Melanoma: Diagnosis and Treatment

Rebecca Lauters; Ashley Dianne Brown; Kari-Claudia Allen Harrington

REBECCA LAUTERS, MD, ASHLEY DIANNE BROWN, MD, MPH, AND KARI-CLAUDIA ALLEN HARRINGTON, MD, MPH

Am Fam Physician. 2024;110(4):367-377

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Cutaneous malignant melanoma accounts for 5% of cancer diagnoses and is the fifth most common cancer diagnosed in the United States. Risk factors for cutaneous malignant melanoma include ultraviolet radiation from sun exposure, Fitzpatrick skin type I or II, a history of dysplastic nevi, indoor tanning, older age, and a personal or family history of melanoma. The U.S. Preventive Services Task Force recommends counseling with patient education on minimizing early ultraviolet radiation exposure, including the use of protective clothing and sunscreen, especially for patients 6 months to 24 years of age. Tools to aid in the diagnosis of cutaneous malignant melanoma and the decision to biopsy include the ABCDE mnemonic, ugly duckling sign, and dermoscopy. Any suspicious pigmented lesion should be biopsied. Biopsy with a deep scoop shave, saucerization, punch biopsy, or full-thickness excision is preferred to ensure the entire lesion is removed to obtain an accurate measurement of Breslow depth. Breslow depth is important in staging, treatment consideration, and prognosis. Wide local excision by a dermatologist or surgeon with appropriate margins is the primary treatment of choice. Thin lesions with a Breslow depth of less than 0.8 mm usually do not need further treatment after wide local excision and have an excellent prognosis. Lesions with a Breslow depth greater than 0.8 mm may need further diagnostic tests or procedures, including sentinel lymph node biopsy, complete lymph node dissection, gene mutation analysis, and possible treatment with systemic immunotherapy. Use of systemic immunotherapies has improved the prognosis for advanced melanoma (stages III and IV), with 5-year survival rates of 74.8% and 35%, respectively, compared with 62.6% and 16% from 1975 to 2011 before immunotherapy was available.

Cutaneous malignant melanoma is the most lethal type of skin cancer accounting for 5% of all cancers and 1% of all skin cancer diagnoses in the United States.^1,2 Malignant transformation of melanocytes, the melanin-producing cells in cutaneous tissue, is the underlying cause of melanoma. Risk factors for cutaneous malignant melanoma include increased exposure to ultraviolet (UV) radiation from indoor tanning and sun exposure and genetic susceptibility (Table 1).²

Clinical recommendation	Evidence rating	Comments
The USPSTF recommends counseling young adults, adolescents, children, and parents about minimizing exposure to UV radiation for people 6 months to 24 years of age with fair skin types to reduce their risk of skin cancer.⁶	B	Large body of evidence and moderate net benefit (USPSTF grade B); shows improved sun protection but limited data on decreased sunburns or melanoma rates
Physicians should consider counseling for adults older than 24 years with fair skin about minimizing their exposure to UV radiation to reduce the risk of skin cancer, but there is insufficient evidence for a visual screening examination in asymptomatic patients without risk factors.^6,7	C	Minimal benefit with minimal risk (USPSTF grade C); insufficient evidence for skin cancer screening (USPSTF grade I)
Dermoscopy, performed by a trained clinician, aids in differentiating melanoma from benign skin lesions during a clinical examination.^16,17	C	Large body of disease-oriented evidence, although evidence in primary care is limited
All suspicious pigmented lesions should be biopsied with an excisional biopsy deep enough to prevent transection of the base of the lesion with 1- to 3-mm circumferential margins excising the entire lesion.^18,19	C	Consensus guidelines

INCIDENCE AND MORTALITY

From 2016 to 2020, the incidence of cutaneous malignant melanoma in the United States was approximately 27 per 100,000 males and 17 per 100,000 females.³ People with Fitzpatrick skin types I and II have the highest incidence of cutaneous malignant melanoma, with 38 and 25 per 100,000 males and females, respectively.³ Fitzpatrick skin types classify skin by the amount of melanin it contains and its reaction to UV radiation exposure, and they are not intended to serve as surrogate markers for race or ethnicity.⁴ Fitzpatrick skin type I is pale, always burns, and does not tan; Fitzpatrick skin type VI is dark, never burns, and always tans darkly. The incidence of cutaneous malignant melanoma in Fitzpatrick skin types V and VI is 1.0 per 100,000, although this population has the highest percentage of late-stage melanomas at the time of diagnosis. This is likely related to differences in presentation, delayed diagnosis, and social factors, which may contribute to increased melanoma mortality in Black patients.⁵ The median age at diagnosis is 65 years for all skin types, although melanoma is one of the most common cancers in women 25 to 34 years of age, with an incidence of about 17 per 100,000 females, which is more than double that of males in that age demographic.^2,3 Despite an increasing incidence of melanoma in the past 10 years, the death rate has decreased 3.5% per year on average in adults.³ Approximately 2.2% of people living in the United States will be diagnosed with melanoma in their lifetime.³

