aggressive pattern !! Highly aggressive pattern
|-
|
<gallery>
File:Low-level aggressive basal-cell carcinoma.jpg|Cohesive nodular
File:Micrograph of superficial basal-cell carcinoma.jpg|Superficial
File:Micrograph of basal-cell carcinoma with fibroepitheliomatous pattern.jpg|Fibroepitheliomatous pattern (anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma)
</gallery>
|
<gallery>
File:Moderately aggressive basal-cell carcinoma.jpg|Moderate cohesion
</gallery>
|
<gallery>
File:Morpheaform basal-cell carcinoma.jpg|Narrow strands and nests of basaloid cells. "Cicatricial" or "morphoeic" pattern.
</gallery>
|}
Differential diagnoses
{|class="wikitable"
|+Main histological differential diagnoses of basal cell carcinoma: CEA+, EMA+ || <gallery mode="packed" heights="135">
File:Micrograph of microcystic adnexal carcinoma - superficial follicular keratin-filled cysts.jpg
File:Micrograph of microcystic adnexal carcinoma - infiltrative aggregates.jpg
</gallery>
|-
| Trichoepithelioma || Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation, and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemia antigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Receptor- (AR-) || 190px
|-
| Merkel cell carcinoma || Cells arranged in a diffuse, trabecular, and/or nested pattern, involving also the subcutis. Mouse Anti-Cytokeratin (CAM) 5.2+, CK20+, S100-, human leukocyte common antigen- ( LCA-), thyroid transcription factor 1- (TTF1-) || 190px
|}
Radicality
[[File:BCC with squamous cell metaplasia with HE and BerEP4 staining.jpg|thumb|300px|Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having BCC with squamous cell metaplasia. Only BCC cells are stained with BerEP4. The review did ultimately state that the certainty of these results was low, so future evidence could very well alter this conclusion. One-third occur in non-sun-exposed areas; thus, the pathogenesis is more complex than UV exposure as the cause. It is often repeated every 2 to 3 years to decrease the risk of skin cancer further.
Treatment
The following methods are employed in the treatment of basal-cell carcinoma (BCC):
Standard surgical excision
thumb|right|Basal cell carcinoma, right cheek, marked for biopsy
Surgery to remove the basal-cell carcinoma affected area and the surrounding skin is thought to be the most effective treatment. A disadvantage with standard surgical excision is a reported higher recurrence rate of basal-cell cancers of the face, especially around the eyelids, nose, and facial structures. There is no clear approach, nor clear research comparing the effectiveness of Mohs micrographic surgery versus surgical excision for BCC of the eye.
For basal cell carcinoma excisions on the lower lip, the wound can be covered with a keystone flap. A keystone flap is achieved by creating a flap below the defect and pulling it superiorly to cover the wound. This can be performed if there is enough skin laxity to cover the defect and adequate blood supply to the flap.
Mohs surgery
For many new (primary) and all recurrent forms of basal cell carcinoma after previous surgery, especially on the head, neck, hands, feet, genitalia, and anterior legs (shins), Mohs surgery should be considered.
Mohs surgery (or Mohs micrographic surgery) is an outpatient procedure, developed by Frederic E. Mohs in the 1930s, usually with cure rates higher than for other surgical and non-surgical treatments. With this method, 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.
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 a very good cure rate. Disadvantages include a lack of margin control, tissue necrosis, over- or under-treatment of the tumor, and long recovery time. Overall, there is 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 curettage, so 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
Electrodesiccation and curettage (EDC, also known as curettage and cautery, simply curettage) 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 also 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 vary, depending on the aggressiveness of the EDC and the free margin treated. Some advocate curettage alone without electrodesiccation, and with the same cure rate.
Chemotherapy
Some superficial cancers respond to local therapy with 5-fluorouracil, a chemotherapy agent. 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. 5-fluorouracil has received FDA approval.
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 immunotherapy or chemotherapy to make sure the surgical wound has adequately healed. Some people advocate the use of curettage (see EDC below) first, followed by chemotherapy. These experimental procedures are not standard care.
Immunotherapy
This technique uses the body's immune system to kill cancer cells. Improvement of the immune system works its way up to the cancerous cells and treats the skin cancer.
Topical treatment with 5% Imiquimod cream (IMQ), with five applications per week for six weeks, has a reported 70–90% success rate at reducing, even removing, the BCC [basal-cell carcinoma]. Imiquimod has received FDA approval, and topical IMQ is approved by the European Medicines Agency for the treatment of small superficial basal-cell carcinoma.
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.
Radiation
Radiation therapy can be delivered either as external beam radiotherapy or as brachytherapy (mostly 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 with external radiation often takes as few as 5 visits to as many as 25 visits. 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. The cure rate can be as high as 95% for small tumors or as low as 80% for large tumors. A variation of an external brachytherapy is the epidermal radioisotope therapy (e.g., with <sup>188</sup>Re in the form of the Rhenium-SCT). It is used in accordance with the general indications for brachytherapy and especially complex localisations or structures (e.g., earlobe) as well as the genitals.
Usually, recurrent tumors after radiation are treated with surgery, not with radiation. Further radiation treatment will further damage normal tissue, and the tumor might be resistant to further radiation. Radiation therapy may be contraindicated for the treatment of nevoid basal-cell carcinoma syndrome. A 2008 study reported that radiation therapy is appropriate for primary BCCs and recurrent BCCs, but not for BCCs that have recurred following previous radiation treatment. A 2008 study reported that PDT was a good treatment option for primary superficial BCCs and reasonable for primary low-risk nodular BCCs, but was a "relatively poor" option for high-risk lesions. When completely excised, the recurrence rate for basal-cell carcinoma is relatively low. However, when recurrence occurs among surgically treated basal-cell carcinomas of the face, there is a strong correlation with tumor thickness. There are approximately 800,000 new cases yearly in the United States alone. Up to 30% of white people 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. This tumor accounts for approximately 70% of non-melanoma skin cancers. In 80 percent of all cases, basal-cell carcinoma affects the head or neck skin.