AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

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• Clinical
• Differentials
• Workup
• Treatment
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• Follow-up
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Background

Basal cell carcinoma (BCC) is the most common malignancy in humans. It typically occurs in areas of chronic sun exposure. BCC is usually slow growing and rarely metastasizes, but it can cause clinically significant local destruction and disfigurement if neglected or inadequately treated. Prognosis is excellent with proper therapy.

Pathophysiology

Many believe that BCCs arise from pluripotential cells in the basal layer of the epidermis or follicular structures. These cells form continuously during life and can form hair, sebaceous glands, and apocrine glands. Tumors usually arise from the epidermis and occasionally arise from the outer root sheath of a hair follicle, specifically from hair follicle stem cells residing just below the sebaceous gland duct in an area called the bulge.

The patched/hedgehog intracellular signaling pathway plays a role in both sporadic BCCs and in nevoid BCC syndrome (Gorlin syndrome). This pathway influences differentiation of a variety of tissues during fetal development. After embryogenesis, it continues to function in regulation of cell growth and differentiation. Loss of inhibition of this pathway is associated with human malignancy, including BCC.

The hedgehog gene encodes an extracellular protein that binds to a cell membrane receptor complex to start a cascade of cellular events leading to cell proliferation. Of the 3 known human homologs, Sonic hedgehog (SHH) protein is the most relevant to BCC. Patched (PTCH) is a protein that is the ligand-binding component of the hedgehog receptor complex in the cell membrane. The other protein member of the receptor complex, smoothened (SMO), is responsible for transducing hedgehog signaling to downstream genes.^{1, 2}

When SHH is present, it binds to PTCH, which then releases and activates SMO. SMO signaling is transduced to the nucleus via Gli. When SHH is absent, PTCH binds to and inhibits SMO. Mutations in the PTCH gene prevent it from binding to SMO, simulating the presence of SHH. The unbound SMO and downstream Gli are constitutively activated, thereby allowing hedgehog signaling to proceed unimpeded. The same pathway may also be activated via mutations in the SMO gene, which also allows unregulated signaling of tumor growth. How these defects cause tumorigenesis is not fully understood, but most BCCs have abnormalities in either PTCH or SMO genes. Some even consider defects in the hedgehog pathway to be requirements for BCC development.

UV-induced mutations in the TP53 tumor-suppressor gene, which resides on band 17p13.1, have been found in some cases of BCC.³ Activated BCL2 (an antiapoptosis proto-oncogene) also is commonly found in BCCs and may be detected immunohistochemically.

Frequency

United States

The annual incidence is 900,000 cases (550,000 in men, 350,000 in women). The age-adjusted incidence per 100,000 white individuals is 475 cases in men and 250 cases in women. The estimated lifetime risk of BCC in the white population is 33-39% in men and 23-28% in women.

Mortality/Morbidity

BCC can cause clinically significant morbidity if allowed to progress. Because this cancer most commonly affects the head and neck, cosmetic disfigurement is not uncommon. Loss of vision or the eye may occur with orbital involvement. Perineural spread can result in loss of nerve function and in deep and extensive invasion of the tumor. These neoplasms are often friable and prone to ulceration; thus, they provide a nidus for infection. Death from BCC is extremely rare.

Race

BCC is generally a disorder of white individuals, especially those with fair skin. It is rare in dark-skinned individuals.

Sex

The male-to-female ratio is approximately 3:2.

Age

BCC most commonly occurs in adulthood, especially in elderly persons.

CLINICAL

Section 3 of 10  

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• Workup
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History

Patients often present with a nonhealing sore of varying duration. The lesions are typically seen on the face, ears, scalp, neck, or upper trunk. Mild trauma, such as face washing or drying with a towel, initially may cause bleeding. A history of chronic recreational or occupational sun exposure is commonly elicited. Intense sun exposure often occurred in childhood or young adulthood.

Physical

Several clinical and histologic subtypes of BCC may exhibit different patterns of behavior. Recognizing the various types is important because aggressive therapy is often necessary for variants such as micronodular, infiltrating, or morpheaform BCC. When one examines possible skin cancers, the best plan is to use good lighting and magnification. The affected skin should be stretched, squeezed, and palpated to best estimate the size and depth of the tumor. Oblique illumination of the tumor can highlight surface changes, such as a rolled border.

