Basal cell carcinoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2] Saarah T. Alkhairy, M.D.,

Basal cell carcinoma is one of the most common skin cancers. It is commonly known as rodent ulcer. In 1827, Jacob Arthur, reported the “rodent ulcer“. In 1900, Edmund Krompecher, identified the histological features as an epithelial carcinoma. The annual incidence of basal cell carcinoma in the United States is approximately 2.8 million which increases with increasing age. Men and white skinned people are affected relatively more, especially in states closer to the equator.There is no well established classification for basal cell carcinoma, however there are few clinical variants which are nodular, cystic, sclerodermiform, infiltrated, micronodular, superficial, and pigment basal cell carcinoma and fibroepithelioma of Pinkus.Although the exact causes were unknown, the following are some of the factors that have been associated with the development of basal cell carcinoma: radiation exposure, gene mutations, xeroderma pigmentosa, epidermodysplastic verruciformis, nevoid basal cell carcinoma syndrome, bazex syndrome, rombo syndrome etc. Environmental and genetic risk factors that may predispose to basal cell carcinoma include radiation exposure, physical characteristics, gender, albinism, xeroderma pigmentosum, epidermodysplastic verruciformis, nevoid basal cell carcinoma syndrome, bazex syndrome, rombo syndrome etc. Its morphology is characterized by pearly pink nodules with telangiectasias, rolled borders, and central crusting with or without an ulcerating lesion. The most common cause for the development of the basal cell carcinoma involves radiation exposure and mutations that involve many genes including sonic hedgehog gene, PTCH1 gene, and other gain-of-function mutations which further depend on the subtypes such as nodular, superficial, Infundibulocystic, fibroepithelial, morpheaform, infiltrative, micronodular, and basosquamous basal cell carcinomas. The U.S. Preventive Services Task Force has found no evidence to recommend for or against screening. It is a slow-growing locally invasive lesion with an unlikely risk of metastasis. Most patients are often asymptomatic. The major complication is its recurrence and involvement of surrounding structures. With appropriate treatment, the prognosis is usually excellent. The history and symptoms of basal cell carcinoma include skin growths on sun-exposed skin, mainly in the form of patches that are shiny, pearly bumps, raised edges with central ulceration. They are fragile and may bleed easily. Skin examination usually show papules, plaques, central ulceration with rolled borders, telangiectasias. Skin biopsy is the diagnostic study of choice for basal cell carcinoma. After the suspicious lesion is evaluated, the medical therapy is divided based on low-risk and high-risk basal cell carcinoma patients. Medical therapy consists of topical and systemic therapy. Among topical therapy imiquimod, photodynamic therapy, 5-fluorouracil are included. Systemic therapy consists of sonic hedgehog pathway inhibitors like vismodegib, sonidegib. Types of surgery for basal cell carcinoma involve electrodesiccation and curettage, surgical excision, mohs micrographic surgery, and cryosurgery. The primary prevention of basal cell carcinoma involves avoidance and protection from the sun like using sunscreen lotions, protective clothing, avoid tanning beds etc. A skin biopsy and chemotherapeutic agents such as 5-Fluorouracil or Imiquimod may prevent the further development of basal cell carcinoma.

In 1827, Jacob Arthur, reported the “rodent ulcer“. In 1900, Edmund Krompecher, identified the histological features as an epithelial carcinoma.

There is no well established classification for basal cell carcinoma, however there are few clinical variants which are nodular, cystic, sclerodermiform, infiltrated, micronodular, superficial, and pigment basal cell carcinoma and fibroepithelioma of Pinkus.

Basal cell carcinoma is one of the most common skin cancers. It is commonly known as rodent ulcer due to its distinct morphology characterized by pearly pink nodules with telangiectasias, rolled borders, and central crusting with or without an ulcerating lesion. The most common cause for the development of the basal cell carcinoma involves radiation exposure and mutations that involve many genes including sonic hedgehog gene, PTCH1 gene, and other gain-of-function mutations which further depend on the subtypes such as nodular, superficial, Infundibulocystic, fibroepithelial, morpheaform, infiltrative, micronodular, and basosquamous basal cell carcinomas.

