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Basal cell carcinoma

 
Basal Cell Carcinoma

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Basal cell carcinoma



 
 
Basal cell carcinoma is the most common of all types of skin cancer
Skin cancer

Skin cancer is a malignant growth on the skin which can have many causes. The most common skin cancers are basal cell cancer, squamous cell cancer, and melanoma....
. Statistically speaking, approximately 3 out of 10 caucasians develop a basal cell cancer within their lifetime. Although it is considered a malignancy, it rarely metastasizes or kills. Metastasis is rare, but when neglected, it can invade locally. In 80 percent of all cases, basal cell cancers are found on the head and neck. There appear to be an increase in incidence of basal cell cancer in the trunk in recent years.






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Basal cell carcinoma is the most common of all types of skin cancer
Skin cancer

Skin cancer is a malignant growth on the skin which can have many causes. The most common skin cancers are basal cell cancer, squamous cell cancer, and melanoma....
. Statistically speaking, approximately 3 out of 10 caucasians develop a basal cell cancer within their lifetime. Although it is considered a malignancy, it rarely metastasizes or kills. Metastasis is rare, but when neglected, it can invade locally. In 80 percent of all cases, basal cell cancers are found on the head and neck. There appear to be an increase in incidence of basal cell cancer in the trunk in recent years. Even though it is not deadly, it can be locally destructive and disfiguring.

Variants of basal cell cancers

Various forms are recognized:
  • Nodular: flesh-colored to pearly or translucent papule with telangiectasis; if it ulcer
    Ulcer

    An ulcer is a discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat....
    ates, it becomes a "rodent ulcer" (ulcus rodens), an ulcerating nodule with (often) a pearly border.
  • Cystic: rarer and difficult to distinguish from the nodular form, which has a central cavity with fluid
  • Pigmented: a variant of the nodular form that may be confused with melanoma
    Melanoma

    Melanoma is a malignant tumor of melanocytes which are found predominantly in skin but also in the bowel and the eye . It is one of the rarer types of skin cancer but causes the majority of skin cancer related deaths....
  • Sclerosing/cicatrizing or Morpheaform: a scar-like lesion. Also called "infiltrative".
  • Superficial: a red scaly localized patch. It is frequently confused with psoriasis or eczema.
  • Basal cell cancer with squamous differentiation: Or Baso-squamoid variant. Often consider to be more aggressive, and should be treated with respect especially when found on the ears, lips, or in immunosuppressed individuals. Probably is responsible for the reported deaths and metastasis. It behaves more like a squamous cell carcinoma
    Squamous cell carcinoma

    In medicine, squamous cell carcinoma is a form of cancer of the carcinoma type that may occur in many different organs, including the skin, lips, mouth, esophagus, urinary bladder, prostate, lungs, vagina, and cervix....
     than a basal cell cancer.
  • Fibroepithelioma of Pinkus an unusual and uncommon form of basal cell cancer with the appearance of a skin tag or pedunculated intradermal nevus.


Distribution


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 the basal cell cancer patients.

Diagnosis

To diagnose basal cell carcinomas, a skin biopsy
Skin biopsy

Skin biopsy is a biopsy technique in which a skin lesion is removed and sent to the pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 days....
 (where tissue is taken for pathological study) is done using local anesthesia. The most common method is with a shave biopsy. It is done under local anesthetic. 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.

Pathophysiology

Basal Cell Carcinoma Pathology
Basal cell carcinomas develop in the basal cell layer of the skin
Skin

The skin is the outer covering of the body, also known as the epidermis. It is the largest organ of the integumentary system made up of multiple layers of epithelial biological tissue, and guards the underlying muscles, bones, ligaments and organ s....
. Sun light exposure leads to the formation of thymine dimer
Thymine dimer

A thymine dimer is the covalent bonding of two adjacent thymine residues within a DNA molecule, often catalyzed by ultraviolet radiation or chemical mutagenic agents....
s, a form of DNA damage. While DNA repair
DNA repair

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolism activities and environmental factors such as UV light and Radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell pe...
 removes most UV-induced damage, not all crosslinks are excised. There is, therefore, cumulative DNA damage leading to mutation
Mutation

In biology, mutations are changes to the nucleotide sequence of the genetic material of an organism. Mutations can be caused by copying errors in the genetic material during cell division, by exposure to ultraviolet or ionizing radiation, chemical mutagens, or virus , or can be induced by the organism, itself, by cellular processes such as s...
s. Apart from the mutagenesis, sunlight depresses the local immune system
Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
, possibly decreasing immune surveillance for new tumor cells.

