Management of Primary Cutaneous Melanoma

Publication Date: November 1, 2018
Last Updated: March 14, 2022

Recommendations

Diagnostic biopsy of suspected melanoma

Preferred biopsy technique is a narrow excisional/ complete biopsy with 1- to 3-mm margins that encompass the entire breadth of lesion and is of sufficient depth to prevent transection at the base. This may be accomplished by fusiform/elliptical or punch excision or deep shave/saucerization removal to depth below the anticipated plane of the lesion. (B)
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Partial/incomplete sampling (incisional biopsy) is acceptable in select clinical circumstances such as facial or acral location, very large lesion, or low clinical suspicion or uncertainty of diagnosis. (B)
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Narrow-margin excisional biopsy may be performed if an initial partial biopsy is inadequate for diagnosis or microstaging, but it should not generally be performed if the initial specimen meets the criteria for consideration of sentinel lymph node biopsy. (B)
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Clinical information to be provided to the pathologist

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Recommended clinical information to be provided to the pathologist
Essential Strongly recommended Optional
Age of patient Biopsy intent (excisional/complete vs partial/incomplete) and technique (elliptical, punch shave/saucerization) Clinical description/level of suspicion for melanoma/prior change or biopsy (if applicable)
Sex Size of lesion Dermoscopic features (with or without photograph)
Anatomic location (including laterality) Clinical impression/differential diagnosis
Macroscopic satellites
Clinical photograph (if possible)
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Recommended histologic features of primary cutaneous melanoma for inclusion in the pathology report
Essential Optional
Size of specimen Gross description of lesion
Tumor thickness (Breslow), nearest 0.1 mm Angiolymphatic invasion/lymphovascular invasion
Ulceration Histologic subtype
Dermal mitotic rate; ‘‘hotspot’’ method; No. of mitoses/mm2 Neurotropism/perineural invasion
Peripheral and deep margin status (negative/positive [broad vs. focal transection at deep margin]) Regression
Microsatellitosis Tumor category for staging
Tumor-infiltrating lymphocytes
Anatomic level of invasion (Clark level)
Vertical growth phase
Microsatellitosis (B)
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Pathology report

  • Clinical information
(C)
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  • Tumor (Breslow) thickness
(A)
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  • Ulceration
(A)
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  • Mitotic rate
(A)
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  • Level of invasion (Clark level)
(B)
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  • Angiolymphatic invasion
(B)
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  • Histologic subtype
(B)
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  • Neurotropism/perineural invasion
(C)
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  • Regression
(B)
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  • Tumor-infiltrating lymphocytes
(B)
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Against testing for oncogenic mutations in the absence of metastatic melanoma or outside of a clinical study. (C)
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Diagnostic, prognostic, and therapeutic molecular testing

Ancillary diagnostic molecular techniques (eg, CGH, FISH, GEP) may be used for equivocal melanocytic neoplasms. ()
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Routine molecular testing, including GEP, for prognostication is discouraged until better use criteria are defined. The application of molecular information for clinical management (eg, sentinel lymph node eligibility, follow-up, and/or therapeutic choice) is not recommended outside of a clinical study or trial. ()
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Testing of the primary CM for oncogenic mutations (eg, BRAF, NRAS ) is not recommended in the absence of metastatic disease. (undefined)
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Surgical management of primary cutaneous melanoma

Surgical excision with histologically negative margins is the recommended and first-line treatment for primary CM of any thickness, as well as for melanoma in situ. Surgical margins should be based on tumor thickness. (A)
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Surgical margins for invasive CM should be ≤1 cm and ≤2 cm measured clinically around the primary tumor, although margins may be narrower to accommodate function and/or anatomic location. Depth of excision is recommended to (but not including) the fascia.
  • MIS
(B)
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  • ≤1.0 mm
(A)
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  • >1.0 to 2.0 mm
(A)
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  • >2.0 mm
()
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For melanoma in situ, wide excision with 0.5- to 1.0-cm margins is recommended; MIS, LM type, may require >0.5-cm margins to achieve histologically negative margins because of subclinical extension. (B)
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Sentinel lymph node biopsy, when indicated, should be performed before wide excision of the primary tumor, and in the same operative setting, whenever possible. (C)
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Mohs micrographic surgery or staged excision with paraffin-embedded permanent sections may be utilized for MIS, LM type, on the face, ears, or scalp for tissue-sparing excision and exhaustive histologic assessment of peripheral margins. ()
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For MIS, LM type, permanent section analysis of the central MMS debulking specimen is recommended to identify and appropriately stage potential invasive CM. If invasive CM is identified on a MMS section intraoperatively, the tissue should be submitted for formal pathology review. ()
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Sub--1-cm margins (by either WE or MMS) for primary invasive melanomas at anatomically constrained sites (eg, head and neck, acral sites) are generally not recommended until further studies are available. (C)
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Sentinel lymph node biopsy