• Nodular BCC: This is the most common variety of BCC. Nodular BCCs most commonly occur on the head, neck, and upper back. They may have some of the following features:
• • Waxy papules with central depression (see Media File 2)
  • Pearly appearance
  • Erosion or ulceration
  • Bleeding
  • Crusting
  • Rolled (raised) border (see Media Files 4-5)
  • Translucency
  • Telangiectases over the surface
  • History of bleeding with minor trauma
• Pigmented BCC: In addition to features seen in lesions of nodular BCC, lesions of pigmented BCC contain increased brown or black pigment and are most common in individuals with dark skin (see Media File 7).
• Cystic BCC: Lesions of cystic BCC are translucent blue-gray cystic nodules that may mimic benign cystic lesions.
• Superficial BCC: This variety appears as scaly patches or papules that are pink to red-brown, often with central clearing. A threadlike border is common. Erosion is less common in superficial BCC than in nodular BCC (see Media File 1). Superficial BCC is common on the trunk and has little tendency to become invasive. The papules may mimic psoriasis or eczema, but they are slowly progressive and not prone to fluctuate in appearance. Numerous superficial BCCs may indicate arsenic exposure.
• Micronodular BCC: This aggressive BCC subtype has the typical BCC distribution. It is not prone to ulceration, it may appear yellow-white when stretched, and it is firm to the touch. It may have a seemingly well-defined border.
• Morpheaform and infiltrating BCC: These are aggressive BCC subtypes with sclerotic (scarlike) plaques or papules. The border is usually ill defined and often extends well beyond clinical margins. Ulceration, bleeding, and crusting are uncommon. It may be mistaken for scar tissue (see Media 8 and Media File 10).

Causes

• UV radiation: This is the most important and common cause of BCC. Short-wavelength UV radiation (290-320 nm, sunburn rays) is believed to play a greater role in BCC formation than long-wavelength UVA radiation (320-400 nm, tanning rays). In addition, chronic sun exposure appears to be important in the development of BCC. A latency period of 20-50 years is typical between the time of UV damage and the clinical onset of BCC.
• Other radiation: X-ray and grenz-ray exposure are associated with BCC formation.
• Arsenic exposure: Chronic exposure to arsenic is associated with BCC development. Exposure may be medicinal, occupational, or dietary. A contaminated water supply is most commonly implicated.
• Immunosuppression: Immunosuppression is associated with a modest increase in the risk of BCC.
• Xeroderma pigmentosum: This autosomal recessive disease predisposes people to rapid aging of exposed skin, starting with pigmentary changes and progressing to BCC, squamous cell carcinoma, and malignant melanoma. The effects are due to an inability to repair UV-induced DNA damage. Other features include corneal opacities, eventual blindness, and neurologic deficits.
• Nevoid BCC syndrome (basal cell nevus syndrome, Gorlin syndrome): Multiple BCCs occur in this autosomal dominant condition, often starting at an early age. Odontogenic keratocysts, palmoplantar pitting, intracranial calcification, and rib anomalies may be seen. Various tumors, such as medulloblastomas, meningioma, fetal rhabdomyoma, and ameloblastoma, can also occur. Mutations in the hedgehog signaling pathway, particularly the PTCH gene, are causative.⁴
• Bazex syndrome (Bazex-Dupre-Christol syndrome): This is an x-linked dominant condition with features of follicular atrophoderma (ice-pick marks, especially on dorsum of the hands), multiple BCCs, local anhidrosis (decreased or absent sweating), and congenital hypotrichosis.⁵
• Rombo syndrome: This is an autosomal dominant condition distinguished by BCC  and atrophoderma vermiculatum, trichoepitheliomas, hypotrichosis milia, and peripheral vasodilation with cyanosis.
• History of nonmelanoma skin cancer (BCC or squamous cell carcinoma): Persons with one nonmelanoma skin cancer are at increased risk of developing others in the future. The rate of new nonmelanoma skin cancer is 35% at 3 years and 50% at 5 years after an initial diagnosis of skin cancer.⁶

