Skin Cancer

1

What are the common cutaneous malignancies?

Cutaneous malignancies are classified into melanoma and nonmelanoma skin cancers. Nonmelanoma skin cancers include basal cell carcinoma and squamous cell carcinoma, which account for the majority of all skin cancers. Melanoma skin cancers account for only 5% of cutaneous malignancies but result in 90% of the mortality from skin cancer in patients less than 50 years old. Rare nonmelanoma skin cancers include Merkel cell carcinoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, and cutaneous T-cell lymphoma. Overall, there are more skin cancers in the United States than all other malignancies combined, and it is estimated that 20% of the population of the United States will develop a skin cancer during their lifetime.

2

What is a basal cell carcinoma?

Basal cell carcinoma (BCC) is a cutaneous neoplasm that arises from the basal layer of the epidermis. It is the most common cancer in humans and the most common type of skin cancer. BCC is more commonly found in men, although in the last decade the incidence has been increasing in women. It is most diagnosed in middle-aged individuals with a median age of diagnosis of 68 years. BCC accounts for up to 75% of all nonmelanoma skin cancers.

BCC is classified according to histologic appearance, including superficial , nodular , micronodular , desmoplastic , pigmented , and basosquamous BCCs. The classic appearance of a BCC is a skin-colored to pink pearly papule or plaque with a rolled border and possibly central ulceration ( Fig. 12.1A and 12.1B ). Superficial BCCs present as thin, pink, scaly papules or plaques and are most common on the trunk in younger patients ( Fig. 12.1C ). Desmoplastic BCCs, also known as morpheaform, infiltrating, or sclerosing BCCs, may have a more subtle clinical appearance, presenting as flat, slightly atrophic lesions, similar to a scar ( Fig. 12.1D ). Desmoplastic and basosquamous BCCs have a more aggressive clinical course and a higher risk of recurrence than other histologic subtypes of BCC. Risk factors for BCC include intermittent rather than cumulative ultraviolet (UV) exposure, fair skin, immunosuppression, indoor tanning, ionizing radiation, exposure to chemicals such as arsenic, coal tar psoralen plus ultraviolet A (UVA) radiation, and rare genetic syndromes, such as basal cell nevus syndrome (Gorlin’s syndrome). Although BCCs can be locally aggressive, they almost never metastasize (rate 1/35,000).

3

What is squamous cell carcinoma?

Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy and arises from the keratinocytes within the epidermis. SCC represents approximately 20% of all skin cancers and can have a more aggressive clinical course than BCC. SCC in situ, also known as Bowen’s disease, is confined to the epidermis of the skin and presents as a thin, pink, scaly papule or plaque ( Fig. 12.2A ). Invasive SCC presents as a pink, crusted papule or nodule on sun-damaged skin ( Fig. 12.2B ). Common locations for SCC are sun-exposed areas such as the face, forearms, and dorsal hands. SCCs associated with human papillomavirus (HPV) can occur on the hands, feet, and genitals. SCCs can also occur in areas of chronic inflammation such as a stasis ulcer or burn site (Marjolin’s ulcer).

Risk factors for SCC include fair skin, UV exposure, male sex, immunosuppression such as in human immunodeficiency virus (HIV) and solid organ transplant, cigarette smoking, HPV infection, indoor tanning, ionizing radiation, exposure to chemicals such as arsenic, coal tar psoralen plus UVA, mineral oil, soot and mechlorethamine, certain medications, chronic nonhealing ulcers and scars, chronic inflammatory skin conditions, and rare genetic syndromes. The risk of metastatic SCC is less than 5% in sun-exposed skin but can be significantly higher for tumors with known risk factors. Metastases from SCC are most often found in regional lymph nodes but can also be distant. The role of sentinel lymph node biopsy (SLNB) in the evaluation and management of high-risk SCC is debated.

4

What makes an SCC high risk?

Although most SCCs can be successfully treated surgically, there is a subset that are associated with higher rates of recurrence, metastasis, and death. It is estimated that approximately 3000 to 9000 Americans die each year from SCC, a rate comparable to deaths from melanoma. SCCs are considered high risk based on several factors, including location, etiology, histologic features, and host immune status. High-risk factors include the following:

• Diameter: A tumor diameter of >2 centimeters, especially those >4 centimeters in their greatest dimension.

• Depth: Tumors that are >2 millimeters deep but especially those >6 millimeters in thickness, extension beyond the subcutaneous fat, and bony invasion.

• Perineural involvement: Perineural involvement of nerves >0.1 millimeter in diameter (large caliber) or clinical/radiographic evidence of named nerve involvement or tumor cells within the nerve sheath of a nerve lying deeper than the dermis.

• Histology: Poorly differentiated tumor on hisbottomathology

• Previously treated/recurrent SCC

• Anatomic site: Ear, lip, genitals

• SCC arising in a scar or a site of chronic inflammation

• Host immune status : immunosuppression, chronic lymphocytic leukemia, genetic DNA repair defects such as xeroderma pigmentosum

5

How is SCC staged?

