Basal Cell Carcinoma

Basal cell carcinoma arises primarily from an interplay between environmental and genetic factors. Basal cell carcinomas are also associated with genetic syndromes and may arise in a nevus sebaceus. Xeroderma pigmentosum represents an inherited defect in DNA repair that can result in nonmelanoma skin cancer and in melanoma. Basal cell nevus syndrome (Gorlin syndrome) is an autosomal dominant disorder that results in multiple basal cell carcinomas as well as in medulloblastomas, meningiomas, breast cancers, non-Hodgkin lymphomas, and ovarian cancers. Bazex-Dupré-Christol syndrome is a rare X-linked genodermatosis characterized by a triad of early onset of multiple basal cell carcinomas, follicular atrophoderma, and hypotrichosis.

Most basal cell carcinomas are caused by aberrant activation of the Hedgehog signaling (most commonly due to loss-of-function mutations in the PTCH1 gene). The most significant environmental risk factor is UV (both UVA and UVB) radiation, in particular, intermittent and intense sun exposure during childhood and adolescence. Less frequently implicated environmental factors include exposure to arsenic and profound immunosuppression (especially organ transplantation).

The clinical manifestations of basal cell carcinomas are highly variable.

Most commonly, the carcinoma begins as a shiny papule, enlarges slowly, and, after a few months or years, shows a shiny, pearly border with prominent engorged vessels (telangiectases) on the surface and a central dell (ie, central depression) or ulcer. The carcinomas often alternately crust and heal, which may unjustifiably decrease patient and physician concerns about the seriousness of the lesion. Recurrent itching, crusting, or bleeding is not unusual. Most lesions are painless and nontender to palpation. Chronic nonhealing lesions, particularly in sun-exposed skin, should prompt consideration of basal cell carcinoma.

Basal-cell carcinoma lesions typically occur in sun-exposed areas (1). Lesions occur most commonly on the head and neck (80% of cases), followed by the trunk (15%), and less commonly on the arms and legs. The palms and soles are typically spared, and involvement of the axillary, mammary, or genital regions is rare.

There are several types of basal cell carcinomas. The most common types are (2):

• Nodular (approximately 51% of basal cell carcinomas): These types are small, shiny, firm, almost translucent to pink nodules with telangiectases, usually on the face or other sun-exposed areas. Ulceration and crusting are common.

• Superficial (approximately 34%): These types are red or pink, marginated, thin papules or plaques, commonly on the trunk, that can be mistaken for psoriasis or other localized dermatitis.

• Morpheaform and infiltrative (5 to 10%): These types are flat, scarlike, indurated plaques that can be flesh-colored or light red and have vague borders. They are considered high-risk because of their tendency for deeper invasion and higher recurrence risk.

• Mixed: This type includes histopathologic features of more than one subtype.

• Other: Other types are possible (eg, micronodular, basosquamous). Nodular and superficial basal cell carcinomas can produce pigment (sometimes called pigmented basal cell carcinomas).

Manifestations of Basal Cell Carcinoma

Nodular Basal Cell Carcinoma (1)

This photo shows a superficial, slowly growing, ulcerated nodule.

This photo shows a superficial, slowly growing, ulcerated nodule.

Photo provided by Thomas Habif, MD.

Nodular Basal Cell Carcinoma (2)

This lesion usually appears as a firm, pearly, dome-shaped nodule often displaying multiple telangiectatic vessels coursing over its borders.

This lesion usually appears as a firm, pearly, dome-shaped nodule often displaying multiple telangiectatic vessels cour

... read more

© Springer Science+Business Media

Superficial Basal Cell Carcinoma

This photo shows a superficial basal cell carcinoma on the forehead of a patient. This lesion involves only the epidermis.

This photo shows a superficial basal cell carcinoma on the forehead of a patient. This lesion involves only the epiderm

... read more

RICHARD USATINE MD / SCIENCE PHOTO LIBRARY

Morpheaform Basal Cell Carcinoma

This basal cell carcinoma appears as a flat, waxy, poorly demarcated plaque with prominent telangiectasia.

This basal cell carcinoma appears as a flat, waxy, poorly demarcated plaque with prominent telangiectasia.

© Springer Science+Business Media

Pigmented Basal Cell Carcinoma (1)

Pigmented basal cell carcinoma is a less common variant. These lesions are sometimes misdiagnosed as pigmented nevi or malignant melanomas.

Pigmented basal cell carcinoma is a less common variant. These lesions are sometimes misdiagnosed as pigmented nevi or

... read more

© Springer Science+Business Media

Pigmented Basal Cell Carcinoma (2)

This photo shows an advanced pigmented basal cell carcinoma with ulceration on the cheek of a patient.

This photo shows an advanced pigmented basal cell carcinoma with ulceration on the cheek of a patient.

BSIP, GIRAND / SCIENCE PHOTO LIBRARY

Nodular Basal Cell Carcinoma (1)

This photo shows a superficial, slowly growing, ulcerated nodule.

This photo shows a superficial, slowly growing, ulcerated nodule.

Photo provided by Thomas Habif, MD.

