Skin cancer causes

Risk factors for basal and squamous cell skin cancers are strikingly similar. These lesions, although seen in younger age groups, are most often encountered in patients 60 years of age or older.
The mechanism by which ultraviolet rays cause sun-damaged skin has been extensively studied. Laboratory experiments indicate that the wavelengths with the most potential for carcinogenesis are those in the range of 280 to 320 nm, the ultraviolet B band. This ultraviolet B is responsible for the common sunburn. The transition from normal to actinic (i.e., sun damaged) to cancerous skin is usually a progressive process that occurs over several decades.
With the current environmental changes occurring with the earth's protective ozone layer, the concern for skin cancer becomes much more significant. A dramatic ozone depletion above the Antarctic continent has been detected. For each 1% reduction in atmospheric ozone concentration, there is a concomitant 2% increase in ultraviolet B penetration.
The carcinogenesis of epidermal tumors parallels the multistep development of other tumors. As with other tumors, certain characteristics render the host more susceptible to the development of cancer. Traits that are associated with an increased incidence of skin cancer include fair complexion, rays hair, blue or green eyes, inability to tan, propensity to sunburn, history of multiple or severe sunburns, and Celtic ancestry. Other factors implicated include age, occupation, habits (tanning booths), and residential geography, which are considered indirect causes of increased sun exposure.
The bulbs used in tanning booths are almost exclusively ultraviolet A wavelength and are promoted as providing a safe suntan. However, recent evidence indicates that ultraviolet A (320 to 400 nm) synergistically augments ultraviolet B responses and is independently capable of producing deleterious skin alterations and carcinogenesis.
Other etiologic factors are associated with the development of skin cancer. Chronic exposure to chemical agents, such as arsenic in patients treated with Fowlers solution, has been associated with the development of multiple squamous and basal cell tumors. Patients with chronic ra-diodermatitis, resulting from superficial Radiotherapy, demonstrate a propensity to develop multiple and aggressive lesions. Trauma in the form of burns, ulcers, and scars is also associated with the development of skin cancer (i.e., Marjolins ulcer). Immunosuppression, common in transplant patients and patients with leukemia or lymphoma, can be complicated by an increased incidence or aggressiveness of skin cancers .
Studies of human papilloma virus offer additional support for the importance of immune dysfunction in the development of skin squamous cell skin cancer. One study showed human papilloma virus presence in 60% of skin squamous cell skin cancer lesions found in renal autograft recipients. Moreover, this human papillomavirus presence was significantly higher than that found in matched transplant recipients without skin cancer. There also appears to be a high incidence of human papillomavirus in squamous cell skin cancer lesions of the cervix, penis, and digits.
Genetic syndromes, such as xeroderma pigmentosum (autosomal recessive) and nevoid basal cell skin cancer syndrome (autosomal dominant), are associated with a predilection for developing multiple basal cell skin cancers, often at an early age.

What is Basal cell carcinoma

Basal cell carcinoma is the commonest malignant tumor affecting the skin. Clinically, it is a slow-growing locally invasive and locally destructive tumor in which distant metastases rarely occur. Several types are described based on their physical appearance, and there are a variety of clinical classifications. The essential component determined by clinical investigation is the extent of the tumor. Localized tumors generally have a clear cut-off point from tumor to normal tissue and the margins can be well defined. The papulonodular variety fits the classical description of the rodent ulcer with a rolled, pearly edge which often develops central ulceration. The solid type almost appears to grow out of the skin in an exophytic way and frequently has telangiatatic vessels coursing across its surface. The cystic variety can appear as a thin cyst, particularly around the eyelids, and sometimes also has telangiatatic vessels.

