A patient with newly diagnosed melanoma should undergo a comprehensive history that includes assessment of age, gender, personal or family history of melanoma or other malignancy as well as history of any nevus syndromes. The patient should also be assessed for any other significant medical and surgical history or issues, medications used, and allergies.

History of sun exposure and use of tanning beds, if any, should also be obtained. A thorough history may also provide clinical clues as to the extent of disease present at diagnosis. Symptoms such as worsening headaches or abdominal cramps may suggest distant metastatic disease and warrant additional workup.

A physical examination is extremely important in the newly diagnosed patient with melanoma. If a biopsy has been performed, the anatomic site and orientation of the biopsy should be documented along with the presence or absence of any residual pigmented lesion.

Skin and soft tissue between the primary site and draining regional nodal basin(s) should be examined for any signs of satellite metastases or in-transit disease. Melanoma most commonly metastasizes via regional lymphatics to regional lymph nodes. Nonetheless, because melanoma may metastasize to both regional and distant nodes, all palpable lymph nodes should be carefully examined in the new melanoma patient, including cervical, supraclavicular, axillary, epitrochlear, inguinal, and popliteal nodes. For patients with a melanoma in a region of ambiguous drainage (typically considered to be the head and neck and trunk regions), multiple nodal basin drainage is possible. Given the importance of the lymphatics in melanoma, meticulous attention to the lymphatic exam is essential. Evidence of lymphedema in the melanoma-bearing extremity may also suggest regional nodal disease.

It is imperative to confirm the specific site(s) of any primary melanoma to be treated. Although this may seem obvious, many patients have had concomitant and/or prior skin biopsies, and further clarification with source information, including pre-biopsy photographs and/or direct consultation with the referring clinician, may be necessary. Because biopsy sites may heal prior to treatment, photographic images are often obtained to document location(s) of all biopsy sites for which treatment is/may be planned.

The clinician should document the presence of any lymphadenopathy along with details such as firm, fixed, or matted nodes. Clinically suspicious lymph nodes should be evaluated by fine needle aspiration biopsy (often performed with ultrasound guidance) and cytologic analysis. Biopsy-proven regional metastasis renders a sentinel node biopsy (SNB) procedure unnecessary to diagnose stage III disease in the involved basin.

Importantly, palpable “reactive” lymphadenopathy may sometimes develop following biopsy of the primary melanoma, thus highlighting the importance of pathologic confirmation of metastatic melanoma before definitive treatment of the basin—for example, lymphadenectomy—is considered.

Newly diagnosed melanoma patients should also undergo a head-to-toe skin examination to identify the presence of other suspicious skin lesions. Although it is beyond the scope of this section to review biopsy techniques in detail, an appropriate biopsy should include the epidermis, dermis, and at least a cuff of subdermal fat. This allows the dermatopathologist to accurately report the essential components of primary melanoma tumor histopathologic microstaging, including, at a minimum, Breslow thickness (in millimeters), presence or absence of ulceration, mitotic rate, Clark level, status of peripheral and deep margins, and presence or absence of satellite lesions.

When signs and/or symptoms are suggestive of additional disease, a well-performed physical examination may raise suspicion for distant metastasis. Particular attention should be paid to the neurologic examination, assessing for any localizing symptoms or mental status changes. The finding of hepatomegaly, abdominal mass, or a rectal exam significant for mass or occult blood should prompt further workup. Finally, distant dermal or subcutaneous nodules or distant adenopathy also warrant investigation.

Treatment planning for patients with primary melanoma is based largely on primary tumor histologic microstaging.

In the absence of symptoms, the use of imaging studies as part of a staging workup has not been shown to significantly impact survival or the treatment algorithm of the newly diagnosed, clinically node-negative melanoma patient. For asymptomatic preoperative stages I and II melanoma patients, preoperative cross-sectional imaging has a very low yield.² In one study, only 1 of 344 (0.3%) studies correlated with confirmed melanoma metastasis; no significant impact on proposed surgical management or staging was noted.³

Even among asymptomatic microscopic stage III patients (i.e., sentinel-node positive), cross-sectional imaging studies infrequently identify distant metastatic melanoma.⁴ Although positron emission tomography (PET)/computed tomography (CT) generally includes images of the extremities, regions not typically imaged during standard CT or magnetic resonance imaging (MRI), a benefit for routine use of PET/CT has yet to be demonstrated in this patient population.

In the otherwise asymptomatic patient with clinically palpable adenopathy, the detection rate of asymptomatic distant metastasis is higher and baseline imaging for staging (CT, PET/CT, MRI) is recommended.⁵

There is no specific tumor marker or biochemical parameter that has been validated and employed for melanoma screening or recurrence. Elevated serum lactate dehydrogenase (LDH) level is an adverse prognostic factor in patients with distant metastatic melanoma and is included in the American Joint Committee on Cancer (AJCC) staging system for stage IV disease. Patients with elevated serum LDH levels LDH levels are classified as M1c regardless of distant anatomic site(s) involved.⁶