eMedicine Specialties > Oncology > Carcinomas of the Skin

Malignant Melanoma: Differential Diagnoses & Workup

Author: Winston W Tan, MD, Assistant Professor of Medicine, Mayo Medical School; Consulting Staff, Mayo Group Practices
Contributor Information and Disclosures

Updated: Nov 23, 2009

Differential Diagnoses

Basal Cell Carcinoma
Lentigo Maligna Melanoma
Mycosis Fungoides

Other Problems to Be Considered

Benign melanocytic lesions
Dysplastic nevus
Squamous cell carcinoma
Metastatic tumors to the skin
Blue nevus
Epithelioid (Spitz) tumor
Pigmented spindle cell tumor
Halo nevus
Atypical fibroxanthoma
Pigmented actinic keratosis
Sebaceous carcinoma
Histiocytoid hemangioma

Workup

Laboratory Studies

• CBC count
• Chemistry panel (complete)
  • The chemistry panel may give a clue to possible metastatic disease. For example, an elevated alkaline phosphatase level may signal metastatic disease to the bone or liver, while elevation of liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) may represent metastatic disease 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.
• Lactate dehydrogenase
  • Lactate dehydrogenase (LDH) level is elevated with many conditions, including many malignancies. Although LDH 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.

Imaging Studies

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.³

• Chest radiograph
  • 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.
• CT scan or MRI of the brain
  • 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.
• 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.
• PET scan:
  • A positron emission tomography (PET) scan may aid in staging patients with known node disease or in transit or satellite lesions. Many studies report a greater sensitivity with PET scans compared with conventional radiographic studies for the detection of metastatic disease.
  • PET scans often are useful in evaluating the response of metastatic disease to therapy.
  • PET scans are not indicated in early-stage disease (Stage I or II).

Procedures

• Biopsy of a suggestive lesion
  • A complete excisional biopsy is preferred and should include a 1-2 mm margin of healthy skin, to include all layers of skin and some subcutaneous fat.
  • If the suggestive lesion is large or situated in a cosmetically sensitive area, an incisional or punch biopsy may be appropriate. The incisional biopsy should be taken from the most abnormal area of the lesion.
  • Because all layers of the skin must be included in the biopsy, a shave biopsy is contraindicated.
  • In some cases where a shave biopsy was done on a lesion, a complete excisional biopsy should be performed if possible to determine the depth and extent of the lesion.
• Surgical excision or reexcision after biopsy
  • Because failure to perform a reexcision after biopsy of a melanoma is associated with a local recurrence rate as high as 40%, a reexcision must be performed.
  • Current recommendations for margins of excision are as follows:
    • Lesions less than 1 mm in thickness - 1 cm margin
    • Lesions 1-4 mm in thickness - 2 cm margin
    • Lesions greater than 4 mm in thickness - at least 2 cm margin
• 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. Recent 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.
• Sentinel lymph node dissection
  • 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 2 techniques, often in combination, are used. The combination of the 2 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 node biopsy is now known to offer important prognostic, diagnostic, and therapeutic information.⁴
    • Guidelines from the National Comprehensive Cancer Network (NCCN) suggest that it is reasonable to offer sentinel lymph node biopsy to patients with thick melanoma (4 mm or greater), in whom the probability of a positive sentinel node is 30-40% and in whom sentinel lymph node status is a strong independent predictor of outcome.⁵ Sentinel node biopsy may be offered either as standard care or in the context of a clinical trial.
    • The NCCN does not recommend sentinel lymph node biopsy for patients with in situ melanoma (stage 0) or stage IA melanoma that is 1 mm or less with no adverse features. Although there appears to be a subset of patients with thin melanoma who are at sufficient risk for a positive sentinel lymph node to justify a biopsy, there is not yet clear consensus regarding which factors best predict this risk; possible factors include  thickness over 0.75 mm, high mitotic rate, and young patient age; other possible factors include positive deep margins and lymphovascular invasion.⁶

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.

Staging

The staging system for cutaneous melanoma was revised by the American Joint Committee on Cancer (AJCC) in early 2002.^7,8

• Clark staging
  • Level I - All tumor cells above basement membrane (in situ)
  • Level II - Tumor extends into papillary dermis
  • Level III - Tumor extends to interface between papillary and reticular dermis
  • Level IV - Tumor extends between bundles of collagen of reticular dermis (extends into reticular dermis)
  • Level V - Tumor invasion of subcutaneous tissue
• Breslow classification (thickness)
  • Less than or equal to 0.75 mm
  • 0.76-1.5 mm
  • 1.51-4 mm
  • Greater than or equal to 4 mm
• AJCC groupings based on TNM classification
  • Stage 0 - Tis, N0, M0
  • Stage 1A - T1a, N0, M0
  • Stage 1B
    • T1b, N0, M0
    • T2b, N0, M0
  • Stage IIA
    • T2b, N0, M0
    • T3a, N0, M0
  • Stage IIB
    • T3b, N0, M0
    • T4a, N0, M0
  • Stage IIC - T4b, N0, M0
  • Stage III - Any T, N 1-3, M0
  • Stage IIIA
    • pT1-4a, N1a, M0
    • pT1-4a, N2a, M0
  • Stage IIIB
    • pT1-4b, N1a, M0
    • pT1-4b, N2a, M0
    • pT1-4a, N1b, M0
    • pT1-4a, N2b, M0
    • pT1-4a/b, N2c, M0
  • Stage IIIC
    • pT1-4b, N1b, M0
    • pT1-4b, N2b, M0
    • Any T, N3, M0
  • Stage IV - Any T, Any N, Any M
• T classification (thickness)
  • TX - Primary tumor cannot be assessed ( shave biopsy, regressed primary)
  • Tis Melanoma in situ
  • T1 -£ 1.0 mm (a: without ulceration, b: with ulceration)
  • T2 - 1.01-2.0 mm (a: without ulceration, b: with ulceration)
  • T3 - 2.01-4.0 mm (a: without ulceration, b: with ulceration)
  • T4 - <4.0 mm (a: without ulceration, b: with ulceration)
• N classification
  • N1 - 1 lymph node; a: micrometastasis (clinically occult), b: macrometastasis (clinically apparent)
  • N2 - 2-3 lymph nodes; a: micrometastasis, b: macrometastasis, c: in transit met(s), satellite(s), without metastatic lymph nodes
    • N2a - 2-3 nodes positive for micrometastasis
    • N2b - 2-3 nodes positive for macrometastasis
    • N2c - In transit met(s) or satellite(s) without metastatic nodes
  • N3 - 4 or more metastatic nodes or matted nodes or in-transit metastases or satellite(s) with metastatic node(s).
  • Note: Micrometastases are diagnosed after elective or sentinel lymphadenectomy. Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.
• M classification
  • M1a - Distant skin, subcutaneous, or nodal metastases, normal LDH level
  • M1b - Lung metastases, normal LDH level
  • M1c - All other visceral metastases or any distant metastases with an elevated LDH level

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