In the diffuse type, the pattern of spread is insidious, and defining the tumor margins can be difficult. The infiltrating type is clearly not purely an exophytic growth and infiltration of adjacent tissues can be demonstrated by palpation. The multifocal variety appears to have areas of almost normal looking skin which may represent healing of a previously ulcerated area. These multifocal lesions may be superficial or can infiltrate in depth. The morphoeic type of basal cell carcinoma infiltrates the dermis and produces a dense stromal reaction with stromal fibrosis. This gives the skin a characteristic white plaque-like appearance which is stiff, hence the term morphoea. The difficulty lies in determining the lateral extent of these tumors because of the dense stromal reaction. Metatypical basal cell carcinomas commonly appear as large, ulcerating, often exophytic, lesions. Characteristically they look very similar to squamous cell carcinomas but have a long history. It is the length of history that usually differentiates these tumors. Patients may present with more than one primary basal cell carcinoma which may be associated with a syndrome as discussed previously. Patients who have a basal cell carcinoma show a high incidence of a second lesion compared with the normal population. Second basal cell carcinomas frequently develop in the first year (16 per cent) and the incidence then falls to approximately 10 per cent over the next 4 years.
In addition to the physical appearance of primary basal cell carcinoma, there are three other clinical pictures which are encountered, namely recurrent basal cell carcinoma, aggressive or horrifying basal cell carcinoma, and metastatic basal cell carcinoma.

Recurrent basal cell carcinoma
The clinical appearance of recurrent basal cell carcinoma is very variable and is often dependent on previous treatment. The margins are difficult to determine but recurrence should always be regarded as having a diffuse pattern. Patients at risk of developing recurrence include those who have already presented with recurrent basal cell carcinoma, those with basal cell carcinomas showing an aggressive histological pattern, and lesions arising at cosmetically sensitive sites where tissue is scarce.

Horrifying basal cell carcinoma
This is the most dangerous basal cell carcinoma, characterized clinically by deep invasion and widespread destruction of adjacent tissues. The terminology is somewhat confusing, since it is also termed aggressive basal cell carcinoma, but this latter term applies to the histological appearance rather than the clinical appearance and behaviour. These tumors tend to occur in young individuals; they are large (more than 3 cm) and often appear in the region of the head and neck, particularly the scalp. Inadequate primary treatment is cited as an important factor in the development of horrifying basal cell carcinoma, particularly deep tumor extension following radiotherapy. The diffuse infiltrative type of basal cell carcinoma has been implicated in the development of these horrifying lesions, with a high incidence in morphoeic or metatypical basal cell carcinomas and those with adenoid differentiation. Unusual aetiologies such as arsenic, immuosuppression, and X-ray-induced tumors have also been implicated.
The clinical danger of these tumors, particularly those arising in the head and neck, is their capacity to infiltrate through bone and into the central nervous system causing widespread local destruction.

Metastatic basal cell carcinoma
The development of a distant metastasis from a basal cell carcinoma is exceptionally rare, so much so that it remains worthy of a single case report. The incidence is reported as varying from 0.0028 per cent to 0.55 per cent. Characteristically, patients have a large basal cell carcinoma, usually of long standing, which has proved resistant to treatment at the local site. Metatypical basal cell carcinoma with squamous differentiation has been associated with metastases. Facial basal cell carcinomas tend to metastasize to regional nodes, but a wide variety of organs have also been reported as showing metastasis including lung, liver, brain, heart, and pericardium. The histological variations that occur in basal cell carcinoma continue to fuel the debate as to whether basal cell carcinomas do indeed metastasize or whether these tumors are variants of adnexal tumors.

Pathological features
One of the major problems with basal cell carcinoma is that the cell of origin and the histiogenesis have not been accurately determined. The keratin phenotype of basal cell carcinoma would suggest an origin in the hair follicles. If this is indeed the case, then basal cell carcinoma is a type of adnexal tumor; however, because of its frequent occurrence it has been classified separately. Unlike many other tumors there does not appear to be a premalignant phase for basal cell carcinoma arising de novo. Basal cell carcinomas are composed of islands or nests of basophilic cells which resemble miniature basal cells of the epidermis lying in a connective tissue stroma. Typically the cells pack together in a regular manner to produce peripheral palisading. The cellular islands and nests within the stroma give them different patterns, and this has led to a variety of classifications. From the clinical perspective, it is the pattern and degree of infiltration and the arrangement of cells within the stroma that is most important rather than the degree of differentiation or number of mitoses present.