Nodular Basal Cell Carcinoma (2)

This lesion usually appears as a firm, pearly, dome-shaped nodule often displaying multiple telangiectatic vessels coursing over its borders.

This lesion usually appears as a firm, pearly, dome-shaped nodule often displaying multiple telangiectatic vessels cour

... read more

© Springer Science+Business Media

Superficial Basal Cell Carcinoma

This photo shows a superficial basal cell carcinoma on the forehead of a patient. This lesion involves only the epidermis.

This photo shows a superficial basal cell carcinoma on the forehead of a patient. This lesion involves only the epiderm

... read more

RICHARD USATINE MD / SCIENCE PHOTO LIBRARY

Morpheaform Basal Cell Carcinoma

This basal cell carcinoma appears as a flat, waxy, poorly demarcated plaque with prominent telangiectasia.

This basal cell carcinoma appears as a flat, waxy, poorly demarcated plaque with prominent telangiectasia.

© Springer Science+Business Media

Pigmented Basal Cell Carcinoma (1)

Pigmented basal cell carcinoma is a less common variant. These lesions are sometimes misdiagnosed as pigmented nevi or malignant melanomas.

Pigmented basal cell carcinoma is a less common variant. These lesions are sometimes misdiagnosed as pigmented nevi or

... read more

© Springer Science+Business Media

Pigmented Basal Cell Carcinoma (2)

This photo shows an advanced pigmented basal cell carcinoma with ulceration on the cheek of a patient.

This photo shows an advanced pigmented basal cell carcinoma with ulceration on the cheek of a patient.

BSIP, GIRAND / SCIENCE PHOTO LIBRARY

• Biopsy and histopathological examination

The diagnosis of basal cell carcinoma consists of clinical evaluation of a suspicious skin lesion followed by confirmation with biopsy and histologic examination. Histopathological examination confirms the subtype of basal cell carcinoma, which is important for guiding treatment.

• Usually with local therapies

Treatment of basal cell carcinoma should be performed by a specialist.

The clinical appearance, size, site, and histologic subtype determine choice of treatment. Treatment selection depends on risk stratification (1).

Low-risk tumors are managed with:

• Primarily surgical excision, curettage, or electrodesiccation

• Nonsurgical modalities (eg, topical chemotherapy [imiquimod or 5-fluorouracil], cryotherapy, photodynamic therapy)Nonsurgical modalities (eg, topical chemotherapy [imiquimod or 5-fluorouracil], cryotherapy, photodynamic therapy)

• Occasionally radiation therapy

Low-risk features include:

• Location on the trunk or extremities with a diameter < 2 cm

• Well-defined clinical borders

• Primary (not recurrent) tumors

• Nodular or superficial subtypes

• Absence of perineural involvement

Recurrence rates are generally higher when nonsurgical approaches are used (with the exception of radiation therapy) (2), but cosmetic outcomes may be superior (3).

High-risk tumors usually require one of the following:

• Mohs micrographic surgery

• Surgical excision with peripheral and deep en face margin assessment techniques, for which tissue borders are progressively excised until specimens are tumor-free,as determined by microscopic examination during surgery

High-risk features include:

• Tumors of any size on the head, neck, hands, feet, pretibial, or anogenital areas

• Diameter ≥ 2 cm on trunk and extremities

• Poorly-defined borders

• Recurrent tumors

• Aggressive growth patterns (basosquamous, infiltrative, morpheaform)

• Perineural involvement

• Immunosuppression

• Prior radiation therapy site

If patients have metastatic or locally advanced disease and are not candidates for surgery or radiation therapy (eg, because lesions are large, recurrent, or metastatic), vismodegib or sonidegib may be given (If patients have metastatic or locally advanced disease and are not candidates for surgery or radiation therapy (eg, because lesions are large, recurrent, or metastatic), vismodegib or sonidegib may be given (4, 5). Both medications inhibit the Hedgehog pathway. Cemiplimab, a programmed death-receptor 1 (PD-1) inhibitor, is an option for patients who cannot tolerate Hedgehog pathway inhibitors (). Both medications inhibit the Hedgehog pathway. Cemiplimab, a programmed death-receptor 1 (PD-1) inhibitor, is an option for patients who cannot tolerate Hedgehog pathway inhibitors (6).

Basal cell carcinoma generally has an excellent prognosis because of the extremely low metastatic potential and high cure rates following appropriate treatment (1). While basal cell carcinomas rarely metastasize, they may invade healthy tissues (ie, local spread). Rarely, patients die because the carcinoma invades or impinges on underlying vital structures or orifices (eg, eyes, ears, mouth, bone, dura mater).

Approximately 40% of patients with a history of keratinocyte cancer will develop another keratinocyte cancer within 5 years of the original carcinoma (2). Risks of recurrence are progressively higher for each recurrence (ie, for third compared to second, and fourth compared to third). Consequently, long-term surveillance is recommended; patients with a history of basal cell carcinoma should be seen annually for a skin examination.

Because basal cell carcinoma is associated with ultraviolet (UV) radiation exposure, a number of measures (eg, sun avoidance measures, use of protective clothing, use of sunscreen) are recommended to limit exposure. For more detailed information, see Prevention of Effects of Sun Exposure.