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Basal cell carcinoma

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Most common cancer in the world with 2.8 million cases per year in the U.S.

Accounts for approximately 25% of all diagnosed cancers in the US.

Its  incidence exceeds that of all other cancers combined.

In White populations, one in five people will develop a basal cell carcinoma.

Often occurs in fair-skinned people over age 40 who have been exposed to large amounts of ultraviolet radiation during their lifetime.

Fair skin, red or blonde hair, and light eyecolor associated with BCC and are independent risk factors due to greater susceptibility to UV damage.

Most basal cell tumors develop on skin sites exposed to radiation, either from the sun or from therapy.

Constitutes approximately 75-80% of nonmelanoma skin cancer.

Squamous cell carcinoma has half the incidence.

Annual global incidence of nonmelanoma skin cancers is 2-3,000,000, and approximately 80% of these are basal cell carcinomas.

Overall incidence is increasing significantly, and is associated with marked geographic variation.

Highest incidence rate is in Australia, with one to 2% per year reporting rate.

Most commonly diagnosed malignancy worldwide.

Develops in the basal layer of the epidermis.

Average lifetime risk for Caucasians is 5-30%, depending in large part on skin type and patterns of sun exposure.

Induced by UV-B exposure and may occur at sites of previous trauma such as scars and burns.

Sun exposure and fair skin are primary risk factors.

Male predominance and mean onset seventh decade of life.

Australia with highest rate in the world with a incidence of up to 2% per year.

In the U.S. yearly estimated rates 407 cases per 100,000 white men and 212 cases per 100,000 white women.

Incidence of metastatic disease is low : between 0.0028% and 0.5% with more than 80% of these originating from head and neck primary basal cell carcinomas.

BCCs that develop in the head and neck area are more likely to recurrent those that develop on the trunk and extremities.

BCCsor more likely to recur when lesions are 6 mm or greater in diameter.

BCC can produce substantial local tissue destruction along with disfigurement, and may involve extensive areas of soft tissue, cartilage, and bone.

Highest rates in elderly white men.

Most cases occur in people aged 65 years and older.

Number of cases more than doubled in last 20 years, but deaths very low.

Increased incidence in basal nevus syndrome, xeroderma pigmentosum and albinism.

Factors in tumor development include: ultraviolet light, PUVA therapy, radiation exposure, arsenic exposure, scars and immunosuppression.

A major cause is exposure to ultraviolet radiation, which leads to cumulative DNA damage and acquired gene mutations.

Settings of immunosuppression, such as organ transplantation, long-term use of psoralen and UV light increase the incidence of BCC.

BCC  incidence is approximately 5 to 10 fold higher in organ transplant patients, than in the general population.

Most sporadic cases arise from chronic sun exposure.

Relationship with sun exposure is non-linear and intermittent intense sun exposure may be a stronger determinant.

Occur in sun exposed sites.

80% occur in the head and neck, 15% on the trunk common 5% arms, legs or other sites.

Increased incidence p53 clones.

Abnormal activation of the hedgehog signaling pathway present in most cases resulting in increased proliferation of basal cells.

Mutations in the PTCH 1 gene on chromosome 9Q and mutations in the tumor suppressor gene p53 are common events in BCC development.

Certain genetic syndromes greatly predispose affected individuals to skin cancers, including BCC, such as albinism and xeroderma pigmentosum, in which affects in UV light induced unscheduled DNA repair exists.

The most common form of lesion is nodular basal cell carcinoma.

Nodular basal cell carcinoma presents as a pearly white or pink nodule, and as ot grows it may develop a slightly elevated rim with a flattened smooth or ulcerated center.

Histologically, aggressive growth patterns, include micronodular, infiltrative, sclerosing, and morphea form lesions, are more likely to recur than nodular and superficial BCC.

Basosquamous, carcinomas have histologic appearance of both BCC and squamous cell carcinoma, and have a greater metastatic potential than BCC.

Loss of function mutations occur in protein patched homologue 1 (PTCH1), which acts as a tumor suppressor protein that inhibits smoothened homologue, a downstream protein in the hedgehog signaling pathway.

Slow growing.

Metastasis are rare and develop in 0.028-0.55% of cases.

Classified into three subtypes:nodular, accounting for 60% of cases and occurs frequently in sun exposed areas of the head and presents is a papule or nodule, superficial accounting for 30% of cases and occur most frequently in the trunk characterized by small buds of basaloid tumor cells extending from the epidermis and other, accounting for10% of cases and may be sclerosing or fibrosing basal cell carcinomas or have ill-defined borders making complete excision difficult.

Diagnosis – guidelines recommend punch biopsy to guide the decision on optimal treatment.

It is important to distinguish between basal cell carcinoma and non-basal cell carcinoma lesions in to determine the histopathological subtype.

For a superficial basal cell carcinoma, topical therapy might be prescribed, however for non-superficial BCC, the width of resection margins or an indication for Mohs’ micrographic surgery is based on the subtype.

