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.

Nevoid BCC syndrome (Gorlin's syndrome).

This rare disease is inherited as an autosomal dominant trait with high penetrance and variable expressivity. The gene is located on chromosome 9q22.3-q31. It has the following major features: multiple BCCs appear at birth or in early childhood; numerous small pits on the palms and soles (50% to 65%); epithelium-lined jaw cysts, which commonly cause symptoms (65% to 90%); ectopic calcification with lamellar calcification of falx cerebri (80%); and a variety of skeletal abnormalities, especially of the ribs, skull, and spine (70% to 75%). A characteristic facies is present in approximately 70% of patients . Numerous associated anomalies may be present. There is great variation in the number and behavior of the nevoid BCC. Although many patients have no BCCs or just a few, more than 250 BCCs can be present. Locally destructive tumors are not seen before puberty. Aggressive behavior can occur after puberty, and all patients must be followed closely. Most of the highly invasive tumors involve embryonic cleft areas of the face. Development of multiple BCCs is enhanced by exposure to light and x-ray irradiation, but they also occur on unexposed surfaces. Multiple bilateral jaw cysts are the presenting complaint in approximately 50% of patients; the syndrome was discovered by a dentist, R.J. Gorlin. The cysts appear during the first decade of life and displace the child's teeth, often in the premolar area. They cause pain, drainage, and jaw swelling. The occurrence of multiple skeletal anomalies is highly suggestive and may be the earliest clue to the diagnosis of nevoid BCC syndrome in children. Complete or partial bridging of the sella turcica is present in 75% of patients. Splayed and bifurcated ribs occur in 40% of patients.
The initial evaluation of patients suspected of having BCC syndrome should include the following: (1) detailed family history; (2) dental consultations; and (3) x-rays of jaws, skull, chest, spinal column, and hands.

NEVOID BASAL CELL CARCINOMA SYNDROME

SKIN
Multiple nevoid basal cell carcinomas

Pits--palms and soles (50% to 65%)

Milia, cysts (epithelial and sebaceous)


FACE AND MOUTH
Multiple jaw cysts (65% to 90%)

Presenting complaint in 50%

Characteristic facies (70%)

Mandibular prognathism

Broadening of the nasal root (25%)

Frontal/temporoparietal bossing

Ocular hypertelorism


CENTRAL NERVOUS SYSTEM
Lamellar calcification of falx cerebri (80%)

Bridging of the sella turcica (75%)

Mental retardation

Electroencephalographic abnormalities


SKELETAL SYSTEM ANOMALIES (70% TO 75%)
Rib anomalies (55%): bifurcation and splaying (40%), synostotic, or partial agenesis or rudimentary cervical ribs

Vertebrae (65%): kyphoscoliosis (50%), spina bifida occulta (40%)

Shortened metacarpals (usually 4th, 5th, or both) (28%)

Bone cysts--phalanges and other bones (46%)

Many others


OTHERS
Lymphomesenteric cysts

Ovarian fibromas or cysts

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

Basal Cell Carcnoma Higher Risk Factors

Non melanoma skin cancer ---> Basal cell carcinoma ---> metastatic risk

These include the following factors:
Recurrent tumor

Anatomic location
High risk: central face, eyelid, eyebrow, periorbital, nose, lip, chin, mandible, temple, ear, in front or behind the ear, genitalia, hand and foot
Medium risk: cheeks, forehead, scalp, and neck
Low risk: trunk, extremity (excluding hand/foot)

Size
Lesions +6 mm on high-risk area
Lesions +10 mm on medium-risk area
Lesions +20 mm on low-risk area

Histologic subtype pattern
Aggressive growth (morpheaform, fibrosing, sclerosing, infiltrating)
Micronodular

Ill-defined clinical borders
Perineural invasion
Development in sites of prior radiation
Immunosuppression