Squamous cell carcinoma : SCC

Skin cancer ---> Non melanoma skin cancer ---> squamous cell carcinoma

Squamous cell carcinoma is a malignant invasive proliferation of epidermal keratinocytes.
Epidemiology
Squamous cell carcinoma is the second most common type of skin cancer. It is more common in men and in the elderly population.
Pathology
There is a relationship with chronic ultraviolet exposure. Squamous cell carcinoma is especially common in individuals with skin phototypes I and II. Other etiological factors include topical and systemic carcinogens such as arsenic, photochemotherapy (PUVA) and chronic immunosuppression (following allogeneic organ transplantation or in those with lymphoma or leukemia). The lesions may also arise at sites of long-standing radiation dermatitis, scarring (discoid lupus erythematosus), ulceration and pre-existing lesions such as Bowen's disease. Some squamous cell carcinomas are associated with human papillomavirus infection. Smoking is associated with lesions on the lip.
Scope of disease
Squamous cell carcinoma is locally invasive and has the potential to metastasize to lymph nodes and other organs of the body.
Clinical features
Squamous cell carcinoma usually presents as an expanding plaque or nodule with an ill-defined, indurated base and surface crusting. The lesion may ulcerate. It is most often seen on sun-exposed sites (face, neck, forearms and dorsum of hands) in association with solar elastosis and multiple actinic keratoses. Local lymph nodes may be enlarged with metastatic involvement.
Investigations
Skin biopsy
A skin biopsy is required to establish a histopathological diagnosis and to gain information on the degree of differentiation, grade, depth and level of dermal invasion, the presence of perineural, vascular or lymphatic invasion, and clearance margins of the excised tissue.
Lymph node biopsies
Squamous cell carcinomas usually spread to local lymph nodes; therefore clinically enlarged nodes should be excised and submitted for histopathological analysis.
Initial management
Patient education
Sun avoidance, the use of sunscreen and protective clothing are the main steps in the prevention of actinic keratosis and further squamous cell carcinomas, particularly in patients receiving immunosuppression.
Multidisciplinary team approach
There is overlap between dermatologists, clinical oncologists and plastic surgeons in the management of patients with squamous cell carcinoma, and therefore a multidisciplinary approach is favored.
Surgical management
Curettage and cautery
Curettage and cautery may be feasible treatment options for small, well-defined, low-risk tumors.
Excision biopsy and regional node dissection
Surgical excision or Mohs' micrographic surgery is the treatment of choice for the majority of lesions. For low-risk tumors (less than 2 cm in diameter), excision with a 4 mm margin is expected to achieve complete cure in 95%.
Mohs' micrographic surgery is indicated for larger, higher-risk tumors. With this technique, each section is examined with frozen section analysis to determine the completeness of resection. It is particularly useful in difficult sites where wide surgical margins may be technically difficult to achieve without functional impairment.
Tumor-positive lymph nodes are usually managed by regional node dissection.
Medical management
Radiotherapy
Other treatment options include radiotherapy for non-resectable tumors or lymph node disease.
Prognosis
Squamous cell carcinoma has an overall remission rate after therapy of 90%. The factors that influence metastatic potential include anatomical site, tumor size, degree of differentiation and immunosuppression. Tumors arising in areas of radiation injury, chronic inflammation or chronic ulcers have the highest metastatic potential when compared to those from sun-exposed sites. Tumors more than 2 cm in diameter are 3 times as likely to metastasize compared to smaller tumors. Tumors more than 4 mm in depth or extending down to the subcutaneous tissue are more likely to recur and metastasize compared to thinner tumors. Poorer prognosis is associated with less well differentiated tumors, and tumors arising in patients who are immunosuppressed.

