Skin Cancer Types
The diversity of cell types in the epidermal and dermal skin layers lends the possibility of several different types of skin cancers upon malignant transformation of these cells. In practice, the vast majority of skin cancers in humans are one of three types: melanoma (a malignancy of melanocytes); or one of two non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma, both malignancies of keratinocytes) (Thieu 2013; Lin 2011). Each has unique features and metastatic potential.
Melanoma results from the malignancy of pigmented melanocytes that reside deep in the epidermis; this occurs by mutation in one of several regulatory genes (eg, genes involved in regulating the cell cycle or that control cell division), ultimately allowing uncontrolled melanocyte growth and invasion of surrounding tissues. These defects may be hereditary or acquired (Erb 2008; Dunki-Jacobs 2013). UV exposure also has a role in this process (Rass 2008). Additionally, local immunosuppression caused by malignant melanocytes is thought to enable melanoma to escape host immune defenses (Erb 2008). Melanoma rapidly metastasizes, making it the most dangerous of the skin cancers (Uzarska 2013; Dunki-Jacobs 2013). While the median age at diagnosis is 61, melanoma occurs over a wide distribution of ages and is one of the most frequent cancers found in adolescents and young adults (Dunki-Jacobs 2013).
Non-Melanoma Skin Cancers
Basal cell carcinoma. Basal cell carcinomas, which represent 80% of non-melanoma skin cancers, are the most commonly diagnosed cancer in the United States (Thieu 2013). They arise from pluripotent keratinocytes (stem cells) located in the basal layer of the epidermis and around hair follicles (Erb 2008; Firnhaber 2012; Ponten 1994). UV radiation appears to be the principal catalyst in the malignant transformation of basal cells (Thieu 2013), and exposure to sunlight in childhood and adolescence may be an important determinant of malignancy (Firnhaber 2012). Up to 20% of these cancers occur in people under age 50. They are locally aggressive, but rarely metastasize to distant organs (Robinson 2003; Kurian 2013). In addition to the disruption in cellular defenses (p53 gene mutation), a basal cell malignancy may also be caused by mutations in genes that regulate the growth and maintenance of keratinocyte stem cells (Erb 2008).
Squamous cell carcinoma. Squamous cell carcinomas represent about 20% of non-melanoma skin cancer cases (Alam 2001). They are thought to originate from keratinocytes (like basal cell carcinomas), but from a more superficial layer of the epidermis, not the basal layer (Erb 2008). Also in contrast to basal cell carcinomas, there is a higher risk of metastasis (Alam 2001; Jennings 2010). Squamous cell carcinomas are strongly associated with UV radiation exposure as well as other phenotypic markers (fair skin, light eyes, light-colored hair; see section titled “Causes and Risk Factors”). Their association with cumulative sunlight exposure makes them an uncommon skin cancer in people younger than 50 years old (Firnhaber 2012). Squamous cell carcinomas may also be induced through exposure to chemical carcinogens (Thieu 2013).
Other non-melanoma skin cancers are rare, making up <1% of all skin cancers (ACS 2014a). These include (Thieu 2013; Rehal 2013; Lazareth 2013; Sebastien 1993; Lober 1994):
- Merkel cell carcinoma – a rare, very aggressive malignancy of the sensory Merkel cells with high rates of local recurrence and distant metastasis;
- Sebaceous carcinoma – malignancy of sebaceous gland cells;
- Eccrine porocarcinoma – malignancy of sweat gland cells;
- Atypical fibroxanthoma – a dermal tumor with low-moderate metastatic potential; and
- Microcystic adnexal carcinoma – a locally invasive tumor derived from sweat gland cells.