It is estimated that more than 1 million basal cell carcinomas are treated in the United States annually. By far the most important risk factor is cumulative sun exposure; basal cell carcinoma is more common in warm southern regions of the United States, and its incidence is 40-fold higher in sunny climates near the equator, such as Australia, than it is in Northern European locales. Individual tumors usually are cured by local excision, but approximately 40% of patients develop another basal cell carcinoma within 5 years. Advanced lesions may ulcerate, and extensive local invasion of bone or facial sinuses may occur if the lesions are neglected. Metastasis is exceedingly rare. Hedgehog pathway inhibitors are used to treat locally advanced or metastatic tumors.
Fig. 24.17 Basalcellcarcinoma.(A)Aprototypicalpearly,smooth-surfacedpapulewithtelangiectaticvessels.(B)Tumoriscomposedofnestsofbasaloidcellsinfiltratingafibroticstroma.(C)Tumorcellswithscantcytoplasmandsmallhyperchromaticnucleithatpalisadeontheoutsideofthenest.Thecleftbetweenthetumorcellsandthestromaisahighlycharacteristicartifactofsectioning.
The incidence of both basal cell and squamous cell carcinomais strongly correlated with increasing lifetime sun exposure.
Risk factors for cutaneous squamous cell carcinoma includefair skin, UV light exposure, exposure to carcinogenic chemicals, chronic skin inflammation and scarring, and HPV infection(in the setting of immunosuppression).
Cutaneous squamous cell carcinoma has the potential for metastasis but usually is recognized and excised before it does so.
Basal cell carcinoma, the most common malignancy worldwide, is a locally aggressive tumor associated with mutations in theHedgehog pathway. Metastasis is very rare.
Strictly speaking, the term nevus denotes any congenital lesion of the skin. Melanocytic nevus, however, refers to any benign congenital or acquired neoplasm of melanocytes.
Melanocytic nevi are benign neoplasms caused by somatic gain-of-function mutations in BRAF or RAS. Nevi are derived from melanocytes, pigment-producing cells with dendritic projections that are normally interspersed among basal keratinocytes. You will recall that BRAF encodes a serine/threonine kinase that lies downstream of RAS in the extracellular regulated kinase (ERK) pathway. Experimental evidence suggests that unbridled BRAF/RAS signaling initially induces melanocytic proliferation followed by senescence. How these opposing effects are coordinated is unclear, but it is believed that the “brake” on proliferation provided by induced senescence explains why very few nevi transform into malignant melanomas. Indeed, the growth and migration of nevus cells from the dermoepidermal junction into the underlying dermis is accompanied by morphologic changes that are taken as evidence of cellular senescence (
Fig. 24.18 ). Superficial nevus cells are larger and tend to produce melanin pigment and grow in nests; deeper nevus cells are smaller, produce little or no pigment, and grow in cords or single cells. The deepest nevus cells have fusiform contours and grow in fascicles. This sequence of morphologic changes is of diagnostic importance, since they are absent from  melanomas.