DIFFERENTIALS

Section 4 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

WORKUP

Section 5 of 10  

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• Treatment
• Medication
• Follow-up
• Multimedia
• References

Procedures

• Skin biopsy: Biopsy is required to confirm the diagnosis and to identify the histologic subtype of the BCC. Shave or punch biopsy is usually performed. Additional workup is rarely necessary, unless a genetic disorder is suspected.
• • Shave biopsy suffices for the diagnosis of most BCCs. Avoid taking an exceedingly superficial biopsy specimen because missing the tumor is possible. For example, an ulcerated BCC may reepithelialize with normal epidermis while a tumor is present at a deeper level. Part or all of the BCC may be sampled, but avoid going beyond the clinical margins if the biopsy is only for diagnostic purposes.
  • Punch biopsy is an easy method to obtain a thick specimen. The most suspicious area of a lesion may be sampled, or multiple biopsy samples may be taken if the tumor has different appearances in different areas. Avoid punch biopsy if curettage is planned for final treatment.

Histologic Findings

Tumor cells of nodular BCC, sometimes called basalioma cells, typically have large, hyperchromatic, oval nuclei and little cytoplasm. Cells appear uniform, and, if present, mitotic figures are usually few. Nodular tumor aggregates may be of varying sizes, but tumor cells tend to align more densely in a palisade pattern at the periphery of these nests (see Media File 3). Early lesions usually have some connection to the overlying epidermis, but such contiguity may be difficult to appreciate in more advanced lesions. Increased mucin is often present in the surrounding dermal stroma.

Cleft formation, known as retraction artifact, commonly occurs between BCC nests and stroma because of shrinkage of mucin during tissue fixation and staining. Some lobules may have areas of pseudoglandular change, and this is the predominant change in adenoid BCC. In other instances, large tumor lobules may degenerate centrally, forming pseudocystic spaces filled with mucinous debris. These changes are seen in the nodulocystic variant of BCC (see Media File 6).

Numerous variants occur, including pigmented BCC, in which benign melanocytes in and around the tumor produce large amounts of melanin. These melanocytes contain many melanin granules in their cytoplasm and dendrites. Superficial BCC appears as buds of basaloid cells attached to the undersurface of the epidermis. Nests of various sizes are often seen in the upper dermis. The tumor cell aggregates typically show peripheral palisading.

The more aggressive morpheaform and infiltrating BCCs have growth patterns resulting in strands of cells rather than round nests. Morpheaform BCC arises as thin strands of tumor cells (often only 1 cell in thickness) that are embedded in a dense fibrous stroma. The strands of infiltrating BCC tend to be somewhat thicker than those seen in morpheaform BCC, and they have a spiky, irregular appearance. Infiltrating BCC usually does not exhibit the scarlike stroma seen in morpheaform BCC. Peripheral palisading and retraction are less pronounced in morpheaform and infiltrating BCC than in less aggressive forms of the tumor, and subclinical involvement is often extensive.

Another aggressive variant, micronodular BCC, appears as small, nodular aggregates of basaloid cells. Retraction artifact tends to be less pronounced than in the nodular form of BCC, and subclinical involvement is often significant. Basosquamous carcinoma, which exhibits features of both BCC and squamous cell carcinoma, is also considered an aggressive skin cancer.

TREATMENT

Section 6 of 10  

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Medical Care

Local therapy with chemotherapeutic and immune-modulating agents is useful in some cases of BCC. In particular, small and superficial BCC may respond to these compounds. In addition, they may be used for prophylaxis or maintenance in patients who are prone to having many BCCs, such as those with basal cell nevus syndrome. See Medication.

Surgical Care

The goal of surgical treatment of BCC is to destroy or remove the tumor so that no malignant tissue is allowed to proliferate further. Factors to consider when choosing therapy include the histologic subtype of BCC, the location and size of tumors, the age of the patient, the patient's ability to tolerate surgery, and the expense. Recurrent tumors are generally more aggressive than primary lesions, and subclinical extension also tends to be increased. Tumors that are aggressive and those occurring near vital or cosmetically sensitive structures are best treated with methods that allow for an examination of the tissue margins.

