Malignant Melanoma Guidelines 

Updated: Jan 18, 2016
Author: Wesley Wu, MD; Chief Editor: Dirk M Elston, MD 

Skin Cancer Screening

In 2009, the U.S. Preventive Services Task Force (USPSTF) concluded there is not enough evidence to recommend for or against routine screening (total body examination by a primary care physician or patient self-examination) for early detection of skin cancers in the adult general population.[1] However, those recommendations are currently in the process of being updated.

The USPSTF did make the following clinical practice recommendations:

  • Physicians should remain aware that fair-skinned men and women aged 65 and older, and people with atypical moles or more than 50 moles, are at greater risk for melanoma; other risk factors for skin cancer include family history and a considerable history of sun exposure and sunburns

  • When performing physical examinations for other reasons, remain alert for skin lesions with malignant features

  • Asymmetry, border irregularity, color variability, diameter greater than 6 mm (ABCD criteria), or rapidly changing lesions are features associated with an increased risk for cancer

  • All suspicious lesions should be biopsied


Clinical Presentation and Workup

The National Comprehensive Cancer Network (NCCN) supports the concept that most melanoma recurrences are diagnosed clinically. Current NCCN guidelines state that no further workup (ie, baseline laboratory tests and imaging studies) is required in stage 0 (melanoma in situ) and for asymptomatic patients with stage IA, IB, or IIA melanoma. (Physician Quality Reporting System (PQRS) measure #224 concerns overutilization of imaging studies in melanoma.) Imaging (CT scanning, PET, MRI) should be obtained only as clinically indicated to evaluate specific signs or symptoms in stage IIB and IIC patients with higher-risk melanoma.[2]

Guidelines established by the American Academy of Dermatology (AAD) in 2011 are as follows[3] :

  • Baseline tests are not recommended in asymptomatic patients with any stage of primary melanoma (IA-IIC)

  • Regular clinical follow-up and interval patient self-examination of skin and regional lymph nodes are the most important means of detecting recurrent disease or new primary melanoma

  • Findings from history and physical examination should direct need for further studies to detect local, regional, and distant metastasis

  • Surveillance laboratory tests and imaging studies in asymptomatic patients with melanoma have low yield for detection of metastatic disease and are associated with relatively high false-positive rates

Current NCCN guidelines do not recommend surveillance (follow-up) laboratory or imaging studies for asymptomatic patients with stage IA, IB, and IIA melanoma (ie, tumors ≤4 mm depth). Imaging studies (chest radiograph, CT and/or PET-CT) should be obtained as clinically indicated for confirmation of suspected metastasis or to delineate the extent of disease.[2]

The NCCN advises that imaging studies may be considered to screen for recurrent/metastatic disease in patients with stage IIB-IV disease, although this recommendation remains controversial. Routine laboratory or radiologic imaging in asymptomatic melanoma patients of any stage is not recommended after 5 years of follow-up.[2]

While abnormal laboratory test results are rarely the sole indicator of metastatic disease, serum lactate dehydrogenase (LDH) levels were incorporated into the American Joint Committee on Cancer (AJCC) 2002 melanoma staging guidelines for the classification of stage IV (distant) disease. Elevated LDH levels are associated with worse survival in this subgroup and remain a powerful predictor of survival in the 2009 American Joint Commission for Cancer (AJCC) Cancer Staging Manual (7th Ed) for melanoma of the skin.[4]


Sentinel Lymph Node Dissection

The melanoma guidelines from the National Comprehensive Cancer Network (NCCN) do not recommend sentinel lymph node biopsy for patients with in situ melanoma (stage 0).[2]

Evidence supporting routine sentinel lymph node biopsy for patients with thin melanomas (T1; Breslow thickness < 1 mm) is lacking and recommendations remain controversial. The NCCN does not recommend sentinel lymph node biopsy for patients with lesions 0.75 mm or thinner.{ref 2} However, the American Academy of Dermatology (AAD) recommends consideration of sentinel lymph node biopsy in patients with lesions, including those less than 0.76 mm, with any of the following high-risk features[3] :

  • Ulceration

  • Mitosis

  • Angiolymphatic invasion

  • Positive deep margin

  • Young patient age

However, recent data suggest that the presence of a single mitotic figure may not correlate well with sentinel node status in thin lesions.[5] In addition, the presence of regression in thin lesions is associated with a lower risk of nodal metastasis.[6]

The 2012 joint guidelines from the American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO), as well as the 2009 American Joint Commission for Cancer (AJCC) Melanoma Staging and Classification Committee (BALCH), recommend sentinel lymph node biopsy for patients with intermediate-thickness melanomas (Breslow thickness 1–4 mm) at 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.