Squamous Cell Carcinoma: SCC

Skin cancer ---> Non melanoma skin cancer ---> squamous cell carcinoma

SCC is the second most common form of skin cancer and is derived from the epithelial keratinocyte. SCC can deeply invade surrounding structures and metastasizes most commonly to regional lymph nodes. In immunosuppressed transplant individuals, SCC is the most common skin cancer, occurring 65 to 250 times more frequently than in the general population. SCC in these individuals tends to have more aggressive behavior.
Several precursor lesions to invasive SCC exist, most commonly actinic keratosis and Bowen's disease (in situ SCC). Erythroplasia of Queyrat, another precursor lesion, represents SCC in situ on the glans penis. Histologically, SCC shows malignant degeneration of epithelial cells with differentiation toward keratin formation. SCC often appears clinically as a non healing sore with ulceration and inflammatory pink borders or an erythematous papulonodule with overlying keratotic crust or ulceration. These tumors most often arise in chronically actinically damaged skin or within an actinic keratosis, but they may also develop in burn scars or chronic inflammatory wounds. These lesions may infiltrate widely. Metastasis to regional lymph nodes accounts for approximately 80% to 90% of metastatic cases. Distant sites, such as lung, liver, brain, bone, and skin, account for the other 10% to 20%. Metastatic SCC portends a poor prognosis with a 10-year survival rate for regional lymph node disease of less than 20% and for distant disease of 10%.
Accurate assessment of the higher-risk cutaneous SCCs is handicapped because of the lack of large prospective studies using multivariate analysis. Nine variables, however, have been identified as prognostic risk factors by retrospective analysis.

Etiology of BCC and SCC

Surgical Treatment of Nonmelanoma Skin Cancers

Adjuvant and Primary Radiation Therapy for nonmelanoma cancers

Basal cell carcinoma : BCC

Skin cancer ---> Non melanoma skin cancer ---> Basal cell carcinoma

Basal cell carcinoma (rodent ulcer) is a slow-growing, locally invasive tumor with virtually no capacity to metastasize.
Epidemiology
Basal cell carcinoma is the most common type of skin cancer, approximately 4 times more common than squamous cell carcinoma.
Pathology
The most significant etiological factor is chronic excess ultraviolet radiation exposure. As a result, exposed areas such as the head and neck are most commonly involved. Other risk factors include increasing age, male gender, and skin phototypes I and II. Histologically there is a proliferation of atypical basal keratinocytes.
Clinical features
The clinical appearances and morphology are diverse and include nodular, morphoeic, superficial multifocal, keratotic and pigmented varieties.
The nodular basal cell carcinoma tends to arise on the forehead, nose or adjacent to the inner canthus of the eye as a skin-colored or pigmented, translucent nodule with surface telangiectasia. Gradual enlargement leads to central ulceration (ulcerated basal cell carcinoma) with a peripheral, 'rolled' pearly edge. There may also be cystic change (cystic or nodulocystic basal cell carcinoma). The morphoeic (sclerosing) basal cell carcinoma presents as a firm, indurated, skin-colored, scar-like plaque with ill-defined edges, commonly on the nasolabial fold or forehead. Superficial multifocal basal cell carcinomas tend to arise on extra-facial sites as red, scaly plaques and have no relation to sun exposure. Pigmented basal cell carcinomas may be brown, blue or black with a smooth glistening surface. Keratotic basal cell carcinomas have evidence of keratinization on histology.
Initial investigations
Skin biopsy
A skin biopsy confirms the diagnosis and determines the histological subtype. Alternatively, cytology can be performed on skin scrapings.
Initial management
Multidisciplinary team approach
Depending on the size and site of the basal cell carcinoma, dermatologists, clinical oncologists and plastic surgeons may all be involved in the management. Therefore, a multidisciplinary approach is favored.
Surgical management
Curettage and cautery
Curettage and cautery is a suitable option for patients with low-risk lesions (small, well-defined, primary lesion) and can achieve 5-year cure rates of up to 97%. Patients with recurrent morphoeic tumors in high-risk sites such as the nose, nasolabial folds and around the eyes should undergo formal surgical excision.
Cryotherapy
Cryotherapy can be used on low-risk lesions with non-aggressive histology that are not recurrent lesions.
Surgical excision
The main aim of surgery is complete excision with a clear surgical margin.
Medical management
Radiotherapy
Radiotherapy is useful for treatment of basal cell carcinoma in locations where disfigurement results from surgical excision (although atrophy telangiectasia may develop in the long term and affect the cosmetic results). The 5-year cure is approximately 90%. Patients with recurrent lesions after radiotherapy should undergo surgical excision.
Topical 5-fluorouracil
Topical 5-fluorouracil is usually the treatment of choice for multiple superficial basal cell carcinomas on the trunk and lower limbs.
Palliative management options
Aggressive treatment can be inappropriate in elderly debilitated patients, especially for asymptomatic low-risk lesions. Palliative treatment such as debulking the tumor or radiotherapy may be more appropriate.
RECENT ADVANCES
Intralesional interferon and photodynamic therapy are still under investigation with some early promising results.
Prognosis
Metastasis is extremely rare and the morbidity is related to local tissue invasion and destruction. Patients with a single tumor are at a significant increased risk of developing subsequent basal cell carcinomas.