The most common surgical methods are curettage, excision with margin examination, Mohs micrographic surgery, and radiotherapy. Additionally, cryotherapy is sometimes used to treat these tumors (see Media File 9).

• Curettage (usually with electrodesiccation)⁷
• • A looped blade (curette) is used to vigorously scrape tumor away from adjacent normal skin. One may start with a larger curette to debulk the tumor and then follow with a smaller curette to better remove smaller fragments of tumor from surrounding stroma. This technique works best in nodular or superficial BCC because these tumors tend to be friable and do not tend to be embedded in fibrous stroma. The instrument is applied firmly and used in multiple directions over the tumor and immediately adjacent skin. Curetting is most often followed by electrodesiccation, and the entire process may be repeated 1-2 more times. If electrodesiccation is not performed, vigorous and firm scraping in several directions is especially important. Many recurrences after curettage are believed to be due to insufficient aggressiveness on the part of the surgeon. The overall cure rate exceeds 90% for low-risk BCCs. The method is quick, simple, and less expensive than most other methods.
  • Curettage is a blind technique in which the specimen cannot be examined for margin control. This lack of microscopic margin control limits the usefulness of curettage in high-risk areas, such as the face and ears. Furthermore, the aggressive subtypes of BCC, such as morpheaform, infiltrating, micronodular, and recurrent tumors, are usually not friable and therefore unlikely to be removed by using the curette. The success of this treatment, even in nonaggressive tumors in low-risk sites, highly depends on the operator's experience and technique. Finally, healing by secondary intention (granulation) often leads to atrophic, white scars that may not be satisfactory in aesthetically important areas.
• Surgical excision⁸
• • One may surgically excise the clinically apparent tumor and a margin of clinically normal–appearing skin. This method can usually be performed in an ambulatory setting and provides the pathologist with a specimen to examine the tissue margins. Healing time is generally shorter with sutured closure than with granulation, and cosmesis compares favorably with that of curettage.
  • Surgical excision is more time-consuming and costly than curettage. In addition, this method requires sacrifice of normal tissue to obtain acceptable cure rates. Margins of at least 4 mm are needed, even with the least aggressive BCCs, to achieve 95% cure rates. If standard bread-loaf tissue sectioning is used, areas of margin involvement may be missed under microscopy because only a small sampling of the specimen is evaluated.
• Mohs micrographic surgery^{9, 10}
• • Mohs surgery involves removal of the clinically apparent tumor and a thin rim of normal-appearing skin around the defect. This saucer-shaped tissue specimen represents tissue adjacent to the tumor or the margin surrounding the tumor. This margin specimen is sectioned and marked so that the entirety of the undersurface and outer edges of the tumor are examined microscopically to minimize sampling error. Use of the frozen-section technique allows for an examination of tissue while the patient is in the office. Tissue is mapped microscopically so if any foci of tumor persist, further excision can be directed to only those areas to spare the normal tissue.
  • With the Mohs technique, almost 100% of the tissue margins are examined, compared with standard vertical (bread-loaf) sectioning, in which less than 1% of the outer margins are examined. Because relatively thin layers are taken only in areas of proven tumor, this technique is tissue sparing. Excision and repair can usually be performed on the same day. Of most importance, Mohs micrographic surgical excision has the best long-term cure rates of any treatment modality for BCC. Cure rates for primary BCC are 98-99% with Mohs excision and 94-96% for recurrent BCC.
  • Chief disadvantages of Mohs surgery are its increased expense and time requirement compared with curettage. Mohs excision compares favorably with standard surgical excision when one factors in the savings of treating fewer recurrences with this technique.
• Radiation therapy¹¹
• • Radiation therapy is effective as primary treatment for a variety of BCCs. For most BCCs, cure rates approach 90%. It is especially useful for patients who cannot easily tolerate surgery, such as elderly or debilitated individuals. Irradiation can also be a useful adjunct when patients have aggressive tumors that were treated surgically or when surgery has failed to clear the margins of the tumor. Radiation is also an excellent option in patients who refuse surgery because of the size of a lesion or its proximity to vital structures.
  • Initial cosmetic results tend to be good, and this therapy can be less disfiguring than surgical excision. However, long-term results after several years can be deforming. Another disadvantage of this technique is that surgical margins cannot be examined. Tumors recurring in previously radiated sites tend to be aggressive and difficult to treat and reconstruct. Radiation therapy remains an important, feasible option in selected patients with BCC.
• Cryotherapy
• • Cryotherapy is also an effective treatment for most nonaggressive BCCs, with cure rates near 90%. However, successful treatment is highly dependent on the experience of the operator. Optimal cure rates are obtained when the depth, duration, and temperature of treatment are measured with special instrumentation, such as cryoprobes.
  • Patients must be willing to endure the immediate posttreatment swelling, resultant necrosis of treated areas, and unpredictable scarring that can occur with this approach.
  • This method is not commonly used for the treatment of BCC, except by a few experienced cryosurgeons.

