Porth's Essentials of Pathophysiology, 4e

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Disorders of Skin Integrity and Function

C h a p t e r 4 6

Pathogenesis. Four types of melanomas have been identified based on their radial and vertical growth pro- gression: lentigo maligna, superficial spreading, acral lentiginous, and nodular. Radial growth describes the horizontal spread of the melanoma within the epider- mis and superficial dermis. During this initial stage, the tumor seems to lack the ability to metastasize. Lentigo maligna melanomas, superficial spreading melanomas, and acral lentiginous melanomas are tumors that are in the radial growth phase. Lentigo maligna melanomas are flat, slow-growing nevi that may remain in the radial growth phase for several decades. They are seen primar- ily on sun-exposed skin of elderly persons. Superficial spreading melanoma, the most common type of mela- noma, is seen most commonly in persons who sunburn easily and have intermittent sun exposure. It is charac- terized by a raised-edged nevus with lateral growth and a disorderly appearance in color and outline. It typically ulcerates and bleeds with growth. Acral lentiginous melanoma has an appearance similar to that of lentigo maligna, and is seen primarily on the palms, soles, nail beds, and mucous membranes. Its occurrence is unre- lated to sun exposure. After a variable and unpredictable period of time, melanomas shift from a radial to vertical growth phase, during which the tumor cells invade downward into the deeper dermis layers. 11 This growth phase is heralded by the nodular phase and correlates with the emergence of a clone of cells with metastatic potential. Nodular mela- nomas are raised, dome-shaped lesions that can occur anywhere on the body. They are commonly a uniform blue-black color and tend to look like blood blisters. Nodular melanomas tend to rapidly invade the dermis from the start, with no apparent horizontal growth phase. Diagnosis and Treatment. Early detection is critical with malignant melanoma. Regular self-examination of the total skin surface in front of a well-lighted mirror provides a method for early detection. It requires that a person undress completely and examine all areas of the body using a full mirror, handheld mirror, and hand- held hair dryer (to examine the scalp). An ABCD rule has been developed to aid in early diagnosis and timely treatment of malignant melanoma. 64 The ABCD acro- nym stands for a symmetry, b order irregularity, c olor variegation, and d iameter greater than 6 mm (1/4 inch or pencil eraser size). People should be taught to watch for these changes in existing nevi or the development of new nevi, as well as other alterations such as bleeding or itching. Because of the existence of small-diameter mela- nomas (i.e., <6 mm in diameter), it has been suggested that people routinely screen their skin for all possible manifestations of skin cancer. Since their description over 20 years ago, evidence has accumulated to add an E for “evolving” to the ABCD rule. 68 The E for evolving is intended to encourage the recognition of melanomas at an earlier stage by emphasizing the dynamic nature of their growth. Diagnosis of melanoma is based on biopsy findings from a lesion. 64–66 Because most melanomas initially

metastasize to regional lymph nodes, additional infor- mation may be obtained through lymph node biopsy. Consistent with other cancerous tumors, melanoma is commonly staged using the TNM (tumor, lymph node, and metastasis) staging system (see Chapter 7) or the American Joint Committee on Cancer Staging System for Cutaneous Melanoma, in which the tumor is rated 0 to 4 depending on numerous factors, including extent of tumor invasion, ulceration, and metastasis. 64 Ulceration and invasion of the tumor into the deeper skin tissue result in a poorer prognosis. The degree and number of lymph nodes involved correlate well with overall survival. Treatment of melanoma is usually surgical excision, the extent of which is determined by the thickness of the lesion, invasion into the deeper skin layers, and spread to the regional lymph nodes. 64–66 Deep, wide excisions with elective removal of lymph tissue and the use of skin grafts were once the hallmarks of treatment. When diag- nosed in a premetastatic phase, melanoma is now treated in ambulatory settings, lessening the cost and inconve- nience of care. Current capability allows for mapping lymph flow to a regional lymph node that receives lym- phatic drainage from tumor sites on the skin. This lymph node, which is called the sentinel lymph node, is then sampled for biopsy. If tumor cells have spread from the primary tumor to the regional lymph nodes, the sentinel node will be the first node in which tumor cells appear. Therefore, sentinel node biopsy can be used to test for the presence of melanoma cells and determine if radi- cal lymph node dissection is necessary. When nodes are positive, consideration is also given to systemic adjuvant therapy. Although no effective chemotherapy is avail- able for melanoma, interferon alfa-2b is a biologic ther- apy available for adjuvant treatment of melanoma. At this time, however, the use of interferon is controversial. Clinical trials with other therapies, including combina- tion chemotherapies, vaccines, and hyperthermic isola- tion limb perfusion, are ongoing. 64–66 Basal Cell Carcinoma Basal cell carcinoma is a neoplasm of the nonkeratiniz- ing cells of the basal layer of the epidermis. 67 It is the most common invasive cancer in humans; approxi- mately 75% of all skin cancers are basal cell carcino- mas. 67 Basal cell carcinomas have a tendency to occur in fair-skinned persons with a history of significant long- term sun exposure. They are most frequently seen on the head and neck, most often occurring on skin that has hair. Basal cell carcinomas are slow-growing tumors that extend wide and deep if left untreated, but rarely metas- tasize. Advanced lesions are often invasive and ulcer- ative. Risk factors for extensive spread include a tumor diameter greater than 2 cm, location on the central part of the face or ears, long-standing duration, incomplete excision, and perineural or perivascular involvement. Histologically, the tumor cells resemble those in the normal basal layer from the epidermis or follicular epithelium and do not occur on mucosal surfaces. 67