The guidelines also recommend completion lymph node dissection (CLND) for all patients with a positive sentinel lymph node biopsy. CLND achieves good regional disease control; however, its impact on disease-free survival remains to be clarified in the ongoing Multicenter Selective Lymphadenectomy Trial II.[7]


Mohs Surgery

The American Academy of Dermatology 2011 guidelines state that Mohs micrographic surgery (MMS) is an acceptable technique for excision of melanoma in situ and lentigo maligna.[7] The National Comprehensive Cancer Network (NCCN) accepted the utility of MMS for melanoma in situ, revising their guidelines of surgical margins for melanoma in situ.[2]

The NCCN cites an MMS study that employed MMS enhanced by immunohistochemical staining as the primary treatment modality for melanoma in situ, which resulted in 99% removal of melanoma in situ when a total surgical margin of 9 mm was used, versus an 86% rate of removal with 6-mm margins. The stain comprised antibodies to a melanoma antigen recognized by T cells (MART-1).[2, 8]

The appropriate-use criteria for MMS from the AAD, American College of Mohs Surgery (ACMS), American Society for Dermatologic Surgery Association (ASDSA), and the American Society for Mohs Surgery (ASMS) further state that MMS is appropriate for all recurrent melanoma in situ and lentigo maligna, as well as primary lesions at the following sites[9] :

  • Head

  • Neck

  • Hands

  • Feet

  • Pretibial surface

  • Nails

  • Ankles


Wide Excision Surgical Margins

For wide excision of primary melanoma, the NCCN and AAD practice guidelines agree on the following surgical margin recommendations for primary melanoma[2, 3] :

  • Tumor in situ – Margin size 0.5-1.0 cm

  • Tumor smaller than 1 mm – Margin size 1 cm

  • Tumor 1-2 mm – Margin size 1-2 cm

  • Tumor 2-4 mm – Margin size 2 cm

  • Tumor greater than 4 mm – Margin size at least 2 cm


Radiation Therapy for Melanoma

NCCN guidelines recommend consideration of radiation therapy in the following situations[2] :

  • Primary disease: As adjuvant treatment in selected patients with factors that include deep desmoplastic melanoma with narrow margins, extensive neurotropism, or locally recurrent disease

  • Regional disease: As adjuvant treatment following resection of category 2B nodes and LDH < 1.5 times the upper limit of normal, and extranodal tumor extension; as palliative treatment for unresectable disease

  • Metastatic disease: As either adjuvant or primary treatment for brain metastases


Treatment for Advanced Melanoma

NCCN recommendations for treatment of melanoma stage IV disease with distant metastasis include the following[2] :

  • Treatment depends on whether melanoma is limited (resectable) or disseminated (unresectable)

  • In limited disease, resection is recommended; alternatively, observation or systemic therapy may be chosen

  • Treatment for limited disease includes clinical trial enrollment or systemic therapy For patients with unresectable disease without brain metastases, treatment includes systemic therapy; patients with brain metastases require treatment of the central nervous disease

Preferred regimens for systemic therapy, according to the NCCN guidelines, are as follows[2] :

  • Ipilimumab

  • Dabrafenib plus trametinib

  • Pembrolizumab

  • Nivolumab

Other active regimens include the following, among others[2] :

  • Vemurafenib

  • Dabrafenib

  • Trametinib

  • High-dose interleukin-2 (IL-2)

  • Dacarbazine-, temozolomide-, or paclitaxel-based chemotherapy


Follow-up for Melanoma Cancer Survivors

Follow-up guidelines from the National Comprehensive Cancer Network are listed below.[2]

Follow-up for stage 0 in situ is as follows:

  • At least annual skin examination for life

  • Educate patient in monthly self-examination of skin

Follow-up for stage IA is as follows:

  • History and physical examination (H&P), with emphasis on lymph nodes and skin, every 3-12 mo for 5 y, then annually as clinically indicated

  • At least annual skin examination for life

  • Educate patient in monthly self-examination of skin and lymph nodes

Follow-up for stage IB-IV (patients with no evidence of disease) is as follows:

  • H&P (with emphasis on nodes and skin) every 3-6 mo for 2 y, then every 3-12 mo for 2 y, then annually as clinically indicated

  • Chest radiography, lactate dehydrogenase (LDH) level, and complete blood cell count (CBC) every 6-12 mo (optional)

  • Routine imaging is not recommended for stage IB or IIA disease

  • Computed tomography (CT) scans to follow up for specific signs and symptoms

  • Consider CT and/or PET scans to screen stage IIB and higher for recurrent/metastatic disease every 3 to 12 months

  • At least annual skin examination for life

  • Educate patient in monthly self-examination of skin and lymph nodes