Optical coherence tomography (OCT) is a noninvasive tool for a basal cell carcinoma diagnosis which can generate real time, cross-sectional imaging of tissue micro architecture with a depth of 1 to 1.5 mm: it is not inferior to regular care punch biopsy.

in 66% of patients biopsy could be avoided, minimizing treatment delay in avoiding an invasive procedure (Patty, F-A).

Prevention is the major aspect of management.

More than 100,000 BCCs treated each year in patients who ultimately die within 1year.

Some lesions can be symptomatic with ulcerations, can threaten eyelids, ears, cause pain, itching, or bleeding and occur in about 12% of BCC patients.

Elderly patients are at highest risk of treatment associated harm including cancer anxiety, fear of metastases or recurrence, and adverse effects from treatment.

Surgical treatment the major therapy.

Surgical excision is the most common treatment with a high success rate.

Surgical margins should be about 4 mm.

Surgery can be debilitating, and disfiguring and non surgical approaches may be required with the use of radiotherapy, photodynamic therapy, chemotherapy, and topical therapy as alternatives.

Surgical excision cure rate is greater than 95%, as is curettage and cautery, cryosurgery, and Moh’s micrographic surgery.

Curettage and electro dissection electrodessocation does not allow for histologic margin assessment.

Curettage and electrodesiccation is effective for superficial lesions.

Curettage and electrodesiccation Should not be used in areas with terminal hair, growth-scalp, pubic, and axillary regions, or beard due to the risk that tumor extends down to follicular structures.

Mohs surgery the gold standard for treatment of the more aggressive subtypes of basal cell cancer.

Mohs surgery is appropriate for the majority of basal cell carcinomas, although it is designated inappropriate in certain forms and subtypes of patients: low risk subtypes including recurrent superficial and primary nodular basal cell carcinoma when located on the trunk and extremities excluding pretibial surfaces, hands, feet, nails and ankles.

Mohs surgery takes about three times as long as conventional excision, with a mean procedure length of time three hours versus one hour for conventional surgery.

Recurrence rate for field therapies range from 3-8%.

Margins have been suggested to be 2 to 4 mm for low risk, well demarcated tumors smaller than 2 cm, whereas margins of forward to 6 mm-8 millimeters for high risk lesions: margins required for completely excision of 95% of tumor.

High-risk lesions include those with incompletely excised basal cell carcinomas, primary lesions with clinically indistinct borders, lesion of high risk areas which includes eyelids, nose, ears, nasolabial fold, upper lip, vermillion border, columella, periorbital region, temples, preauricular and postauricular areas and scalp, lesions involving cosmetically and functionally important areas such as the face, genitals, anal and perianal regions, hands and feet, and nail you need to areas, tumors with aggressive behavior that is growing rapidly or greater than 2 cm in size, tumors with aggressive histology including sclerosing, basosquamous, perineural, periappendageal, peri vascular, infiltrating, adenoidal, or multicentric, tumors that develop insights that had been previously irradiated, and tumors that develop in immunosuppressed patients.

Shave removal of epidermal and dermal lesions, without including fat, and does not require suture closure, but is a concern for an accurate margin status.

Shave removal for low risk basal cell carcinomas are recommended for lesions in the trunk or extremities, with a 0.5 to 30% rate of recurrence over 3 to 5 year follow up.

Following surgery, if margins are positive patients may undergo Moh’s surgery, or radiation therapy.

Imiquimod has an 83% complete clinical and histopathologic clearing of tumor.

Erivedge (vismodegib) indicated for the treatment of adults with metastatic basal cell cancer, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Radiation is consideration for patients as primary therapy for non-surgical candidates for both both low risk and high risk disease and in patients with advanced basal cell carcinoma, locally advanced, with nodal and metastatic lesions.

RT as additional therapy in low risk basal cell carcinoma after positive margins occurs with standard excision.

Radiation therapy is also recommended for high risk BCC as additional treatment after standard excision, or other forms of therapy with positive margins and adjuvant treatment after negative margins in case of extensive perineural or large nerve involvement.

Metanalysis report five year recurrence rates of 8.7 and 9.8% after RT on primary and recurrent BCC, respectively.

In a randomized study of patients to receive either surgery with standard excision with free margins of 2 mm or more, or RT as primary treatment of BCC had a higher recurrence rate with RT than surgery 7.5% versus 0.7%, with poorer cosmetic outcomes, and more postoperative complications.

In patients with superficial BCC topical therapy with imiquimod, 5FU, photodynamic therapy or cryotherapy can be considered, although cure rates are approximately 10% lower than for surgical treatment.

The  overall treatment success withimiquimod is 78 to 80% with superficial BCC.

Cosmetic outcomes by dermatological assessment is significantly better with imiquimod than surgery.

Topical 5FU has a five-year tumor free survival probability of 70% to 90%  for superficial BCC.

The treatment of actinic keratoses with nicotinamide reduces the occurrence new basal cell cancers by 20% at a 12 month follow up.

 

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