Basal cell carcinoma

Published on 19/03/2015 by admin

Filed under Dermatology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 1 (1 votes)

This article have been viewed 2660 times

[level-membership-for-dermatology-category]

Basal cell carcinoma

James M. Spencer and Brooke M. Walls

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Basal cell carcinoma (BCC) is a slow-growing malignancy originating in the epidermis. It most commonly arises in areas chronically exposed to UV light, especially the head and neck. Although it is very rare for BCC to metastasize, it can produce significant local tissue destruction, including cartilage and bony invasion.

Management strategy

Basal cell carcinoma slowly but relentlessly grows larger and deeper, and therefore therapeutic intervention is geared towards complete eradication of all malignant cells. Local recurrence is the consequence of inadequate therapy. Complete eradication is especially important because recurrent tumors are often larger and more aggressive than the original, incompletely treated primary tumor. Although complete eradication is the primary goal, the therapy chosen should achieve this with the maximal preservation of function and the optimal cosmetic result. Most often, therapy uses destructive techniques such as cryotherapy or curettage and electrodesiccation (C&D); more complex tumors may be treated by excisional surgery, Mohs surgery, or radiation therapy. The decision about which therapy to use is best made by considering four factors: tumor size; location; histology; and history (recurrent vs primary). When assessing a tumor, the clinician may wish to consider each of these four factors and decide whether the patient is high risk or low risk for each, to determine whether to use a simple or complex therapeutic strategy.

Most BCCs are discovered as primary tumors when they are still less than 1 cm in diameter. Generally tumors smaller than 1 cm on the face and 2 cm on the body are low risk.

Histologic growth pattern is a separate risk factor. The cytology of BCC does not vary: that is, all BCCs have well-differentiated, relatively monomorphic cell populations, and these tumors are not graded the way other malignancies are. However, the pattern of growth is variable and makes a large difference in choosing therapy. One must consider whether the tumor has a circumscribed or a diffuse growth pattern. Basal cell carcinoma most typically exhibits a circumscribed, cohesive growth pattern known as nodular. Nodular BCCs may show partial differentiation towards other structures, such as cystic or keratotic, but these variants are without therapeutic significance because the growth pattern is still nodular. Morpheaform, micronodular, infiltrating and superficial BCCs are all variants that exhibit a diffuse growth pattern. These lesions are more likely to recur as a result of subclinical extension or more aggressive tumor behavior, or both. Unfortunately, all too often biopsy reports come back to the clinician and simply state ‘BCC’, with no information about the growth pattern. Inadequately treated nodular BCC often recurs with a more aggressive diffuse growth pattern, such as infiltrating or micronodular.

Location is also an important variable to consider when choosing which therapy to use. Basal cell carcinoma tends to occur in chronically sun-exposed sites, especially the head and neck. Approximately 80% occur on the head and neck, and fully 25% occur on the nose. The central portion of the face, which has the highest incidence of BCC, contains the eyes, nose, and mouth, structures of functional and cosmetic importance highly vulnerable to the destructive effects of BCC. These same structures are also highly vulnerable to the destructive effects of therapy directed against BCC. The center of the face extending onto the area around the ears defines a roughly H-shaped area known as the H zone. Tumors in this zone have the highest recurrence rate and thus deserve special therapeutic attention. This zone also contains the most vulnerable structures and has the highest rate of BCC occurrence. Tumors near the ear canal, in the H zone, are of special concern. Extension down the ear canal provides the tumor with access to the brain and other intracranial structures, and when there is evidence of ear canal invasion particularly aggressive therapy is warranted.

Lastly, tumor history is important to consider. Recurrent tumors are more difficult to treat than primary tumors and require more aggressive methods.

When confronted with a BCC, the clinician may wish to consider these four variables in the context of the individual patient. The patient’s overall medical status, medical history, and age may influence the therapeutic decision making.

Specific investigations

An adequate biopsy is critical in assessing the tumor. The tumor growth pattern is important information that is impossible to determine if only a superficial fragment is submitted to the laboratory. Deep shave, punch, incisional or excisional biopsy can all give sufficient dermis for such an evaluation. Because metastasis is so rare, no further evaluation is warranted.

A number of non-invasive imaging technologies are being investigated to delineate tumor depth and extent preoperatively and thus guide treatment. These include confocal microscopy, infrared spectroscopy, and ultrasound, but these all remain experimental and are not part of routine care.

Rarely, a BCC may have been neglected and reached a size such that direct bony invasion has occurred. If this is strongly suspected, a preoperative CT scan should be considered.

The possibility that patients with a BCC have an increased risk of developing subsequent internal malignancies has been suggested over the years, and remains controversial. At present there is no recommendation for extraordinary evaluation for internal malignancies beyond routine medical care in patients with a history of BCC.