Although the exact causes were unknown, the following are some of the factors that have been associated with the development of basal cell carcinoma: radiation exposure, gene mutations, xeroderma pigmentosa, epidermodysplastic verruciformis, nevoid basal cell carcinoma syndrome, bazex syndrome, rombo syndrome etc.

There are several differential diagnosis for basal cell carcinoma that may be differentiated clinically or histopathologically including microcystic adnexal carcinoma, trichoepithelioma/trichoblastoma, merkel cell carcinoma, and other squamous cell carcinoma.

The annual incidence of basal cell carcinoma in the United States is approximately 2.8 million which increases with increasing age. Men and white skinned people are affected relatively more, especially in states closer to the equator.

Environmental and genetic risk factors that may predispose to basal cell carcinoma include radiation exposure, physical characteristics, gender, albinism, xeroderma pigmentosum, epidermodysplastic verruciformis, nevoid basal cell carcinoma syndrome, bazex syndrome, rombo syndrome etc.

The U.S. Preventive Services Task Force has found no evidence to recommend for or against screening. The American Cancer Society recommends that a health care provider examine the skin every year if the patient is older than 40 years, and every 3 years if the patient is between 20-40 years.

It is a slow-growing locally invasive lesion with an unlikely risk of metastasis. Most patients are often asymptomatic. The major complication is its recurrence and involvement of surrounding structures. With appropriate treatment, the prognosis is usually excellent.

Skin biopsy is the diagnostic study of choice for basal cell carcinoma.

The American Joint Committee on Cancer (AJCC) stages basal cell carcinoma based on the TNM system. T, M, and N are combined into stages, called stage grouping.

The history and symptoms of basal cell carcinoma include skin growths on sun-exposed skin, mainly in the form of patches that are shiny, pearly bumps, raised edges with central ulceration. They are fragile and may bleed easily.

Patients with basal cell carcinoma usually have normal general appearance. Skin examination usually show papules, plaques, central ulceration with rolled borders, telangiectasias.

There are no laboratory tests available to diagnose basal cell carcinoma.

CT scan is mainly used for the staging of the basal cell carcinoma rather than diagnosing the tumor. CT scan images usually shows hypoattenuating or isoattenuating lesions when compared to adjacent musculature

MRI is useful when the tumor has any adjacent bony or perineural invasion. On T1– it appears as an enhancing isointense lesion. On T2– it appears as an hyperintense lesion.

There are various other techniques for diagnosing basal cell carcinoma, which include Reflectance Confocal Microscopy, Dermatoscopy

After the suspicious lesion is evaluated, the medical therapy is divided based on low-risk and high-risk basal cell carcinoma patients. Medical therapy consists of topical and systemic therapy. Among topical therapy imiquimod, photodynamic therapy, 5-fluorouracil are included. Systemic therapy consists of sonic hedgehog pathway inhibitors like vismodegib, sonidegib.

Types of surgery for basal cell carcinoma involve electrodesiccation and curettage, surgical excision, mohs micrographic surgery, and cryosurgery.

The primary prevention of basal cell carcinoma involves avoidance and protection from the sun like using sunscreen lotions, protective clothing, avoid tanning beds etc

A skin biopsy and chemotherapeutic agents such as 5-Fluorouracil or Imiquimod may prevent the further development of basal cell carcinoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D., Maneesha Nandimandalam, M.B.B.S.[2]

In 1827, Jacob Arthur, reported the “rodent ulcer“. In 1900, Edmund Krompecher, identified the histological features as an epithelial carcinoma.

