Basal-cell carcinoma

Basal-cell carcinoma, also known as basal-cell cancer, basalioma, or rodent ulcer, is the most common type of skin cancer. It often appears as a painless, raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raised area with ulceration. Basal-cell cancer grows slowly and can damage the tissue around it, but it is unlikely to spread to distant areas or result in death.
Risk factors include exposure to ultraviolet light, having lighter skin, radiation therapy, long-term exposure to arsenic, and poor immune-system function. Exposure to UV light during childhood is particularly harmful. Tanning beds have become another common source of ultraviolet radiation. Diagnosis often depends on skin examination, confirmed by tissue biopsy.
Whether sunscreen affects the risk of basal-cell cancer remains unclear. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small; otherwise, Mohs surgery is generally recommended. Other options include electrodesiccation and curettage, cryosurgery, topical chemotherapy, photodynamic therapy, laser surgery, or the use of imiquimod, a topical immune-activating medication. In the rare cases in which distant spread has occurred, chemotherapy or targeted therapy may be used.
Basal-cell cancer accounts for at least 32% of all cancers globally. Of skin cancers other than melanoma, about 80% are BCCs. In the United States, about 35% of White males and 25% of White females are affected by BCC at some point in their lives.
Basal-cell carcinoma is named after the basal cells that form the lowest layer of the epidermis. It is thought to develop from the folliculo–sebaceous–apocrine germinative cells called trichoblasts.

Signs and symptoms

Individuals with basal-cell cancer typically present with a shiny, pearly skin nodule, but superficial BCC can present as a red patch similar to eczema. Infiltrative or morpheaform BCCs can present as a skin thickening or scar tissue – making diagnosis difficult without using tactile sensation and a skin biopsy. Visually distinguishing BCC from acne scar, actinic elastosis, and recent cryodestruction inflammation is often difficult.

Cause

Most BCCs occur on sun-exposed areas of the body.

Pathophysiology

Basal-cell carcinoma is named after the basal cells that populate the lowest layer of the epidermis due to the histological appearance of the cancer cells under the microscope. Nevertheless, not all BCCs originate within the basal layer. Some are thought to develop from the folliculo–sebaceous–apocrine germinative cells known as trichoblasts. Trichoblastic carcinoma is a term used to describe a rare and potentially aggressive malignancy that is also thought to arise from trichoblasts and may resemble a benign trichoblastoma. It has been suggested that lesions diagnosed as trichoblastic carcinoma may actually themselves be BCC.
Overexposure to the sun leads to the formation of thymine dimers, a form of DNA damage. While DNA repair removes most UV-induced damage, not all crosslinks are excised, so cumulative DNA damage can lead to mutations. Apart from the mutagenesis, overexposure to sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells. Studies of the role of DNA repair in susceptibility to sunlight-induced BCC indicated that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.
Basal-cell carcinomas can often occur in association with other lesions of the skin, such as actinic keratosis, seborrheic keratosis, and squamous-cell carcinoma. In a small proportion of cases, BCC also develops as a result of basal-cell nevus syndrome, or Gorlin syndrome, which is also characterized by keratocystic odontogenic tumors of the jaw, palmar or plantar pits, calcification of the falx cerebri, and rib abnormalities. The cause of this syndrome is a mutation in the PTCH1 tumor suppressor gene located in chromosome 9q22.3, which inhibits the hedgehog signaling pathway. A mutation in the SMO gene, which is also on the hedgehog pathway, also causes BCC.

Diagnosis

To diagnose basal-cell carcinomas, a skin biopsy is performed for histopathologic analysis. The most common method is a shave biopsy under local anesthesia. Most nodular BCCs can be diagnosed clinically; however, other variants can be challenging to distinguish from benign lesions such as intradermal naevus, sebaceomas, fibrous papules, early acne scars, and hypertrophic scarring. Exfoliative cytology methods have high sensitivity and specificity for confirming the diagnosis of BCC when clinical suspicion is high, but of unclear usefulness otherwise.

Characteristics

Basal-cell carcinoma cells resemble epidermal basal cells and are usually well differentiated.
In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only BCC cells.

Main classes

Basal-cell carcinoma can broadly be divided into three groups, based on the growth patterns.

