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Malignant Melanoma Workup

  • Author: Winston W Tan, MD, FACP; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Feb 11, 2016
 

Approach Considerations

The diagnosis of melanoma is confirmed by excisional biopsy. Patients with clinically enlarged lymph nodes and no evidence of distant disease should undergo a complete regional lymph node dissection. Sentinel lymph node biopsy is appropriate in selected patients.

Laboratory studies that are indicated include the following:

  • Complete blood cell count (CBC)
  • Comprehensive serum chemistry panel
  • Lactate dehydrogenase (LDH) level

Imaging studies are often obtained in patients with newly diagnosed melanoma, to rule out clinically occult distant disease. Nevertheless, available evidence suggests that preoperative imaging studies have significant costs and offer minimal benefit in most patients with melanoma.[14] One meta-analysis of diagnostic tests used in staging melanoma has shown that ultrasonography is the best imaging study to diagnose lymph node involvement and that positron emission tomography computed tomography scanning (PET/CT) is the best imaging study to look for other sites of metastasis.[15]

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Histologic Findings

Although no single histologic feature is pathognomonic for melanoma, many characteristic features exist. Cytologic atypia virtually always is noted, with enlarged cells containing large, pleomorphic, hyperchromic nuclei with prominent nucleoli. Numerous mitotic figures often are noted.

A pagetoid growth pattern with upward growth of the melanocytes, so they are no longer confined to the basal layer, is considered pathognomonic for melanoma by some pathologists.

Although immunohistochemical stains usually are not necessary for diagnosis, they are generally performed for completeness. Both S-100 and homatropine methylbromide (HMB45) stains are positive in melanoma. The S-100 is highly sensitive, although not specific, for melanoma, while the HMB45 is highly specific and moderately sensitive for melanoma. The 2 stains, in concert, can be useful in diagnosing poorly differentiated melanomas.

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Complete Chemistry Panel

The chemistry panel may give a clue to possible metastatic disease. For example, an elevated alkaline phosphatase level may signal metastasis to the bone or liver, while elevated levels on liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) may represent metastasis to the liver.

Total protein and albumin provide information concerning the overall health and nutritional status of the patient and may afford prognostic information.

Many chemotherapy regimens may be toxic to the kidneys; therefore, a creatinine level is necessary prior to initiation of any treatment.

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Lactate Dehydrogenase Study

The LDH level is elevated in many conditions, including many malignancies. Although LDH elevation is not specific for melanoma, it may be useful at diagnosis and also in the follow-up care of patients with melanoma. A markedly elevated LDH at diagnosis or at a follow-up visit may indicate distant metastases, especially in the lung and liver.

Although the specificity and sensitivity of this test are low, multiple studies show an elevated LDH level to be an independent predictive factor for poor prognosis. LDH level now is considered part of the staging system for melanoma.

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Chest Radiography

For patients with stage I or II disease, a chest radiograph is often obtained, although its result will likely be negative. To date, no studies support obtaining a radiograph in these patients, but a normal chest radiograph finding at diagnosis provides a baseline for future comparison.

Patients with stage III disease, in-transit disease, or local recurrence should have a chest radiograph or CT scan of the chest because the lungs often are the first site of metastatic disease.

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MRI

Magnetic resonance imaging (MRI) of the brain should be obtained during the workup of a patient with known distant metastases to detect additional asymptomatic metastatic disease. This is especially true for patients being considered for high-dose interleukin-2 treatment.

MRI of the brain in patients without known metastatic disease should be reserved for those patients who are symptomatic.

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CT Scanning

Chest CT scan

A chest CT scan should be included in the staging workup of a patient with stage IV disease (ie, the patient with known distant metastases) to detect asymptomatic metastatic lesions.

In patients with stage I, II, or III disease, a chest CT scan should be performed only if clinically indicated.

CT scan of the abdomen

A CT scan of the abdomen often is obtained when evaluating a patient with stage III, locally recurrent, or in transit disease. Although the yield is low, a negative CT scan provides a baseline study for future comparison.

CT scan of the pelvis

This study is indicated only if a patient has local regional recurrence below the waist, is symptomatic, or has known metastatic disease with a history of primary tumors below the waist.

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Positron Emission Tomography

PET scans are not indicated in early-stage disease (Stage I or II), but a PET scan may aid in staging patients with known node involvement or in-transit or satellite lesions. Many studies report that PET scans have greater sensitivity than conventional radiographic studies for the detection of metastatic disease.

One meta-analysis found PET CT scanning to be the best imaging study to utilize for finding other sites of metastasis.[15] In particular, fluorodeoxyglucose (FDG) PET/CT scans are a valuable tool for detecting additional metastasis as part of the preoperative evaluation of patients with advanced and metastatic melanoma.[16] Finally, PET scans often are useful in evaluating the response of metastatic disease to therapy.

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Biopsy of a Suggestive Lesion

A complete excisional biopsy is preferred. The sample should have a 1-3 mm margin of healthy skin and should include all layers of skin and some subcutaneous fat. Although sparing of the deep fascia is not standard in biopsies for suspected melanoma, investigators at the Mayo Clinic recommend this practice in some patients.[17]

If the suggestive lesion is large or situated in a cosmetically sensitive area, an incisional or punch biopsy may be appropriate. The incisional biopsy specimen should be taken from the most abnormal area of the lesion.