• In 1827, Jacob Arthur, an Irish ophthalmologist, reported a cutaneous difficult-to-eradicate lesion. He coined the term “rodent ulcer“. Rodent ulcers are now known as an ulcerating basal cell carcinoma.^[1]
• In 1900, Edmund Krompecher, a German physician, identified the features of the rodent ulcer as an epithelial carcinoma.^[1]
• The number of cases of basal cell carcinoma doubled between 1970 and 1986.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D., Maneesha Nandimandalam, M.B.B.S.[2]

There is no well established classification for basal cell carcinoma, however there are few clinical variants which are nodular, cystic, sclerodermiform, infiltrated, micronodular, superficial, and pigment basal cell carcinoma and fibroepithelioma of Pinkus.

• There is no well established classification for the basal cell carcinoma of the skin^[1][2]
• However based on some evidence there are few clinical variants of basal cell carcinoma, the following table summarizes the classification of the clinical variants of basal cell carcinoma (BCC):

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2]

Basal cell carcinoma is one of the most common skin cancers. It is commonly known as rodent ulcer due to its distinct morphology characterized by pearly pink nodules with telangiectasias, rolled borders, and central crusting with or without an ulcerating lesion. The majority common cause for the development of the basal cell carcinoma involves radiation exposure and mutations that involve many genes including sonic hedgehog gene, PTCH1 gene, and other gain-of-function mutations which further depend on the subtypes such as nodular, superficial, Infundibulocystic, fibroepithelial, morpheaform, infiltrative, micronodular, and basosquamous basal cell carcinomas.

The exact pathogenesis of basal cell carcinoma is not completely understood

The development of basal cell carcinoma is the result of multiple genetic mutations such as sonic hedgehog pathway mutations, and PTCH1 gene mutations

• A number of aberrations involving the sonic hedgehog signaling pathway(SHH) are noted.^[1][2][3][4]
• This pathway is vital for the regulation of cell growth, and differentiation and loss of inhibition of this pathway is associated with development of basal cell cancer.
• The majority of mutations in sporadic basal cell carcinoma and basal cell nevus syndrome(BCNS) patients occur in PTCH1 gene, a protein that inhibits smoothened gene (SMO).
• The second most common mutation in sporadic basal cell carcinoma and basal cell nevus syndrome(BCNS) patients are gain-of-function mutations of the smoothened gene (SMO).
• Loss of PTCH1 results in the failure of Smoothened inhibition, subsequently leading to increases in GLI1 levels, changes in transcription, and subsequent tumorigenesis.
• Gain-of-function smoothened(SMO) mutations also leads to increased GLI1 levels and tumorigenesis

Other Genetic Changes:

• Point mutations in the TP53 gene, the tumor supressor gene are the second most common genetic alteration noticed in BCCs
• Some mutations in the CDKN2A locus and in ras gene family (H-ras, K-ras, and N-ras) are also identified in a smaller proportion of sporadic BCCs

• Basal cell carcinomas develop in the basal cell layer of the skin.^[5]
• Cumulative DNA damage caused by chronic sunlight exposure results in DNA mutations that predispose to the development of basal cell carcinoma.
• While DNA repair eliminates most UV-induced damage, not all cross-links are excised, which eventually results in mutations.
• Apart from the mutagenesis, sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells.

• On gross and microscopic histopathological analysis the characteristic findings of basal cell carcinoma are described as below:
• Basal cell carcinoma pathological features mainly depend upon the subtype. The following table summarizes them:^[6][7]