For all SLNB-eligible patients, careful discussion of the risks and benefits of the procedure involving surgical oncology input is recommended. ()
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SLNB is not recommended for patients with MIS or for most T1a CM (<0.8 mm without ulceration per the eighth edition of the AJCC staging system). ()
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SLNB should be discussed and offered in appropriate patients with CM >1 mm thickness (≥T2a), including T4 CM. ()
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In patients with T1b CM (<0.8 mm with ulceration or 0.8-1.0 mm with or without ulceration per the eighth edition of the AJCC staging system), SLNB should be discussed and considered, though rates of SLN positivity are still relatively low. ()
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SLNB may be considered for T1a CM if other adverse features are present, including young age, presence of lymphovascular invasion, positive deep biopsy margin (if close to 0.8 mm), high mitotic rate, or a combination of these factors. ()
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Interdisciplinary collaboration involving surgical and medical oncologists is recommended for discussion of possible completion lymph node dissection vs. regional nodal ultrasound surveillance in the event of a positive SLNB. ()
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SLNB

  • No SLNB for MIS or T1a melanoma
  • Discussion of SLNB for T1a melanoma (<0.8 mm) if other adverse features are present
  • Discussion of SLNB for T1b CM (<0.8 mm with ulceration and 0.8-1.0 mm with or without ulceration)
  • Discussion and offering of SLNB for CM >1 mm thickness (≥T2a)
(B)
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Discussion of SLNB risks vs. benefits with patients

Interdisciplinary discussion regarding possible CLND or ultrasound surveillance if positive SLNB (C)
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Baseline and surveillance studies and follow-up

Baseline radiologic imaging and laboratory studies are not recommended for asymptomatic patients with newly diagnosed stage 0-II primary CM. (A)
Radiologic imaging and laboratory studies for CM at baseline should be performed only to evaluate specific signs or symptoms of synchronous metastasis (regional nodal or distant).
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The use of LN ultrasound is encouraged at baseline or in surveillance in the setting of an equivocal LN on physical examination, and for surveillance when:
  • The patient meets criteria for SLNB but does not undergo the procedure;
  • SLNB is not possible or not technically successful (eg, because of failure of lymphoscintigraphic dye migration and inability to identify a draining SLN); or
  • CLND is not performed in the setting of a positive SLNB; and
  • When radiology expertise in the use of nodal ultrasound surveillance for CM is available.
(A)
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Regular clinical follow-up is recommended as the most important means of detecting CM recurrence. Findings from the history (review of systems) and physical examination should direct the need for further radiologic or laboratory studies to detect local, regional, and distant metastatic disease. (A)
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Collaboration with medical oncology is recommended for patients with high-risk CM (stage IIB and IIC) and those with a positive SLNB result for discussion of surveillance imaging and clinical comanagement. (C)
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Surveillance follow-up schedule and consideration of radiographic imaging varies according to the risk of disease recurrence (as determined by stage of disease and other factors) and risk of new primary CM (determined by mole pattern, presence of atypical nevi, and family history). Laboratory studies are not recommended for surveillance of asymptomatic patients with CM. ()
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Patient education on self-examination of the skin and LN for the detection of recurrent disease or new primary CM is recommended. (A)
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There is insufficient evidence to recommend routine molecular profiling assessment for baseline prognostication. Evidence is lacking that molecular classification should be used to alter patient management outside of current guidelines (eg, NCCN and AAD). The criteria for and the utility of prognostic molecular testing, including GEP, in aiding clinical decision making (eg, SLNB eligibility, surveillance intensity, and/or therapeutic choice) needs to be evaluated in the context of clinical study or trial. (C)
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NONSURGICAL MANAGEMENT OF MIS, LM TYPE

Imiquimod or RT

Topical imiquimod 5% cream may be used as second-line treatment for MIS, LM type, when surgery is not possible at the outset (primary setting) or when optimal surgery has been performed (adjuvant setting). (B)
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Careful discussion of the associated risks, benefits, and uncertainties of nonsurgical treatment should take place with the patient and family. ()
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For nonsurgical candidates, RT may be utilized as a second-line therapy for MIS, LM type, though its use is uncommon in the United States. (C)
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The use of superficial brachytherapy for MIS, LM type, is not recommended. (C)
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Adjuvant RT after WE may be used for desmoplastic CM with high-risk features (eg, Breslow thickness [4 mm, Clark level V, extensive neurotropism/perineural invasion, head and neck location, and/or narrow deep margin resection). (B)
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Consultation with a radiation oncologist is recommended to discuss the associated risks and potential benefits of RT. (C)
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PREGNANCY AND MELANOMA