Basal-cell carcinoma also develops as a result of basal-cell nevus syndrome, or Gorlin's syndrome, which is also characterized by odontogenic keratocysts of the jaw, palmar or plantar (sole of the foot) pits, calcification of the falx cerebri
Falx cerebri

The falx cerebri, also known as the cerebral falx, so named from its sickle-like form, is a strong, arched fold of dura mater which descends vertically in the longitudinal fissure between the cerebral hemispheres....
 (in the center line of the brain) and rib abnormalities. The cause of the syndrome is a mutation in the PTCH1
PTCH1

Patched homolog 1 , also known as PTCH1, is a human gene.ReferencesFurther reading...
 tumor-suppressor gene at chromosome 9q22.3, which inhibits the hedgehog signaling pathway
Hedgehog signaling pathway

In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts....
. A mutation in the SMO
Smoothened

Smoothened is a G protein-coupled receptor protein encoded by the gene of the hedgehog conserved from Drosophila to humans. It is the molecular target of the teratogen cyclopamine....
 gene, which is also on the hedgehog pathway, also causes basal-cell carcinoma.

Prevention and early diagnosis

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, but one-third occur in non-sun-exposed areas. Therefore, doctors recommend sun screens.

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.

Treatment

The following methods are employed in the treatment of basal cell carcinoma (BCC):
  • Standard surgical excision with either frozen section histology, or parafin 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 dermatoscopy
    Dermatoscopy

    Dermatoscopy is the examination of skin lesions with a dermatoscope, a magnifier with a light and a liquid medium between the instrument and the skin, thus illuminating the lesion without reflected light....
     can help an experienced surgeon accurately identify the visible tumour that the naked eye can not see. The narrower the free 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. On the face, or on recurrent basal cell cancer after previous surgery, special margin controlled processing (ccpdma - complete circumferential peripheral and deep margin assessment) using frozen section histology (Mohs surgery
    Mohs surgery

    Mohs surgery, also known as chemosurgery, was created by a general surgeon, Dr. Fredrick E. Mohs, is microscopically controlled surgery that is highly effective for common types of skin cancer, with a cure rate cited by most studies between 97% and 99.8% for primary basal cell carcinoma, the most common type of skin cancer....
     is one of the methods) is required. With 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 microns 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 margin is obtained around a small tumor (less than 6mm), or a wider 6 mm free 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
    Mohs surgery

    Mohs surgery, also known as chemosurgery, was created by a general surgeon, Dr. Fredrick E. Mohs, is microscopically controlled surgery that is highly effective for common types of skin cancer, with a cure rate cited by most studies between 97% and 99.8% for primary basal cell carcinoma, the most common type of skin cancer....
     or frozen section histology with either margin control 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 patient 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
    Mohs surgery

    Mohs surgery, also known as chemosurgery, was created by a general surgeon, Dr. Fredrick E. Mohs, is microscopically controlled surgery that is highly effective for common types of skin cancer, with a cure rate cited by most studies between 97% and 99.8% for primary basal cell carcinoma, the most common type of skin cancer....
     (or Mohs micrographic surgery) is an outpatient procedure in which the tumor is surgically excised and then immediately examined under a microscope. It is claimed to have the highest cure rate of 97% to 99.8% by some individuals. 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
    Squamous cell carcinoma

