eMedicine Specialties > Dermatology > Malignant Neoplasms

Basal Cell Carcinoma

Author: Michael L Ramsey, MD, Director, Mohs Surgery Fellowship, Co-Director, Procedural Dermatology Fellowship, Department of Dermatology, Geisinger Medical Center
Coauthor(s): Lindsay Dane Sewell, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Contributor Information and Disclosures

Updated: Jul 15, 2010

Introduction

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 basal cell carcinomas (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

Basal cell carcinoma (BCC) is the most common cancer, with more than 1 million cases each year in the United States, and it represents about 80% of all skin cancer cases.4 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

Basal cell carcinoma (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

Basal cell carcinoma (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 for basal cell carcinoma (BCC) is approximately 3:2.

Age

Basal cell carcinoma (BCC) most commonly occurs in adulthood, especially in elderly persons.

Clinical

History

Basal cell carcinoma (BCC) patients often present with a slowly growing, 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 basal cell carcinoma (BCC) may exhibit different patterns of behavior. Recognizing the various types is important because more aggressive therapy is often necessary for higher risk 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. These lesions often blanch when the skin is stretched or squeezed, making their clinical margins more apparent. 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 images below)
    • Pearly appearance
    • Erosion or ulceration
    • Bleeding
    • Crusting
    • Rolled (raised) border (see images below)
    • Translucency
    • Telangiectases over the surface
    • History of bleeding with minor trauma

    • Nodular basal cell carcinoma appearing as a waxy,...

      Nodular basal cell carcinoma appearing as a waxy, translucent papule with central depression and a few small erosions.

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      Nodular basal cell carcinoma appearing as a waxy,...

      Nodular basal cell carcinoma appearing as a waxy, translucent papule with central depression and a few small erosions.


    • Scale, erythema, and a threadlike raised border a...

      Scale, erythema, and a threadlike raised border are present in this superficial basal cell carcinoma on the trunk.

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      Scale, erythema, and a threadlike raised border a...

      Scale, erythema, and a threadlike raised border are present in this superficial basal cell carcinoma on the trunk.


    • Large, superficial basal cell carcinoma.

      Large, superficial basal cell carcinoma.

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      Large, superficial basal cell carcinoma.

      Large, superficial basal cell carcinoma.

  • 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 image below).

  • Pigmented basal cell carcinoma has features of no...

    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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    Pigmented basal cell carcinoma has features of no...

    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.

  • Cystic BCC: Lesions of cystic BCC are translucent blue-gray pseudocystic 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 image below). 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.

  • This translucent pink papule has telangiectases a...

    This translucent pink papule has telangiectases and a crusted erosion, characteristic of nodular basal cell carcinoma.

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    This translucent pink papule has telangiectases a...

    This translucent pink papule has telangiectases and a crusted erosion, characteristic of nodular basal cell carcinoma.

  • 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 images below).

  • This infiltrating basal cell cancer has ill-defin...

    This infiltrating basal cell cancer has ill-defined borders and telangiectases.

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    This infiltrating basal cell cancer has ill-defin...

    This infiltrating basal cell cancer has ill-defined borders and telangiectases.


  • Large, scarlike morpheaform basal cell cancer.

    Large, scarlike morpheaform basal cell cancer.

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    Large, scarlike morpheaform basal cell cancer.

    Large, scarlike morpheaform basal cell cancer.

Younger patients (<40 y) may have a lower prevalence of BCC on the head and neck and a higher prevalence on the trunk, with greater tendency to superficial BCC, than in older patients.5 Childhood BCC is exceedingly rare in the absence of other underlying conditions. Only 107 cases of de novo childhood BCC have been reported in the literature, but the majority (90%) occurred on the head and neck, and aggressive subtypes were observed in 20% of the total cases.6

Causes

  • UV radiation: This is the most important and common cause of basal cell carcinoma (BCC). Both short-wavelength UV radiation (290-320 nm, sunburn rays) and longer wavelength UVA radiation (320-400 nm, tanning rays) contribute to the formation of BCC. In particular, 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 but a much greater increase in squamous cell carcinoma.
  • 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.7
  • 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.8
  • Rombo syndrome9 : 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.10

More on Basal Cell Carcinoma

Overview: Basal Cell Carcinoma
Differential Diagnoses & Workup: Basal Cell Carcinoma
Treatment & Medication: Basal Cell Carcinoma
Follow-up: Basal Cell Carcinoma
Multimedia: Basal Cell Carcinoma
References
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Further Reading

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Contributor Information and Disclosures

Author

Michael L Ramsey, MD, Director, Mohs Surgery Fellowship, Co-Director, Procedural Dermatology Fellowship, Department of Dermatology, Geisinger Medical Center
Michael L Ramsey, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, and Pennsylvania Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Lindsay Dane Sewell, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Lindsay Dane Sewell, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

R Stan Taylor, MD, Professor of Dermatology, University of Texas Southwestern Medical School; Director of Skin Surgery and Oncology Clinic, Department of Dermatology, University of Texas Southwestern Medical Center
R Stan Taylor, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, Christian Medical & Dental Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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