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  • Basal cell carcinomas (BCCs) are the most common cancers in humans. All BCCs have mutations activating the Hedgehog signaling pathway.

  • BCCs are caused by exposure to ultraviolet light and are associated with PTCH1 gene mutation in most cases.

  • BCCs are locally destructive and rarely metastatic.

  • BCCs are primarily treated by surgical excision, electrodesiccation and curettage, Mohs micrographic surgery, and topical agents.


Basal cell carcinoma (BCC) is the most common cancer in humans. It is estimated that more than 3 ­million new cases occur each year in the United States.1 The malignancy accounts for approximately 75% of all nonmelanoma skin cancers (NMSCs) and almost 25% of all cancers diagnosed in the United States.2 Epidemiological data indicate that the overall incidence is increasing worldwide significantly by 3% to 10% per year.3

BCC is more common in older individuals but is becoming increasingly frequent in people younger than 50 years of age. Christenson and coworkers noted a disproportionate increase in BCC in women younger than age 40 years.3 Men are affected slightly more often than are women. Tumors were more frequent in patients older than 60 years of age, and 57% were in men. The vast majority of BCCs were located on the head and neck.2

BCC tumors most typically develop on sun-exposed skin of lighter skinned individuals. Incidence rates of BCC in Asians living in Singapore increased from 1968 to 2006, especially among the older, fair-skinned Chinese patients.4 BCC is rare in dark skin because of the inherent photoprotection of melanin and melanosomal dispersion. An estimated 1.8% of BCCs occur in blacks, and BCC is approximately 19 times more common in whites than blacks.5

Risk factors for BCC have been well characterized and include ultraviolet radiation (UVR) exposure, light hair and eye color, northern European ancestry, and inability to tan.2


The pathogenesis of BCC involves exposure to UVR, particularly the ultraviolet (UV) B spectrum (290–320 nm) that induces mutations in tumor suppressor genes.6 UVB radiation damages DNA, leading to genetic alterations and neoplasms. UV-induced mutations in the p53 tumor suppressor gene have been found in about 50% of BCC cases.7,8

Malignant activation of the sonic hedgehog (SHH) signaling pathway, a developmental signaling pathway, is the pivotal abnormality in all BCCs.7 Common mutations that activate the aberrant HH signaling pathway are loss of PTCH1 or Suppressor of Fused (SUFU) and activation of Smoothened (SMO) (Fig. 111-1, discussed more in the basal cell nevus syndrome [BCNS] section of this chapter). Approximately 90% of sporadic BCCs have identifiable mutations in at least one allele of PTCH1, and an additional 10% have activating mutations in the downstream SMO protein.9 The most frequently identified mutations in ...

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