Subtypes of BCC	Gross features		Microscopic features
	Findings	Images	Findings	Images
Nodular	Shiny, pearly papule or nodule with a smooth surface Rolled borders and telangiectasias Mostly seen on the head and neck		Discrete nests of malignant basaloid cells in the dermis Peripheral palisading Mucoid stroma containing plump spindle cells
Superficial	Well-circumscribed Erythematous thin plaque or patch with scale Central clearing and thin rolled borders Most common on the trunk		Multiple lobular foci of basaloid palisading keratinocyte tumors These are usually attached superficially to the epidermis with a myxoid stroma and band-like lichenoid infiltrate
Infundibulocystic	Well-circumscribed pearly papule Most common on the head and neck region		Well-circumscribed Anastomosing strands of basaloid cells and scattered infundibulum-like cystic structures
Fibroepithelial	Skin-colored/erythematous Sessile plaque/pedunculated papulonodule They have a predilection for trunk region		Multiple collections of delicate strands of epidermal basaloid keratinocytes These are usually arranged in a reticular pattern within a spindle cell stroma
Morpheaform	Infiltrated plaque with poorly defined borders and shiny surface Most common on head and neck region		Thin cords of basaloid cells surrounded by a sclerotic collagenous stroma Absent peripheral palisading and stromal cleft formation Positive staining of tumor stroma with smooth muscle alpha-actin
Infiltrative	Poorly defined Indurated, flat or depressed plaque with white, yellow, or pale pink color They may have overlying crusts, erosions, ulcerations, or papules		Thin cords with angulated ends of few basaloid keratinocytes Usually embedded in a classic mucinous/myxoid stroma
Micronodular	Erythematous macule or thin papule/plaque		Multiple small aggregates of basaloid cells within the dermis, with subtle peripheral palisading and retraction artifact
Basosquamous	Majority found on the head and neck		Well-defined nodular or superficial BCC component overlying an invasive front showing basal cell carcinoma and squamous cell carcinoma histologic feature

{{#ev:youtube|JnJXrFnvOKs}}

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D., Maneesha Nandimandalam, M.B.B.S.[2]

Although the exact causes were unknown, the following are some of the factors that have been associated with the development of basal cell carcinoma: radiation exposure, gene mutations, xeroderma pigmentosa, epidermodysplastic verruciformis, nevoid basal cell carcinoma syndrome, bazex syndrome, rombo syndrome etc.

Although the exact cause is unknown, there are some environmental and genetic factors that may predispose to basal cell carcinoma.

The following table summarizes the causes of basal cell carcinoma (BCC):

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D.

Basal cell carcinoma must be differentiated from other common causes of skin lesions, such as squamous cell carcinoma, microcystic adnexal carcinoma, trichoepithelioma/trichoblastoma, and merkel cell carcinoma.

The following table summarizes common differential diagnosis for basal cell carcinoma :^[1]

The following table summarizes other differential diagnosis for basal cell carcinoma:

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2], Saarah T. Alkhairy, M.D.

The annual incidence of basal cell carcinoma in the United States is approximately 2.8 million which increases with increasing age. Men and white skinned people are affected relatively more, especially in states closer to the equator.

• The annual incidence of basal cell carcinoma in the United States is approximately 2.8 million.^[1]

• The incidence of basal cell carcinoma increases with age.^[2]
• The incidence rate doubles from 40 to 70 years of age.
• The incidence rate for those aged below 40 years is also increasing.

• Although both are affected, the incidence in males>females.^[3]
• This can be explained by gender differences in sun exposure habits and awareness of skin conditions.
• Men are also less likely to seek medical attention, allowing the more advanced development of skin cancer in comparison with women.

• Although it is observed in all races, dark skinned people are less commonly affected than fair skinned ones.
• Whites of celtic ancestry have the highest risk for basal cell cancer.
• Incidence is low in blacks, Asians, and Hispanics

• States closer to the equator, such as Hawaii and California, have a higher incidence of basal cell carcinoma compared to midwestern states^[4][5]

• An increasing incidence over time has also been noted in other countries, such as Canada, Finland, and Australia^[6][7][8]
• Basal cell carcinoma (BCC) is the most common skin cancer among the Far-east Asian race^[9]
• Majority of Far-east Asian race are Chinese (44.2%), Malays (32.6%), Bidayuhs (14.0%), and Ibans (6.9%)^[9]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2], Saarah T. Alkhairy, M.D.