MEDICATION

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Imiquimod 5% cream¹² has been used successfully to treat superficial BCCs.^{13, 14} Although its exact mode of action in treating BCC is not known, a few suggested mechanisms follow. Lymphocytes, dendritic cells, and macrophages may be recruited into the area of imiquimod application. These cells may be activated via toll-like receptors 7 and 8 (both of which recognize imiquimod as a ligand) to release cytokines, particularly tumor necrosis factor-alpha, interferon-alpha, and interleukin 6. Antitumor effects, such as apoptosis, may then proceed, thereby inducing tumor regression.¹⁵ Induction of tumor suppressor function via the Notch signaling pathway in superficial BCCs has also been suggested as a mechanism of imiquimod.^{14, 16} 
 
The current recommended dosing frequency for the treatment of superficial BCC is 5 times per week for 6 weeks, but the frequency and duration should be tailored to the individual patient's response and ability to tolerate the medication. Many application schedules have been used, ranging from 3 times per week to twice daily 7 d/wk. The duration of treatment varies from 6-16 weeks. Superficial BCC cure rates of 70-100% should be expected after a 6-week course of 5-times-per-week application, as shown in studies. Topical imiquimod has also been used to treat small, nodular BCCs in low-risk locations, but cure rates have been lower than those with superficial BCCs. Although successful use of imiquimod in immunosuppressed populations (eg, transplantation patients) without systemic complications has been documented, it has not been widely studied, nor have safety and efficacy been established. Imiquimod should be used cautiously in patients with autoimmune disease. Additionally, its high cost may prohibit its use in some patients.
 
Topical 5-fluorouracil 5% cream¹⁷ is sometimes used to treat small, superficial BCCs. It is a fluorinated pyrimidine that "blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell."
 
In properly selected (eg, thin) tumors, cure rates of approximately 80% have been obtained. It is generally applied twice daily and must be used for at least 6 weeks for the treatment of superficial BCC. Percutaneous absorption of 5-fluorouracil is its major limiting factor; it penetrates only 1 mm into the skin. New vehicles that may enhance absorption of 5-fluorouracil are being investigated.

One advantage of 5-fluorouracil use is that it can act on BCCs that are not large enough to be seen with the unaided eye. Therefore, it may be used in patients with basal cell nevus syndrome or in individuals prone to develop many BCCs to preemptively treat subclinical tumors. Patients with BCCs that are treated with 5-fluorouracil should be monitored carefully because not all tumors completely respond. Cosmetic results tend to range from good to excellent with the use of 5-fluorouracil. Although it is not inexpensive, it does cost less than imiquimod.

Interferon alfa-2b has shown some success in treating small (<1 cm), nodular, and superficial BCCs. It is administered intralesionally, 3 times per week for 3 weeks. The recommended dose is 1.5 million units per injection (total of 13.5 million U). In appropriate BCC tumors, cures rates of up to 80% have been obtained. Interferon has not become a mainstay in BCC treatment because of its cost, the inconvenience of multiple visits, the discomfort of administration, and its adverse effects. Flulike symptoms, which are dose related, are common with the doses administered to treat BCCs. Cardiovascular, myelodepressive, and neurologic adverse effects are less common with this treatment than with others. Because interferon is an immune stimulant, it should not be used to treat BCC in transplant recipients or in individuals with autoimmune diseases.

