Answer: C

Basal cell carcinoma (BCC), the most commonly diagnosed skin cancer, arises from the basal epidermis of the skin.1 The absolute number of cases of BCC remains challenging to ascertain since nonmelanoma skin cancers are usually excluded from cancer registry statistics. However, the American Cancer Society estimated that in 2012, 5.4 million cases of nonmelanoma skin cancer were diagnosed in 3.3 million people, and of those cases, 80% were BCC.1 BCC is most often diagnosed in white adults and is less common in darker-skinned populations.2,3 The incidence of BCC increases with age and is 2-fold higher in older men than women.3

Sun exposure is the most important environmental risk factor for BCC.4 The timing, pattern, and intensity of ultraviolet (UV) radiation are all important modulators of risk. Recreational exposure to sunlight, especially in childhood or adolescence, and intense intermittent sun exposure are associated with a higher risk of BCC, while average annual cumulative sunlight exposure appears not to increase risk.4 Other risk factors for BCC include red or blond hair, fair complexion, and light eye color.1,4,5

Pharmacologic agents, such as psoralen with ultraviolet A (PUVA) therapy, significantly increase the risk of squamous cell carcinoma (SCC) but only moderately increase the risk of BCC.5,6 The use of photosensitizing medications such as tetracyclines increases vulnerability of the skin to UV radiation and thus has been implicated in risk of developing BCC.4 The use of tanning beds, particularly early in life, is associated with an increase in risk of all forms of nonmelanoma skin cancer.4,7 Exposure to ionizing radiation and arsenic, as well as immunosuppression, especially in the context of organ transplantation, are also linked to the development of BCC.5 Once a patient develops BCC, the risk of a subsequent BCC increases 10-fold.5

Activation of the hedgehog signaling pathway is present in both sporadic and genetic cases of BCC.8 Secreted sonic hedgehog protein inhibits the patched homolog 1 protein (PTCH1), halting its suppressive effects on intracellular signaling, such as its suppression of smoothened signaling.8 For example, loss of function of PTCH1 has been identified in sporadic BCC, while germline mutations in human patched 1 gene (PTCH1) are seen Gorlin syndrome.9,10 Additionally, mutations in tumor-suppressor gene TP53 are found in approximately 50% of sporadic BCC cases.8

BCC is generally seen on areas of the skin most exposed to sun, such as the head and neck (80%), trunk (15%), and arms and legs (5%).11 BCC is classified into 3 forms: nodular, superficial, and morpheaform.

  • Nodular BCC is the most common and presents as a pearly papule or nodule with arborizing telangiectasias and a rolled border, at times with central ulceration.8
  • Superficial BCC presents as a well-circumscribed, scaly, erythematous patch or plaque.12 The edge of these lesions may display a thin, rolled border with crusting or fine translucent small papules. Both nodular and superficial BCC can contain melanin, imparting brown, blue, or black color to these lesions.
  • Morpheaform BCC (also known as sclerosing, fibrosing, or infiltrative BCC) typically appears as an indurated, whitish, scar-like plaque with indistinct margins.8

On histopathologic examination, all subtypes of BCC display aggregations of basaloid keratinocytes, often with peripheral palisading, extending from epidermis to dermis. Histopathology can distinguish more indolent BCC subtypes (nodular and superficial) from more aggressive ones (morpheaform).8

The differential diagnosis for BCC ranges from benign conditions such as sebaceous hyperplasia, keratoacanthoma, inflammatory dermatoses, molluscum contagiosum, intradermal melanocytic nevus, and fibrous papule of the nose, to malignancies such as SCC, cutaneous B-cell lymphoma, melanoma, and Merkel cell carcinoma.13

The diagnosis of BCC can be made by an experienced clinician on visual inspection or by dermoscopy.8 Several characteristics can distinguish benign growths from BCC. Sebaceous hyperplasia, for example, can be differentiated from BCC by its yellowish coloration and central pore.14 Keratoacanthoma, unlike BCC, usually presents with a central keratin plug.15 Dermatitis or psoriasis generally respond to the application of topical steroids, while BCC will not.14

A pigmented BCC can be differentiated from malignant melanoma by the presence of a pearly, rolled border; however, any lesion with atypical characteristics such as melanin production must undergo biopsy. On histologic examination, melanoma will display large atypical melanocytes invading the epidermis and dermis.14

BCC can be pathologically distinguished from cutaneous B-cell lymphoma by the presence of basaloid aggregates that are connected to the epidermis, while B-cell lymphoma always spares the epidermis.14 Immunohistochemistry will reveal positivity for markers such as CD20, CD79a, CD10, or BCL6 in B-cell lymphoma, but not BCC.16

SCC also presents on sun-exposed sites of skin; however, in contrast with BCC, SCC is usually a flaky, red, sometimes pruritic plaque or nodule.14 On histologic examination, SCC often displays keratin pearls, while BCC does not.14

Prognosis is very good for BCC lesions as they rarely metastasize. Thus, the goal of treatment is to remove the lesion entirely and maximally preserve function and cosmesis.14 Lower-risk BCCs are often managed with electrodesiccation and curettage or surgical excision.17 Lower-risk BCCs less commonly can be treated with topical 5-fluorouracil or imiquimod, cryotherapy, or photodynamic therapy.17 Mohs surgery provides the highest cure rate and is the treatment of choice when a lesion is designated to be at high risk for recurrence and when anatomy and function need to be preserved.14 More recently, hedgehog pathway inhibitors, such as vismodegib, have been indicated in the treatment of locally advanced, multiple, or metastatic BCC.14

Because of the uncomplicated location and small size of the lesion in this case, the patient underwent excisional biopsy. Histopathology showed aggregates of basophilic, basaloid cells with peripheral palisading extending from the epidermis to the dermis, confirming a diagnosis of nodular BCC. The patient chose to undergo Mohs surgery to ensure clear surgical margins with little cosmetic disturbance.

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