PREVENTION

Recommendations from the U.S. Preventive Services Task Force and American Academy of Family Physicians for parental and patient counseling regarding sun protection against UV radiation include sun avoidance, protective clothing, and sunscreen use in individuals with fair skin to reduce the risk of skin cancer in people 6 months to 24 years of age.⁶ Counseling adults older than 24 years should be considered, specifically in those with an increased risk, although the net benefit is small.⁶ There is insufficient evidence to recommend skin self-examinations for the prevention of skin cancer in adults who are asymptomatic and have no risk factors.⁷ According to the U.S. Preventive Services Task Force, there is insufficient evidence for skin cancer screening with population-based visual inspection in asymptomatic adolescents and adults at low risk.⁷ There is benefit to screening people at increased risk for cutaneous malignant melanoma.

DIAGNOSIS

Most cases of cutaneous malignant melanoma arise de novo, although they also occur in preexisting nevi. Visual inspection is a crucial component of the assessment for suspicious skin lesions.

Clinical Tools

Several visual inspection mnemonics, algorithms, and rules exist to aid in the identification of cutaneous malignant melanoma (Table 2^8–14). There is little evidence to suggest that one tool is superior to another in aiding diagnosis.^8,9 The ABCDE mnemonic, marketed as a self-screening tool for patients, is verified as a clinical tool when used by dermatologists; however, data are lacking for its use in primary care.^8–10 The Glasgow 7-point checklist is used in the United Kingdom for the diagnosis of cutaneous malignant melanoma in primary care.¹⁰ There have been few studies comparing the 7-point checklist to the ABCDE mnemonic, and the results have been mixed regarding diagnostic accuracy.^10,11 The ugly duckling sign (i.e., an outlier mole) is shown to improve detection of cutaneous malignant melanoma when used with other clinical tools by dermatologists.^10,12 Mnemonics can be helpful teaching tools for patients and inexperienced physicians to help identify cutaneous malignant melanoma. Formal education on the detection of cutaneous malignant melanoma in primary care improves physician confidence and knowledge, but studies are lacking on mortality benefit.^10,15

Tool	Criteria	Use
ABCDE (asymmetry, border, color, diameter, evolving) mnemonic	Half of the lesion is different than the other half Irregular or poorly defined border Varied color from one area to another; different shades of tan, brown, black, and sometimes red, white, or blue in the same lesion Larger than 6 mm (pencil eraser) Mole is changing size, shape, or color	Primarily a patient education tool; presence of any one element should prompt evaluation
EFG (elevated, firm, growing) mnemonic: add to ABCDE mnemonic to help identify nodular melanoma	New elevated or thickened lesion Firmness on palpation Lesion grows continuously over 1 month	If any positive findings, consider biopsy
Glasgow 7-point checklist	Change in size of lesion Irregular pigmentation Irregular border Inflammation Itch or altered sensation Larger than other lesions (diameter > 7 mm) Oozing or crusting of lesion	Used by primary care physicians; if three or more elements are present, refer or perform biopsy
Revised 7-point checklist	Major features (2 points each): Change in size of lesion Irregular pigmentation Irregular border Minor features (1 point each): Inflammation Itch or altered sensation Larger than other lesions (> 7 mm diameter) Oozing or crusting of the lesion	Used by primary care physicians to identify clinically significant lesions for biopsy; score of 3 or more warrants a referral or biopsy
Ugly duckling sign	Mole that does not follow the pattern of or look like the surrounding moles on a person's body	Used by patients or physicians to identify possible melanoma

Dermoscopy

Dermoscopy (also known as dermatoscopy or epiluminescence microscopy) is the use of a handheld, lighted magnification tool to evaluate skin lesions (Figure 1¹⁶). Compared with visual inspection alone, dermoscopy performed by a trained clinician increases diagnostic sensitivity for cutaneous malignant melanoma from 76% to 92% and increases specificity from 75% to 95%, with a reduction in the number of missed melanomas of 19 per 1,000 lesions.¹⁷ Dermoscopy is recommended as a diagnostic tool in all clinical practice guidelines for skin cancer. Training in dermoscopy is imperative to success in clinical diagnosis. With training, the use of dermoscopy in primary care can be a useful tool for triaging pigmented lesions.¹⁷ Training on dermoscopy using a formal algorithm is likely to be the most useful for physicians who are not dermatologists. There are insufficient data to recommend any one dermoscopy-based diagnostic algorithm.¹⁷ A previous American Family Physician article has more information on dermoscopy.¹⁶