Several staging systems exist for cutaneous SCC. The American Joint Committee on Cancer (AJCC) staging system was most recently revised in October 2016 (eighth edition) to better stratify high-risk SCC ( Table 12.7 ). An alternative staging system, the Brigham and Women’s Hospital (BWH) staging system, was proposed in 2013 in order to identify which T2 tumors were higher risk. Patients with high-risk SCCs based on staging may need imaging, adjuvant treatment such as radiation, and closer clinical follow-up.

6

What are the most common cutaneous malignancies in the transplant population?

Transplant recipients are more likely to develop numerous aggressive nonmelanoma skin cancers and should be counseled on the importance of sun-protective measures, regular skin exams, and skin self-checks. SCC is by far the most common cutaneous malignancy in transplant recipients. Transplant recipients are 65 to 250 times more likely to develop SCCs than the general population and 6 to 16 times more likely to develop BCCs. The reported risk of developing an invasive melanoma is two fold higher in the transplant population than in the general population in White people and 17 times greater in Black people. Kaposi’s sarcoma and Merkel cell carcinoma are also seen more commonly in transplant recipients. Rates of skin cancer development and skin cancer mortality increase with the length of immunosuppression and level of immunosuppression and in patients with a baseline high risk for skin cancer. Mortality from skin cancer may approach 27% in cardiac transplant recipients.

7

What is Merkel cell carcinoma?

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neoplasm that is more common in older immunosuppressed patients. It presents as a rapidly enlarging pink or violaceous nodule on the head and neck or other sun-exposed areas. MCC was suspected to have a neuroendocrine origin for many years; however, in 2008, it was discovered that a polyomavirus was present in the majority of MCCs and the tumor is now considered to be infectious in origin, similar to HPV-induced malignancies. Other risk factors that contribute to the etiology of MCC include UV radiation exposure and immunosuppression (24-fold higher risk). MCCs grow rapidly, and up to 30% are metastatic at presentation. Treatment consists of surgical excision, often with SLNB and lymph node dissection if necessary, followed by adjuvant radiation therapy to the surgical site and nodal basin. Even with therapy, outcomes are poor, with 5-year mortality at 30%.

8

What is a keratoacanthoma and how is it treated?

Keratoacanthoma (KA) is a type of SCC that presents as an enlarging skin-colored or red nodule, often with a central crater that may be filled with keratinous debris ( Fig. 12.3 ). KAs usually develop over a few weeks and then are often reported to spontaneously resolve over months, leaving a scar. KAs are generally solitary but can be multiple in certain genetic syndromes. Given the difficulty in distinguishing a KA from a well-differentiated SCC, both clinically and histologically, these tumors are best considered a variant of well-differentiated SCC and treated as such.

9

What is an actinic keratosis and how is it treated?

An actinic keratosis (AK) is a precancerous lesion that presents as a skin-colored to pink rough papule on sun-exposed skin ( Fig. 12.4 ). Often, AKs are more easily felt than seen and patients describe them as areas that develop a crust that later falls off and reforms. If left untreated, AKs can develop into invasive SCC. Although the rate of transformation is thought to be roughly 1/100 per year, up to 60% of SCCs arise from an AK. As a result, it is recommended that AKs be treated in most cases rather than observed. AKs can be treated with destructive mechanisms such as curettage, cryotherapy, dermabrasion, or photodynamic therapy; bottomical medications such as fluorouracil, imiquimod, ingenol mebutate, and diclofenac; and field-ablative techniques such as chemical peels and laser resurfacing. Isolated lesions are most often treated with destructive methods such as cryotherapy. Field-directed therapy is generally recommended for patients with a larger number of AKs. AKs are not treated surgically, because they are non malignant, ill-defined, and often diffusely present across sun-damaged skin. The risk factors for AKs are similar to those for SCC.

10

What is actinic cheilitis?

Actinic cheilitis describes the precancerous sun damage changes that typically occur on the lower lip of older adults. It is the mucosal equivalent of an AK but has a higher risk of transformation to SCC. Actinic cheilitis can be treated similar to AKs with cryotherapy, bottomical agents, or photodynamic therapy.

11

What is Mohs micrographic surgery?

Mohs micrographic surgery (MMS) is a technique for treating skin cancer developed by Dr. Frederic Mohs in 1938. The modern technique of MMS is a single-day procedure performed under local anesthesia designed to provide high cure rates and conserve normal, uninvolved skin. During MMS, a skin cancer is removed in a specific beveled disc shape and the resected tissue is mapped out with ink to provide accurate orientation. This tissue is then processed into frozen sections and stained, using a method of horizontal en face sections that allows for visualization of 100% of the peripheral and deep margins (standard tissue processing examines <1% of the surgical margin). The tissue is examined under the microscope by the Mohs surgeon and the areas of tumor are precisely mapped out. If needed, the patient then has additional tissue removed only in the areas that were positive for tumor. Each excision and visualization of tissue is referred to as a Mohs stage. As many stages as necessary are taken to ensure that the entire tumor is completely removed ( Fig. 12.5 ), at which time surgical reconstruction may be performed. Because all margins are examined during MMS, it offers high cure rates while promoting tissue conservation.