Basal cell carcinoma and risk of subsequent malignancies: a cancer registry-based study in southwest England.

Bower CP, Lear JT, Bygrave S, Etherington D, Harvey I, Archer CB. J Am Acad Dermatol 2000; 42: 988–91.

A cohort of 13 961 patients diagnosed with BCC between 1981 and 1988 were followed for additional malignancies. There was a significant increased risk of subsequent melanoma, but no increased risk for internal malignancies.

Further complicating the relationship of BCC to other cancers is the argument that vitamin D provides chemoprevention for some visceral cancers. Specifically, it has been theorized that elevated levels of vitamin D lower the incidence of a variety of tumors, including breast, colon, and prostate cancers. As vitamin D is manufactured in the skin following exposure to UVB, it has been suggested that those with high UVB exposure should have a higher incidence of BCC but a lower incidence of breast, colon, and prostate cancers, among others.

First-Line therapies

imageCurettage and electrodesiccation B
imageCryosurgery B
imageExcisional surgery B
imageMohs micrographic surgery B

A systematic review of treatment modalities for primary basal cell carcinomas.

Thissen MR, Neumann MH, Schouten LJ. Arch Dermatol 1999; 135: 1177–83.

Meta-analysis of published studies evaluating therapeutic methods for treating BCC. Inclusion criteria were prospective studies of at least 50 patients with primary BCC and at least 5 years’ follow-up. Four studies of cryosurgery filled these criteria, with recurrence rates ranging from 0% to 20.4%.

Several large retrospective reports indicate a greater than 95% cure rate with cryotherapy. However, once again the size, histology, location, and history of the tumors are not defined, and hence such reports are difficult to interpret in a clinically useful way. The authors of such series generally recommend two freeze–thaw cycles to maximize cell death and the use of a cryoprobe to assess tissue temperature achieved: −50°C is generally regarded as sufficiently cytotoxic.

Surgical excision vs Mohs’ micrographic surgery for basal-cell carcinoma of the face: randomized controlled trial.

Smeets NW, Krekels GA, Ostertag JU, Essers BA, Dirksen CD, Nieman FH, et al. Lancet 2004; 364: 1766–72.

A randomized, prospective trial comparing Mohs surgery with conventional surgical excision has been initiated. In this preliminary report, 408 primary and 204 recurrent facial BCCs were randomized to surgical excision with 3 mm margins or Mohs surgery. At 18-month follow-up the recurrence rate of primary BCC in the surgical excision group available for analysis was 2.9% (5/171) and 1.9% (3/160) in the Mohs group. The patients with recurrent tumor were seen at 30 months’ follow-up, and the recurrence rate of patients actually seen for follow-up was 3.2% (3/93) for the surgical excision group and 0% (0/95) for the Mohs group.

This preliminary report gives the suggestion that Mohs surgery has a lower recurrence rate than conventional surgical excision, but does not reach statistical significance. It is the intention of the authors to continue this study to 5 years of follow-up, at which time any differences may be more obvious.

Second-Line therapies

imageRadiation therapy B

Therapeutic ionizing radiation and the incidence of basal cell carcinoma and squamous cell carcinoma.

The New Hampshire Skin Cancer Study Group. Lichter MD, Karagas MR, Mott LA, Spencer SK, Stukel TA, Greenberg ER. Arch Dermatol 2000; 136: 1007–11.

There is a statistically significant increased risk of the development of BCC in the exposure window following therapeutic RT. The development of subsequent tumors is a significant possible side effect.

Radiation therapy is an effective, albeit expensive and time-consuming option for patients unable or unwilling to undergo surgery. Generally, 3000–5000 cGy are given in six to 20 fractionated doses, so therapy may take weeks. Cure rates have repeatedly been reported to be in excess of 90%. BCCs with perineural invasion have a very high local recurrence rate, and postoperative radiation is a wise precaution.

Third-Line therapies

imageIntralesional interferon B
imageRetinoids D
imageTopical imiquimod A
imagePhotodynamic therapy A
imageTopical 5-fluorouracil A
imageCO2 laser D
imagePEG–interleukin 2 D
imageNSAIDs D
imageIngenol mebutate D
imageVismodegib A
imageIntralesional interleukin D
imageSystemic chemotherapy D

Open study of the efficacy and mechanism of action of topical imiquimod in basal cell carcinoma.

Vidal D, Matias-Guiu X, Alomar A. Clin Exp Dermatol 2004; 29: 518–25.