Superficial basal-cell carcinoma, formerly referred to as in-situ basal-cell carcinoma, is characterized by a superficial proliferation of neoplastic basal-cells. This tumor is generally responsive to topical chemotherapy, such as imiquimod, or fluorouracil, although surgical treatment is better able to ensure complete removal and confirm that there is not an underlying more aggressive subtype that was not sampled in the initial biopsy.
Infiltrative basal-cell carcinoma, which also encompasses morpheaform and micronodular basal-cell cancer, is more difficult to treat with conservative methods, given its tendency to penetrate into deeper layers of the skin.
Nodular basal-cell carcinoma includes most of the remaining categories of basal-cell cancer. It is not unusual to encounter heterogeneous morphologic features within the same tumor.
Nodular basal-cell carcinoma

Nodular basal-cell carcinoma accounts for 50% of all BCC. It most commonly occurs on the sun-exposed areas of the head and neck. Histopathology shows aggregates of basaloid cells with well-defined borders, showing a peripheral palisading of cells and one or more typical clefts. Such clefts are caused by shrinkage of mucin during tissue fixation and staining. Central necrosis with eosinophilic, granular features may also be present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may also be present, especially in long-standing lesions. Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions. Adenoidal BCC can be classified as a variant of NBCC, characterized by basaloid cells with a reticulated configuration extending into the dermis.

Other subtypes

Other more specific subtypes of basal-cell carcinoma include:

Type	Histopathology	Other characteristics	Image
Cystic basal-cell carcinoma		Morphologically characterized by dome-shaped, blue-gray cystic nodules.
Morpheaform basal-cell carcinoma	Narrow strands and nests of basaloid cells, surrounded by dense sclerotic stroma.	Aggressive
Infiltrative basal-cell carcinoma	Deep infiltration.	Aggressive	-
Micronodular basal-cell carcinoma	Small and closely spaced nests.
Superficial basal-cell carcinoma		Occurs most commonly on the trunk and appears as an erythematous patch.
Pigmented basal-cell carcinoma exhibits increased melanization.		About 80% of all basal-cell carcinoma in Chinese are pigmented while this subtype is uncommon in white people.	-
Jacob's ulcer	Nodular, with central necrosis.	Generally a large skin lesion with central necrosis.	-
Fibroepithelioma of Pinkus	Anastomosing epithelial strands in a fenestrated pattern	Most commonly occurs on the lower back.
Polypoid basal-cell carcinoma	Exophytic nodules	Generally on head and neck.	-
Pore-like basal-cell carcinoma		Resembles an enlarged pore or stellate pit.	-
Aberrant basal-cell carcinoma		Absence of any apparent carcinogenic factor, and occurring in odd sites such as the scrotum, vulva, perineum, nipple, and axilla.	-

Aggressiveness patterns

There are mainly three patterns of aggressiveness, based mainly on the cohesion of cancer cells:

Low-level aggressive pattern	Moderately aggressive pattern	Highly aggressive pattern

Differential diagnoses

Radicality

In suspected but uncertain BCC cells close to the resection margins, immunohistochemistry with BerEp4 can highlight the BCC cells.

Prevention

Basal-cell carcinoma is a common skin cancer and occurs mainly in fair-skinned patients with a family history of this cancer. Sunlight is a factor in about two-thirds of these cancers; therefore, doctors recommend sunscreens with at least SPF 30. However, a Cochrane review examining the effect of solar protection in preventing the development of basal-cell carcinoma or cutaneous squamous cell carcinoma found that there was insufficient evidence to demonstrate whether sunscreen was effective for the prevention of either of these keratinocyte-derived cancers. The review did ultimately state that the certainty of these results was low, so future evidence could very well alter this conclusion. One-third occur in non-sun-exposed areas; thus, the pathogenesis is more complex than UV exposure as the cause.
The use of a chemotherapeutic agent such as 5-Fluorouracil or imiquimod can prevent the development of skin cancer. It is usually recommended to individuals with extensive sun damage, a history of multiple skin cancers, or rudimentary forms of cancer. It is often repeated every 2 to 3 years to decrease the risk of skin cancer further.