Basal Cell Carcinoma: BCC

Skin cancer ---> Non melanoma skin cancer ---> Basal cell carcinoma

BCC is the most common form of skin cancer. These epithelial- derived tumors can be divided into various subtypes according to clinical appearance, histologic pattern, and biologic behavior. Although BCCs rarely metastasize, they are characterized by slow but relentless and destructive local invasion that results in high morbidity without treatment. The subclinical local invasion may be deep, extensive, and asymmetric, with finger like extensions several centimeters beyond the clinical borders.
The most common subtype of BCC is the well-circumscribed nodular variety. These tumors often present as pearly papules or nodules with telangiectases. They may be pruritic and bleed occasionally. With time, the center ulcerates to create peripheral rolled borders; such ulcerating BCCs are called rodent ulcers. Occasionally, the lesions are deeply pigmented and nodular and can be confused with melanoma. This variant has been called a pigmented BCC. The histologic features of these tumors demonstrate isolated areas of basaloid tumor islands arising from the epidermis with peripheral palisading of nuclei and stromal retraction. In some cases, the BCC has histologic features of squamous metaplasia with keratinization. These tumors have basosquamous differentiation and can become more aggressive and develop regional lymphatic spread.
The most locally aggressive type of BCC is characterized by a diagnostic histopathologic aggressive growth pattern, known as morpheaform, sclerosing, or fibrosing BCC. Clinically, these tumors may be more subclinical, are flat, and appear to be scar like. They have a significant incidence of recurrence because of the isolated, finger like fronds of basal cell tumor cells that may deeply invade the surrounding structures well beyond the clinical margins of the lesion. These small, finger like islands are often missed with standard histologic margin control.
Clinically, superficial BCCs are scaly pink to red lesions. Frequently, they are confused with psoriasis or other eczematous, scaly dermatoses. Although these tumors are usually relatively superficial, extensive superficial subclinical involvement is common. Numerous risk factors are associated with possible extensive subclinical invasion and increased rates of local recurrence for BCC after standard treatment, including surgical excision

Causes of BCC and SCC

Non melanoma skin cancer ---> Causes of Non melanoma skin cancer

Both BCC and SCC are most commonly induced by significant exposure to ultraviolet light from the sun or tanning booths. These cancers are the predominant neoplasms on the head, neck, trunk, lower legs, and extensor arms and hands where sun exposure is common. Skin cancer is a significant occupational hazard for people who work outdoors. The phenotype at increased risk is one with fair skin who sunburns and freckles easily, blue eyes, and red or blonde hair. Melanin pigment in the skin appears to be the protective factor.
A number of genetic syndromes are associated with an increased risk of developing NMSC, including Gorlin syndrome, xeroderma pigmentosa, and albinism. Gorlin syndrome is an autosomal dominant disorder associated with multiple BCCs, palmoplantar pits, jaw cysts, frontal bossing, and hypertelorism. Albinism is a disorder characterized by a partial or complete deficiency in melanin production and, thus, loss of protective pigment. Another factor associated with NMSC, primarily SCC, is chronic exposure to chemicals such as arsenic and hydrocarbons (found in coal tars, soot, and asphalt). Cigarette smoking has been associated with SCC of the lip and mouth. Human papillomavirus has been associated with cutaneous SCC in the genital and acral/periungual areas. Radiation has been associated with both SCC and BCC.