Fifty-five BCCs measuring more than 8 mm in diameter with superficial, nodular, or infiltrative histologic growth patterns were treated daily, either three times a week for 8 weeks or five times a week for 5 weeks. Punch biopsies were taken 6 weeks after therapy, and patients were followed clinically for 2 years: 4/4 (100%) of superficial BCCs, 7/8 (88%) of nodular BCCs, and 30/43 (70%) of infiltrating BCCs were tumor free following therapy.

This product upregulates interferons α and γ, and interleukin 12, among other cytokines. It seems to be reasonably effective for superficial BCCs, but less so for other histologic growth patterns.

Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two year results evaluating tumor response and cosmetic outcomes.

Lui H, Hobbs L, Tope WD, Lee PK, Elmets C, Provost N, et al. Arch Dermatol 2004; 140: 26–32.

Fifty-four patients with 421 non-melanoma skin cancers, including superficial BCC, nodular BCC, and SCC in situ, were treated with intravenous verteporfin followed by varying doses of red light. Treated areas were biopsied 6 months after treatment, and patients were followed clinically for 2 years. At the highest light dose, 93% of treated tumors were clear on biopsy, and 95% were clinically clear at 2-year follow-up.

Like Photofrin, verteporfin is an intravenous medication but has the advantage that patients are photosensitive for only 3 to 5 days.

Topical photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) and its methylated derivative (mALA) has become more popular, and is commonly used in Europe. Surgical excision remains the gold standard to which other therapies must be compared. Comparison of different therapeutic modalities has been hard because few randomized prospective comparative trials have been performed. One such trial with 5-year follow-up has been completed comparing PDT with mALA to conventional surgical excision.

Nonsteroidal anti-inflammatory drugs and the risk of skin cancer: a population-based case-control study.

Johannesdottir SA, Chang ET, Mehnert F, Schmidt M, Olesen AB, Sorensen HT. Cancer 2012; [Epub, www.wileyonlinelibrary.com; accessed 6/25/2012].

A total of 13 316 BCCs in northern Denmark were identified and matched with 10 population controls each based on age, gender, and county of residence. The use of aspirin, non-selective NSAIDs, or selective COX-2 inhibitors was ascertained through a prescription database. Ever-use was not associated with a reduced incidence of BCC; however, long-term and/or high-intensity use was associated with a 10% to 17% reduced risk of BCC. They also observed an inverse relationship between acetaminophen use and the risk of BCC at sites other than the head and neck in high-intensity or long-term users. There are many limitations to this study, including the data relied on dispensed prescriptions, which may not reflect actual use. As well, there are no data on lifestyle of the cases.

Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.

Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. N Engl J Med 2009; 361: 1164–72.

Inhibition of smoothen to halted the progression of tumorigenesis in 33 patients with inoperable BCCs. Phase I trial in which 18 patients with metastatic disease and 15 patients with locally advanced BCC were treated with either 150 mg/day (n = 17), 270 mg/day (n = 15), or 540 mg/day (n = 1). Eighteen patients had a response, 11 had stable disease, and four had progression of their disease. Eighteen patients showed a response to the drug; two CR and 16 PR. In the other patients, 15 had stable disease while four had progression of disease. While advanced or metastatic BCC is rare outside of those with basal cell nevus syndrome, study of the hedgehog (Hh) pathway and PTCH genetic mutations has led to a greater understanding of basal cell carcinogenesis. Adverse events were common with eight reported grade 3 events including fatigue, muscle spasms, and atrial fibrillation and one grade 4 event – asymptomatic hyponatremia.

The first oral hedgehog inhibitor, vismodegib, is approved in a dose of 150 mg daily.

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Basal cell carcinoma

James M. Spencer and Brooke M. Walls

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Basal cell carcinoma (BCC) is a slow-growing malignancy originating in the epidermis. It most commonly arises in areas chronically exposed to UV light, especially the head and neck. Although it is very rare for BCC to metastasize, it can produce significant local tissue destruction, including cartilage and bony invasion.

Management strategy

Basal cell carcinoma slowly but relentlessly grows larger and deeper, and therefore therapeutic intervention is geared towards complete eradication of all malignant cells. Local recurrence is the consequence of inadequate therapy. Complete eradication is especially important because recurrent tumors are often larger and more aggressive than the original, incompletely treated primary tumor. Although complete eradication is the primary goal, the therapy chosen should achieve this with the maximal preservation of function and the optimal cosmetic result. Most often, therapy uses destructive techniques such as cryotherapy or curettage and electrodesiccation (C&D); more complex tumors may be treated by excisional surgery, Mohs surgery, or radiation therapy. The decision about which therapy to use is best made by considering four factors: tumor size; location; histology; and history (recurrent vs primary). When assessing a tumor, the clinician may wish to consider each of these four factors and decide whether the patient is high risk or low risk for each, to determine whether to use a simple or complex therapeutic strategy.