Photodynamic therapy (PDT) for BCCs has been used for more than 20 years.¹⁸ PDT is the process of using specific wavelengths of light to photoexcite porphyrins that have been applied to neoplastic and preneoplastic cells. This increased energy is rapidly absorbed by adjacent tissue oxygen, causing the formation of singlet oxygen radicals. These radicals rapidly react with adjacent tissue and destroy it. 5-Aminolevulinic acid is the only US Food and Drug Administration approved photoreactive molecule for PDT in the United States, and it is only approved for actinic keratoses. It is photoactivated with blue light for 1000 seconds after 1 hour of incubation.

Drug Category: Antineoplastic agents

Topical or intralesional antineoplastic agents may be administered depending on the type, location, and stage of the BCC.

FOLLOW-UP

Section 8 of 10  

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• Differentials
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• Follow-up
• Multimedia
• References

Prognosis

• BCCs treated incompletely can recur.
• All treated sites must be monitored after therapy.
• Individuals with BCC have a 30% greater risk of having another BCC unrelated to the previous lesion compared with the risk in the general population.

Patient Education

• Avoidance of exposure to UV radiation is encouraged. Helpful preventive measures include carefully planning outdoor activities before 10 am and after 4 pm, wearing a broad-brimmed hat during outdoor activities, and using sunscreens with sun protection factor of 30 or higher.

• For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Burns Center. In addition, see eMedicine's patient education articles Skin Cancer, Skin Biopsy, and Sunburn.

MULTIMEDIA

Section 9 of 10  

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Media file 1:  This translucent pink papule has telangiectases and a crusted erosion, characteristic of nodular basal cell carcinoma.
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Media file 2:  Nodular basal cell carcinoma appearing as a waxy, translucent papule with central depression and a few small erosions.
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Media file 3:  Nodular basal cell carcinoma. Nodular aggregates of basalioma cells are present in the dermis and exhibit peripheral palisading and retraction artifact. Melanin is also present within the tumor and in the surrounding stroma, as seen in pigmented basal cell carcinoma.
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Media file 4:  Scale, erythema, and a threadlike raised border are present in this superficial basal cell carcinoma on the trunk.
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Media file 5:  Large, superficial basal cell carcinoma.
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Media file 6:  Histology of superficial basal cell carcinoma. Nests of basaloid cells are seen budding from the undersurface of the epidermis.
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Media file 7:  Pigmented basal cell carcinoma has features of nodular basal cell carcinoma with the addition of dark pigmentation from melanin deposition. The pigmentation often has the appearance of dark droplets in the lesion, as shown here.
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Media file 8:  This infiltrating basal cell cancer has ill-defined borders and telangiectases.
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Media file 9:  Postoperative wound after Mohs micrographic surgery demonstrates extensive subclinical involvement typical of many infiltrating and morpheaform basal cell carcinomas.
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Media file 10:  Large, scarlike morpheaform basal cell cancer.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
• Multimedia
• References

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14. Sapijaszko MJ. Imiquimod 5% cream (Aldara) in the treatment of basal cell carcinoma. Skin Therapy Lett. Jul-Aug 2005;10(6):2-5. [Medline]. [Full Text].
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16. Wuest M, Dummer R, Urosevic M. Induction of the members of Notch pathway in superficial basal cell carcinomas treated with imiquimod. Arch Dermatol Res. Dec 2007;299(10):493-8. [Medline].
17. Efudex (fluorouracil) [package insert]. Valeant Pharmaceuticals; 2005.
18. Braathen LR, Szeimies RM, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, et al. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. Jan 2007;56(1):125-43. [Medline].
19. Rhodes LE, de Rie MA, Leifsdottir R, Yu RC, Bachmann I, Goulden V, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol. Sep 2007;143(9):1131-6. [Medline].
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21. Frankel DH, Hanusa BH, Zitelli JA. New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin. Implications and recommendations for follow-up. J Am Acad Dermatol. May 1992;26(5 Pt 1):720-6. [Medline].
22. Fritsch P. Dermatologie und Venerologie. 2^nd ed. Berlin, Germany: Springer; 2004.
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Article Last Updated: Jan 8, 2008