    In medicine, squamous cell carcinoma is a form of cancer of the carcinoma type that may occur in many different organs, including the skin, lips, mouth, esophagus, urinary bladder, prostate, lungs, vagina, and cervix....
    ; 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
    Chemotherapy

    Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
     agent. Topical treatment with 5% Imiquimod
    Imiquimod

    Imiquimod is a prescription medication that acts as an immune response modifier. It is marketed by MEDA AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade name Aldara and by Mochida as Beselna....
     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 has 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
    Mohs surgery

    Mohs surgery, also known as chemosurgery, was created by a general surgeon, Dr. Fredrick E. Mohs, is microscopically controlled surgery that is highly effective for common types of skin cancer, with a cure rate cited by most studies between 97% and 99.8% for primary basal cell carcinoma, the most common type of skin cancer....
     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 individual 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
    Immunotherapy

    Immunotherapy, in medicine, refers to an array of treatment strategies based upon the concept of modulating the immune system to achieve a Prophylaxis and/or Immunosuppressive therapy goal....
     research suggests that treatment using Euphorbia peplus
    Euphorbia peplus

    Euphorbia peplus is a species of Euphorbia, native to most of Europe, northern Africa, and western Asia, where it typically grows in cultivated arable land, gardens, and other disturbed land....
    , a common garden weed, may be effective. Australian biopharmaceutical company Peplin is developing this as topical treatment for BCC. Imiquimod
    Imiquimod

    Imiquimod is a prescription medication that acts as an immune response modifier. It is marketed by MEDA AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade name Aldara and by Mochida as Beselna....
     or Aldara is an immunotherapy but is listed here under chemotherapy.


  • Radiation: Radiation therapy
    Radiation therapy

    Radiation therapy is the medicine use of ionizing radiation as part of cancer oncology to control malignant cell s . Radiotherapy may be used for curative or Adjuvant chemotherapy cancer treatment....
     is appropriate for all forms of BCC as adequate doses will eradicate the disease. 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 visit 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. 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
    Photodynamic therapy

    Photodynamic therapy , matured as a feasible medical technology in the 1980s at several institutions throughout the world, is a third-level treatment for cancer involving three key components: a photosensitizer, light, and tissue oxygen....
     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
    Methyl aminolevulinate

    Methyl aminolevulinate is a prodrug that is metabolised to Protoporphyrin IX used in photodynamic therapy....
     is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types.


  • Cryosurgery: Cryosurgery
    Cryosurgery

    Cryosurgery is the application of extreme cold to destroy abnormal or diseased tissue. The term comes from the Greek words cryo and surgery meaning "hand work" or "handiwork"....
     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. Several textbooks are published on the therapy, and a few physicians still apply the treatment to selected patients.


  • Electrodessication 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. 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 criteria can not be supported. The cure rate can be low or high, depending on the aggressiveness of the EDC and the free margin treated. Some advocates curettage alone without electrodessication, 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

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
Metastasis

Metastasis , or Metastatic disease, sometimes abbreviated mets, is the spread of a disease from one Organ or part to another non-adjacent organ or part....
, it grows locally with invasion and destruction of local tissues. The cancer can impinge on vital structures and result in loss of extension or loss of function or rarely death
Death

Death is the permanent termination of the biological functions that define a life organism. It refers to both a particular event and to the condition that results thereby....
. The vast majority of cases can be successfully treated before serious complications occur. The recurrence rate for the above treatment options ranges from 50% to 1% or less.

Epidemiology

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 , there are approximately 800,000 new cases yearly in the United States
United States

The United States of America is a Federal government constitutional republic comprising U.S. state and a federal district. The country is situated mostly in central North America, where its Contiguous United States and Washington, D.C., the Capital districts and territories, lie between the Pacific Ocean and Atlantic Oceans, Borders of the U...
 alone. Up to 30% of caucasians develop basal cell carcinomas in their life time.

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
Nevoid basal cell carcinoma syndrome

The Nevoid Basal Cell Carcinoma Syndrome is an inherited group of multiple defects involving the skin, nervous system, eyes, endocrine system, and bones....
.

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