Adjuvant and Primary Radiation Therapy for nonmelanoma cancers

Non melanoma skin cancer ---> treatment of Non melanoma skin cancer ---> Radiation therapy

Radiation therapy may be useful for primary treatment of low-risk non melanoma skin cancers. In experienced hands, primary radiation therapy may also be useful for higher risk tumors with high cure rates. For cutaneous SCC with many high-risk factors and for those with extensive neurotropism, adjuvant prophylactic radiation therapy to the primary site and the primary draining lymph nodes may decrease the risks of local recurrence and regional nodal metastasis. Prophylactic adjuvant radiation therapy should also be considered for highly aggressive, deeply invasive BCCs that exhibit extensive neurotropism.

Treating BCC and SCC (Skin Cancer #6)

Skin cancer awareness ---> skin cancer videos ---> Non melanoma skin cancer ---> treatment of Non melanoma skin cancer

Basal cell carcinoma and squamous cell carcinoma are the two types of non-melanoma skin cancers. Luckily, there are many options for treating them.

Surgical Treatment of Nonmelanoma Skin Cancers

Non melanoma skin cancer ---> treatment of Non melanoma skin cancer ---> Non melanoma skin cancer Surgery

A skin biopsy for diagnosis is important before treatment of any skin cancer. Fortunately, most non melanoma skin cancers are small, low-risk lesions that respond with 90% to 95% cure rates to standard treatment techniques, including curettage and electrodesiccation, cryosurgery, radiation therapy, and surgical resection. Many skin cancers can be removed with elliptical excisions. Margins for low-risk SCC range from 0.5 to 1 cm. Margins for low-risk BCC range from 0.3 to 0.5 cm. Mohs surgery should be considered for BCCs and SCCs that exhibit the higher-risk factors. If Mohs surgery is not available, excision with careful frozen-section control (with permanent section confirmation) is indicated. The fundamental oncologic principle of tumor clearance first, reconstruction second should be followed.

Understanding Basal Cell Carcinoma (Skin Cancer #4)

Skin cancer awareness ---> skin cancer videos ---> Non melanoma skin cancer ---> Basal Cell Carcinoma

Basal cell carcinoma is the most common form of all cancers. Learn more about BCC.

Mohs Surgery

Non melanoma skin cancer ---> treatment of Non melanoma skin cancer ---> Non melanoma skin cancer Surgery ---> Mohs Surgery

Mohs surgery was developed by Frederick E. Mohs, a general surgeon from the University of Wisconsin, in the 1940s. Initially, a chemical fixative paste was applied to the skin to fix the tissue in situ; hence, the now outdated term Mohs chemosurgery. The fresh tissue technique, which omitted the chemical paste, was developed and refined in the 1970s. Mohs micrographic surgery is most useful for the treatment of higher risk NMSC. Mohs surgery is usually performed under local anesthesia in an outpatient Mohs surgical unit. After removal of all gross tumor, the surgeon excises a thin layer of tissue with 2- to 3-mm margins. The tissue is mapped, color-coded for orientation, and sent to the technician for frozen-section processing. The specimen is flexible and flattened, with the beveled peripheral skin edge placed in the same horizontal plane with the deep margin. In this plane, both the deep and peripheral margins are examined in one horizontal cut by frozen-section analysis with total (theoretically 100%) margin control. Good-quality frozen sections may be achieved only by a skilled and experienced Mohs histotechnician. The Mohs surgeon functions as both surgeon and pathologist. After histologic interpretation of the frozen-section specimens, the precise anatomic location of any residual tumor can be identified and re-excised until all margins are tumor free. The Mohs surgeon's ability microscopically to track subclinical tumor extensions results in the highest cure rate with maximal preservation of normal tissue. Soft tissue reconstruction can then be performed on the same day, after completion of Mohs surgical excision of the tumor. A multidisciplinary approach involving Mohs, plastic, head and neck, and oculo-plastic surgeons and radiation oncologists may be needed for extensive tumors. Mastering the Mohs technique is based on a steep learning curve. The American College of Mohs Micrographic Surgery and Cutaneous Oncology requires 1 to 2 years of fellowship training with a minimum of 500 to 600 cases before certification.