Management of CM and pregnancy

In a pregnant woman with CM, a tailored, multidisciplinary approach to care that involves the obstetrician and CM specialists relevant to the patient’s stage of disease is recommended. A diagnosis of CM during pregnancy does not alter prognosis or outcome for the woman; however, work-up and treatment must take the safety of the fetus into consideration. (C)
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In women with a history of CM, a prolonged waiting period before subsequent pregnancy is not recommended. Factors that affect disease recurrence, including CM thickness and stage, as well as age and fertility of the mother, should determine whether a woman with a history of CM should delay becoming pregnant and for how long. (B)
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The approach to melanocytic nevi in the pregnant woman should be identical to that in the nonpregnant patient. Any changing nevus during pregnancy should be evaluated and subjected to biopsy if clinically and/or dermoscopically concerning. (C)
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Exogenous hormones (eg, oral contraceptives and hormone-containing contraceptive devices/implants, postmenopausal hormone replacement therapy, or hormones associated with assisted reproductive technology) may be used in women in whom CM has been diagnosed. (B)
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GENETIC COUNSELING FOR PATIENTS WITH FAMILIAL MELANOMA AND MULTIGENE TESTING

Genetic counseling of patients with CM

Cancer risk counseling by a qualified genetic counselor is recommended for patients with CM who have:
  • A family history of invasive CM or pancreatic cancer (≥3 affected members on 1 side of the family)
  • Multiple primary invasive CM (≥3), including 1 early-onset tumor (at age <45 y)
  • ≥1 MBAIT and a family history of mesothelioma, meningioma, and/or uveal melanoma
  • ≥2 MBAITs
(-)
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Dermatologic toxicities of newer drugs for advanced CM (AJCC stages III and IV)

Dermatologists should collaborate with oncologists for management of cutaneous toxicity during BRAF/MEK kinase or immune checkpoint inhibitor therapy because appropriate recognition and control of skin side effects may improve the quality of life of patients with CM and avoid unnecessary interruption of medication. ()
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The frequency of dermatologic assessment for cutaneous toxicity diagnosis and management depends on the agent(s) being used, age of the patient, underlying skin cancer risk factors (eg, history of actinic damage and/or skin cancer), and/ or potential role of skin findings as a biomarker for response. (C)
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Dermatologic assessment every 2-4 wk for the first 3 mo of BRAF inhibitor monotherapy is recommended for patients with numerous squamoproliferative neoplasms, although combination BRAF/MEK inhibition is standard and associated with less skin toxicity. (A)
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Dermatologic assessment of patients undergoing therapy with immune checkpoint inhibitors should occur within the first mo of therapy and continue as needed for management of skin side effects. (A)
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Patients with atopic dermatitis, psoriasis, or other autoimmune dermatoses should be seen before initiation of therapy by a dermatologist for pre-emptive counseling and treatment. ()
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AAD, American Academy of Dermatology; AJCC, American Joint Committee on Cancer; BRAFI, B-Raf proto-oncogene serine/threonine kinase inhibitor; CGH, comparative genomic hybridization; CLND, completion lymph node dissection; CM, cutaneous melanoma; CM, cutaneous melanoma; FISH, fluorescence in situ hybridization; GEP, gene expression profiling; MBAIT, melanocytic BAP1-mutated atypical intradermal tumor; MEKI, mitogen-activated protein kinase inhibitor; MIS LM type, melanoma in situ lentigo maligna type; MMS, Mohs micrographic surgery; NCCN, National Comprehensive Cancer Network; RT, radiation therapy; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy; WE, wide excision

Recommendation Grading

Overview

Title

Management of Primary Cutaneous Melanoma

Authoring Organization

American Academy of Dermatology

Publication Month/Year

November 1, 2018

Last Updated Month/Year

June 9, 2022

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

This guideline addresses the treatment of pediatric, adolescent, and adult patients with American Joint Committee on Cancer (AJCC) clinical stages 0 to IIC primary cutaneous melanoma (CM), including melanomas arising from the nail unit, who may also have histologic evidence of regional nodal disease at presentation via sentinel lymph node biopsy (SLNB), from the perspective of the US dermatologist and other practitioners who treat melanoma.

Target Patient Population

Patients with cutaneous melanoma

Inclusion Criteria

Female, Male, Adolescent, Adult, Child

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management, Treatment

Diseases/Conditions (MeSH)

D008545 - Melanoma, D013518 - Surgery, Plastic, D007167 - Immunotherapy, D005820 - Genetic Testing, D010336 - Pathology

Keywords

biopsy, melanoma, cutaneous melanoma

Methodology

Number of Source Documents
335
Literature Search Start Date
January 1, 2010
Literature Search End Date
April 30, 2017