A shave biopsy is usually contraindicated, as it may compromise pathologic diagnosis and complete determination of Breslow thickness. However, the National Comprehensive Cancer Network suggests that shave biopsy is acceptable when the index of suspicion is low, and a broad shave biopsy may help optimize diagnostic sampling in cases of lentigo maligna melanoma in situ.[18] In cases where a shave biopsy was done inappropriately, a complete excisional biopsy of the lesion should be performed if possible to determine the depth and extent of the lesion.

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Surgical Excision or Reexcision After Biopsy

Because failure to perform a reexcision after biopsy of a melanoma is associated with a local recurrence rate of as high as 40%, a reexcision must be performed.

Current recommendations for surgical margins of excision are as follows[18] :

  • In situ lesions - 0.5-1 cm margin
  • Lesions ≤ 1 mm in thickness - 1 cm margin
  • Lesions 1.01 - 2 mm in thickness - 1-2 cm margin
  • Lesions 2.01-4 mm in thickness - 2 cm margin
  • Lesions greater than 4 mm in thickness - at least 2 cm margin

A study by Gillgren et al determined that a 2-cm excision provided a safe and reliant resection margin to treat lesions thicker than 2 mm.[19]

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Elective Lymph Node Dissection

Patients with clinically enlarged lymph nodes and no evidence of distant disease should undergo a complete regional lymph node dissection (LND).

For years, patients without clinically enlarged nodes underwent LND. However, studies show that in patients with melanomas that are 1-4 mm thick, LND may not yield a significant survival advantage.

The only patients who seem to benefit from LND are those with lesions 1.1–2 mm thick and who are younger than 60 years. Patients with lesions greater than 4 mm in thickness are widely considered not to benefit from removal of clinically negative nodes.

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Sentinel Lymph Node Biopsy

Lymphatics from any given region on the skin drain to a single lymph node. This node is called the sentinel lymph node and almost always is the first site of nodal involvement when melanoma spreads to regional nodes.

To determine which node is the sentinel node, the following two techniques, often in combination, are used. The combination of the two techniques allows detection of the sentinel node in as many as 98% of cases.

The first technique involves injecting a blue dye at the site of the primary and, through a small incision over the nodal basin, determining the location of the sentinel node. The node is then removed for pathologic evaluation.

The second technique involves a radiolabeled solution injected into the site of the primary and the use of a hand-held gamma detector to determine the location of the sentinel node.

Sentinel lymph node biopsy (SLNB) is now known to offer important prognostic, diagnostic, and therapeutic information.[20]

Guidelines from the National Comprehensive Cancer Network (NCCN) recommend discussing and offering SLNB to patients with stage IB or stage II melanoma that is 0.76-1 mm thick with ulceration or with a mitotic rate ≥1/mm2, or >1 mm thick with any characteristic adverse features. The NCCN recommends discussing and considering SLNB to patients with stage IA melanoma that is 0.76-1 mm thick, with no ulceration and a mitotic rate of 0/mm3.[18] Sentinel node biopsy may be offered either as standard care or in the context of a clinical trial.

The NCCN does not recommend SLNB for patients whose melanoma is 0.75 mm or less in thickness. The NCCN advises that SLNB may be considered if conventional risk factors such as ulceration, high mitotic rate, or lymphovascular invasion are present, but notes that those are very uncommonly found with melanomas that thin.[18]

Joint guidelines from the American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) recommend SLNB for patients with intermediate-thickness melanomas (Breslow thickness 1–4 mm) of any anatomic site. There is less evidence for patients with thick melanomas (T4; Breslow thickness >4 mm), but sentinel lymph node biopsy is recommended for staging and facilitating regional disease control. Evidence supporting routine sentinel lymph node biopsy for patients with thin melanomas (T1; Breslow thickness < 1 mm) is lacking, but it may be an option in selected patients with high-risk features in whom the benefits of staging outweigh the risks of the procedure.

The guidelines recommend completion lymph node dissection (CLND) for all patients with a positive SLNB; CLND achieves good regional disease control. Whether CLND improves survival after a positive sentinel lymph node biopsy is being examined in the ongoing Multicenter Selective Lymphadenectomy Trial II.[21]

In patients whose sentinel lymph node biopsy reveals micrometastases, a randomized phase III trial by Steiner et al found no survival benefit with CLND. No statistically significant differences (ie, 10% or higher) in 5-year recurrence-free survival, distant metastases–free survival, or melanoma-specific survival were evident between 242 patients who underwent CLND and 241 patients who received observation only. At a median follow-up of 35 months, however,  regional lymph node metastases developed in 14.6% of patients in the observation group versus 8.3% of those in the CLND group.[22]

Cadili et al reported that the likelihood of non–sentinel lymph node metastasis can be predicted on the basis of total metastasis within the sentinel lymph node. Their data showed that patients with ≥5 mm of metastasis have a 30% risk of metastasis. In contrast, those with less than 2 mm of total sentinel lymph node metastasis are unlikely (<3.67% likelihood) to harbor metastasis in non-sentinel nodes, and those patients may not benefit from additional nodal dissection.[23]

Go to Sentinel Lymph Node Biopsy in Patients With Melanoma for complete information on this topic.

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Contributor Information and Disclosures
Author

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, Texas Medical Association, American Society of Clinical Oncology, Philippine Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Philip Schulman, MD Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center

Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

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A 1.5-cm melanoma with characteristic asymmetry, irregular borders, and color variation.
Malignant melanoma. Image courtesy of Hon Pak, MD.
Lentigo maligna melanoma, right lower cheek. The centrally located erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ). Image courtesy of Susan M. Swetter, MD.
 
 
 
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