Chapter 083. Cancer of the Skin (Part 6) Biopsy Any pigmented cutaneous lesion that has changed in size or shape or has other features suggestive of malignant melanoma is a candidate for biopsy. The recommended technique is an excisional biopsy, as that facilitates pathologic assessment of the lesion, permits accurate measurement of thickness if the lesion is melanoma, and constitutes treatment if the lesion is benign. For large lesions or lesions on anatomic sites where excisional biopsy may not be feasible (such as the face, hands, or feet), an incisional biopsy through the most nodular or darkest area of the lesion is acceptable; this should include the vertical growth phase of the primary tumor, if present. Incisional biopsy does not appear to facilitate the spread of melanoma. Staging Once the diagnosis of malignant melanoma has been confirmed, the tumor must be staged to determine prognosis and treatment. The history should probe for evidence of metastatic disease, such as malaise, weight loss, headaches, visual difficulty, or bone pain. The physical examination should be directed especially to the skin, regional draining lymph nodes, central nervous system, liver, and spleen. In the absence of signs or symptoms of metastasis, few laboratory or radiologic tests are indicated for staging purposes. No tests or scans are routinely indicated unless the history or physical examination suggests metastasis to a specific organ. Once signs of metastasis exist, favored sites of spread, such as the liver, lungs, bone, and brain, should be evaluated. Patients are classified into four stages (Table 83-3). Melanoma: Treatment Surgical Management For a newly diagnosed cutaneous melanoma, wide surgical excision of the lesion with a margin of normal skin is necessary to remove all malignant cells and minimize possible local recurrence. The appropriate width of the margin is a source of controversy. A World Health Organization trial that prospectively randomized between 1- and 3-cm margins in 612 patients with thin malignant melanomas (≤2 mm thick) reported that the narrower margin resulted in higher rates of local recurrence but no difference in rates of nodal or distant metastases, disease-free survival, or overall survival. Another large randomized trial comparing 2- or 4-cm surgical margins for intermediate-thickness lesions (1–4 mm thick) also found no significant differences in overall survival. The following margins can be recommended for primary melanoma: in situ: 0.5 cm; invasive up to 1 mm thick: 1.0 cm; >1 mm: 2.0 cm. For lesions on the face, hands, and feet, strict adherence to these margins must give way to individual considerations about the constraints of surgery and minimization of morbidity. In all instances, however, inclusion of subcutaneous fat in the surgical specimen facilitates adequate thickness measurement and assessment of surgical margins by the pathologist. Sentinel Node Biopsy Sentinel node biopsy (SLNB) has replaced elective regional nodal dissection for the evaluation of regional nodal status. The initial draining node(s) from the primary site is/are identified by injecting a blue dye and a radioisotope around the primary site. The initial draining node(s) is/are then identified by inspection of the nodal basin for the blue stained node and/or the node with high uptake of the radioisotope. The identified nodes are removed and subjected to careful histopathologic processing with serial section hematoxylin and eosin stains as well as immunohistochemical stains that identify melanocytes. Sentinel lymph node examination is a valuable staging tool, and in the instance of a negative biopsy, SLNB may obviate the need for complete nodal dissection. Patients with lesions <0.75 mm thick have an excellent prognosis and are not candidates for SLNB unless other high-risk features are present (ulceration, shave biopsy with base involved, etc.). At the other extreme, patients with lesions >4 mm thick have such a high risk for distant metastases that controlling nodal disease may not alter the ultimate clinical outcome. A subset of patients with lesions of intermediate thickness may have a survival benefit from regional node dissection. SLNB is of value in selecting patients who may benefit from adjuvant therapy. Survival benefit of SLNB remains to be proven. Adjuvant Therapy for Nodal Disease For patients who are free of disease but at high risk for metastases, adjuvant therapy that complements surgery is needed to destroy occult micrometastases, prolong disease-free survival, and improve the cure rate. Many strategies have been tried unsuccessfully. However, adjuvant interferon (IFN) α2b may be capable of improving disease-free and overall survival in patients with nodal metastases (stage III disease). The U.S. Food and Drug Administration has approved a high- dose IFN adjuvant protocol consisting of 20 million units per square meter intravenously 5 days a week for 4 weeks followed by 10 million units per square meter subcutaneously three times a week for 11 months. In a large fraction of patients, these doses of IFN are associated with severe toxicity, including a flulike illness and decline in performance status. The toxicity in most patients reverses promptly with lower doses and when therapy is stopped. . Chapter 083. Cancer of the Skin (Part 6) Biopsy Any pigmented cutaneous lesion that has changed in size or shape or has other features suggestive of malignant melanoma. excision of the lesion with a margin of normal skin is necessary to remove all malignant cells and minimize possible local recurrence. The appropriate width of the margin is a source of controversy darkest area of the lesion is acceptable; this should include the vertical growth phase of the primary tumor, if present. Incisional biopsy does not appear to facilitate the spread of melanoma.