Most BCCs are discovered as primary tumors when they are still less than 1 cm in diameter. Generally tumors smaller than 1 cm on the face and 2 cm on the body are low risk.

Histologic growth pattern is a separate risk factor. The cytology of BCC does not vary: that is, all BCCs have well-differentiated, relatively monomorphic cell populations, and these tumors are not graded the way other malignancies are. However, the pattern of growth is variable and makes a large difference in choosing therapy. One must consider whether the tumor has a circumscribed or a diffuse growth pattern. Basal cell carcinoma most typically exhibits a circumscribed, cohesive growth pattern known as nodular. Nodular BCCs may show partial differentiation towards other structures, such as cystic or keratotic, but these variants are without therapeutic significance because the growth pattern is still nodular. Morpheaform, micronodular, infiltrating and superficial BCCs are all variants that exhibit a diffuse growth pattern. These lesions are more likely to recur as a result of subclinical extension or more aggressive tumor behavior, or both. Unfortunately, all too often biopsy reports come back to the clinician and simply state ‘BCC’, with no information about the growth pattern. Inadequately treated nodular BCC often recurs with a more aggressive diffuse growth pattern, such as infiltrating or micronodular.

Location is also an important variable to consider when choosing which therapy to use. Basal cell carcinoma tends to occur in chronically sun-exposed sites, especially the head and neck. Approximately 80% occur on the head and neck, and fully 25% occur on the nose. The central portion of the face, which has the highest incidence of BCC, contains the eyes, nose, and mouth, structures of functional and cosmetic importance highly vulnerable to the destructive effects of BCC. These same structures are also highly vulnerable to the destructive effects of therapy directed against BCC. The center of the face extending onto the area around the ears defines a roughly H-shaped area known as the H zone. Tumors in this zone have the highest recurrence rate and thus deserve special therapeutic attention. This zone also contains the most vulnerable structures and has the highest rate of BCC occurrence. Tumors near the ear canal, in the H zone, are of special concern. Extension down the ear canal provides the tumor with access to the brain and other intracranial structures, and when there is evidence of ear canal invasion particularly aggressive therapy is warranted.

Lastly, tumor history is important to consider. Recurrent tumors are more difficult to treat than primary tumors and require more aggressive methods.

When confronted with a BCC, the clinician may wish to consider these four variables in the context of the individual patient. The patient’s overall medical status, medical history, and age may influence the therapeutic decision making.

Specific investigations

An adequate biopsy is critical in assessing the tumor. The tumor growth pattern is important information that is impossible to determine if only a superficial fragment is submitted to the laboratory. Deep shave, punch, incisional or excisional biopsy can all give sufficient dermis for such an evaluation. Because metastasis is so rare, no further evaluation is warranted.

A number of non-invasive imaging technologies are being investigated to delineate tumor depth and extent preoperatively and thus guide treatment. These include confocal microscopy, infrared spectroscopy, and ultrasound, but these all remain experimental and are not part of routine care.

Rarely, a BCC may have been neglected and reached a size such that direct bony invasion has occurred. If this is strongly suspected, a preoperative CT scan should be considered.

The possibility that patients with a BCC have an increased risk of developing subsequent internal malignancies has been suggested over the years, and remains controversial. At present there is no recommendation for extraordinary evaluation for internal malignancies beyond routine medical care in patients with a history of BCC.

Basal cell carcinoma and risk of subsequent malignancies: a cancer registry-based study in southwest England.

Bower CP, Lear JT, Bygrave S, Etherington D, Harvey I, Archer CB. J Am Acad Dermatol 2000; 42: 988–91.

A cohort of 13 961 patients diagnosed with BCC between 1981 and 1988 were followed for additional malignancies. There was a significant increased risk of subsequent melanoma, but no increased risk for internal malignancies.

Further complicating the relationship of BCC to other cancers is the argument that vitamin D provides chemoprevention for some visceral cancers. Specifically, it has been theorized that elevated levels of vitamin D lower the incidence of a variety of tumors, including breast, colon, and prostate cancers. As vitamin D is manufactured in the skin following exposure to UVB, it has been suggested that those with high UVB exposure should have a higher incidence of BCC but a lower incidence of breast, colon, and prostate cancers, among others.

First-Line therapies

imageCurettage and electrodesiccation B
imageCryosurgery B
imageExcisional surgery B
imageMohs micrographic surgery B

Cryosurgery of basal cell carcinoma: a study of 358 patients.
Buy Membership for Dermatology Category to continue reading. Learn more here

[/not-level-membership-for-dermatology-category]