Environmental and genetic risk factors that may predispose to basal cell carcinoma include radiation exposure, physical characteristics, gender, albinism, xeroderma pigmentosum, epidermodysplastic verruciformis, nevoid basal cell carcinoma syndrome, bazex syndrome, rombo syndrome etc.

• There are some environmental and genetic risk factors that may predispose to basal cell carcinoma.^[1][2][3]

• The following table summarizes the causes of basal cell carcinoma (BCC):

• Other risk factors for the development of basal cell carcinoma are the following^[1][2]:
  • Current immunosuppressive therapy after organ transplantation
  • Arsenic exposure for a long time
  • Personal history of skin cancer
  • Two or more first-degree relatives with melanoma
  • Total of 100 nevi or at least five atypical (dysplastic) nevi
  • More than 250 treatments with psoralen plus ultraviolet A (UVA) therapy for psoriasis
  • Radiation therapy for cancer as a child
  • Oral contraceptive pills intake
  • Rheumatoid arthritis is also associated with increased risk for basal cell cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D., Maneesha Nandimandalam, M.B.B.S.[2]

The U.S. Preventive Services Task Force has found no evidence to recommend for or against screening. The American Cancer Society recommends that a health care provider examine the skin every year if the patient is older than 40 years, and every 3 years if the patient is between 20-40 years.

• The U.S Preventive Task Force has found no evidence to recommend for or against screening^[1].

• Task Force members state that “clinicians should remain alert for skin lesions with malignant features noted in the context of physical examinations performed for other purposes,” and recognize that “even without formal screening programs, mortality from basal cell and squamous cell carcinoma is low compared with mortality from melanoma, but early detection and treatment may reduce morbidity and disfigurement from these cancers.”

• The American Cancer Society recommends that a health care provider examine the skin every year if the patient is older than 40 years, and every 3 years if the patient is between 20-40 years

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2] Saarah T. Alkhairy, M.D.

It is a slow-growing locally invasive lesion with an unlikely risk of metastasis. Most patients are often asymptomatic. The major complication is its recurrence and involvement of surrounding structures. With appropriate treatment, the prognosis is usually excellent.

• Patients with basal cell carcinoma are often asymptomatic^[1]
• They often report a slowly enlarging lesion which does not heal and bleeds when traumatized
• It is locally invasive and destructive so the name rodent cancer
• The overall risk of metastases is estimated to be less than 0.1%
• The risk of invasion and recurrence is based on size, duration, location and subtype (sclerodermiform/morpheaform and micronodular clinical variants have a higher risk)
• Even without a recurrence, a personal history of basal cell carcinoma increases the risk of developing all types of skin cancers

• The main complication of basal cell carcinoma is recurrence.^[2][3]
• The following are the factors associated with increased risk of basal cell carcinoma recurrence:
  • Location and size
    • >/= 6 mm in diameter in high-risk areas (eg, central face, nose, lips, eyelids, eyebrows, periorbital skin, chin, mandible, ears, preauricular and postauricular areas, temples, hands, feet)
    • 10 mm in diameter in other areas of the head and neck
    • 20 mm in diameter in all other areas (excluding hands and feet)
  • Aggressive pathologic variants
    • Morpheaform, sclerosing, or mixed infiltrative
    • Micronodular
    • Basosquamous
  • Lesions in sites of prior radiation therapy (RT)
  • Lesions with poorly defined borders
  • Lesions in immunocompromised patients
  • Perineural invasion

• Prognosis of basal cell carcinoma is usually excellent.^[4][5]
• These lesions are typically slow growing, and metastatic disease is a very rare event.
• Basal cell carcinoma will cause considerable disfigurement by locally destroying skin, cartilage, and even bone.
• Recurrence is a issue with basal cell carcinoma.
• Approximately 50% of recurrences are apparent within the first two years.

Template:WikiDoc Sources