Common Cutaneous Malignancies

1

How are skin cancers classified?

Primary cutaneous cancers are classified on the basis of their cell of origin within the skin ( Table 43.1 ). Skin cancers are most commonly derived from keratinocytes (e.g., squamous cell carcinoma [SCC], basal cell carcinoma [BCC]) or melanocytes (e.g., melanoma), which are normal components of the epidermis. Less commonly, they arise from other cells within the epidermis, dermis, or subcutis.

2

What are the most common nonmelanoma skin cancers (NMSCs)?

BCC and SCC make up the majority of NMSCs. In the United States, it is estimated that 5.4 million diagnoses of NMSC occur yearly in 3.3 million patients, which makes these the most prevalent of all malignancies. Common nonmelanoma skin premalignancies include actinic keratosis and actinic cheilitis.

Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol . 2015;151:1081–1086.

3

What is the most important cause of NMSC?

The overwhelming majority of precancerous and cancerous skin lesions are caused by sun exposure. Several observations and epidemiologic studies support the role of ultraviolet (UV) light in the production of skin cancers:

• 1.

  Most NMSCs develop on chronically sun exposed skin, with 80% or more occurring on the head and neck.

• 2.

  The incidence of NMSC is lower in more polar latitudes (e.g., Minneapolis) than equatorial latitudes (e.g., Hawaii).

• 3.

  Epidemiologic studies clearly demonstrate that NMSCs are much more common in individuals with lighter skin than in individuals with darker skin.

• 4.

  Individuals with genetic diseases that make them sensitive to UV radiation have higher rates of skin cancer.

• 5.

  In animal models, NMSC can be induced by solar irradiation and prevented by the use of sunscreens.

• 6.

  The risk of skin cancer is increased with use of tanning beds. It is estimated that nearly half a million cases of NMSC and ten thousand melanoma cases can be attributed to their use.

Kim RH, Armstrong AW. Nonmelanoma skin cancer. Dermatol Clin. 2012;30:125–139.

Rigel D. Cutaneous ultraviolet exposure and its relationship to the development of skin cancer. J Am Acad Dermatol. 2008;58:S129–S132.

Wehner MR, Chren NM, Nameth D, et al. International prevalence of indoor tanning: a systematic review and meta-analysis. JAMA Dermatol. 2014;150:390–400.

4

Are there any other causes of NMSC?

• Arsenic ingestion

• Chronic ulcers and scars (e.g., burn wounds)

• Environmental pollutants

• Familial syndromes (e.g., xeroderma pigmentosum, albinism, epidermodysplasia verruciformis)

• Local, prolonged heat exposure

• Topical exposure to tars and oils

• Viral infection (e.g., some strains of human papillomavirus)

• Radiation therapy

• Medications (voriconazole, BRAF-inhibitors, psoralen plus UVA therapy)

5

What special populations are at increased risk of NMSC?

• Organ transplant patients: NMSC is the most common malignancy in solid organ transplant recipients (OTRs). OTRs are at a 65 times higher risk of SCC and 10 times higher risk of BCC than the general population. The development of skin cancer in these patients appears to be linked to the duration and degree of immunosuppression required to prevent transplant rejection. The use of calcineurin inhibitors and azathioprine has been associated with increased risk of skin cancer in this population. In addition, individuals infected with human papillomavirus (HPV) have a higher risk. The ratio of SCCs to BCCs is 4:1 in OTRs, a reversal of the normal ratio seen in the general population. SCC in particular can behave more aggressively in this population; those who develop metastatic SCC have very poor outcomes.

• Human immunodeficiency virus (HIV) patients: NMSC is the most common non–acquired immune deficiency syndrome (AIDS)–defining cancer seen in HIV-positive patients. HIV-positive patients appear to maintain a normal ratio of BCCs to SCCs, but are twofold to sevenfold more likely to develop NMSC than the general population.

Wheless L, Jacks S, Mooneham Potter KA, et al. Skin cancer in organ transplant recipients: more than the immune system. J Am Acad Dermatol. 2014;71:359–365.

Chockalingam R, Downing C, Tyring SK. Cutaneous squamous cell carcinomas in organ transplant recipients. J Clin Med . 2015;4(6):1229–1239.

Zhao H, Shu G, Wang S. The risk of non-melanoma skin cancer in HIV-infected patients: new data and meta-analysis. Int J STD AIDS . 2016;27(7):568–575.

Honda K. HIV and skin cancer. Dermatol Clin. 2006;24:521–530.

6

How are NMSCs diagnosed?

A cutaneous malignancy should be considered in any patient who reports a new skin lesion, particularly in sun-exposed regions. The gold standard of diagnosis is shave, punch, or excisional biopsy, with the choice of biopsy technique depending on the size and location of the suspected malignancy. Current research is focused on developing noninvasive methods of diagnosing NMSC by using techniques such as specialized ultrasonography and microscopy. These methods, however, are currently in development and have not replaced skin biopsy with histologic examination as the gold standard for diagnosis.

Mogensen M, Jemec G. Diagnosis of nonmelanoma skin cancer/keratinocyte carcinoma: a review of the diagnostic accuracy of nonmelanoma skin cancer diagnostic tests and technologies. Dermatol Surg. 2007;33:1158–1174.

7