Biopsy

All suspicious pigmented lesions should be biopsied. Prebiopsy photos are recommended to aid in clinical-pathological correlation and should include regional photographs with anatomic landmarks and dermoscopy images if available.¹⁸ Diagnosis of cutaneous malignant melanoma should be based on a full-thickness excisional biopsy from the deep reticular dermis, with 1- to 3-mm circumferential margins. Deep scoop shave, saucerization, punch biopsy, or fusiform excision techniques are preferred to ensure the entire lesion is removed.^18–21 Superficial shave biopsies or partial (incisional) biopsies are acceptable in some circumstances, such as facial, acral, or very large lesions, although they may underestimate Breslow depth.¹⁸ Breslow depth is the maximal thickness of the primary lesion on pathologic assessment rounded to the nearest 0.1 mm and is one of the most important factors for staging and evaluating the prognosis of cutaneous malignant melanoma.¹⁸ Biopsy of suspicious nail lesions should include the nail matrix and be collected by an experienced physician. For suspicious subungual lesions, enough nail plate should be removed for proper exposure, and an excisional, incisional, or punch biopsy of the nail bed should be performed.¹⁸

TYPES OF MELANOMAS

There are seven types of cutaneous malignant melanoma^21–30 (Figures 2 through 8). Table 3 describes the type and hallmark features.^21–30 The three most common subtypes of cutaneous malignant melanoma are nodular melanoma, superficial spreading, and lentigo maligna.²¹

Type	Hallmark features	Percentage of all melanomas
Melanoma in situ (Figure 2)	Confined to epidermal layer Patient considered cured when treated with surgical removal of 5- to 10-mm margins and pathologic identification of the entire lesion Potential precursor to invasive subtypes of melanoma	Approximately 50
Superficial spreading (Figure 3)	Characterized by slow enlargement of asymptomatic brown or black lesions leading to asymmetrical appearance with irregular borders and pigment variation Commonly occurs on the trunks of males and legs of females but can be found on any part of the body Diameter is typically > 6 mm Most common melanoma in people with fair skin Two-thirds of cases diagnosed between 30 and 50 years of age	67 to 70
Nodular (Figure 4)	Accounts for 37% of fatal cases of cutaneous malignant melanoma Can appear where no lesion was previously present and rapidly penetrate the deeper layers Commonly occurs on the trunk, head, or neck Lesions are firm, raised, and dome-shaped May bleed, itch, and grow rapidly May mimic acne, furuncles, ulcers, or blood blisters Typically, a raised nodule with varying pigment or nonpigmented	15 to 30
Lentigo maligna (Figure 5)	10% to 26% of head and neck melanomas Can be very large lesions, usually larger than 1 cm when diagnosed Common in people older than 65 years Macule that grows into a patch Superficial in situ version of lentigo maligna melanoma Very slow growing on chronically sun-exposed skin over 5 to 15 years	5 to 10
Amelanotic (Figure 6)	5-year survival rate in 2014 was 88% compared with 95% in people with pigmented melanoma Can mimic benign lesions, such as scars or blisters Lesions do not produce melanin; reddish or pink appearance	Less than 5
Subungual (Figure 7)	Extension of discoloration into the skin surrounding the nail (Hutchinson sign) Great toe and thumb account for 90% of cases Greatest percentage of melanoma in Blacks, Asians, and Hispanics Presents as a longitudinal black or brown band of pigmentation on nail Requires nail matrix sampling	0.7 to 3.5
Acral lentiginous (Figure 8)	Appears on palms and soles Biopsy with a narrow excision; partial (incisional) biopsy acceptable in difficult sites Higher prevalence in specific populations: 33% to 36% in Blacks; 18% to 23% in Asian/Pacific Islanders Sample should be taken from the most nodular portion of the lesion for accurate Breslow depth Thought to be less related to ultraviolet radiation exposure and possibly related to shearing forces leading to increased genetic mutations	2 to 3

TREATMENT

Treatment recommendations are based on the stage of melanoma. Surgical removal by a dermatologist or surgeon with wide local excision is the primary treatment modality.¹⁸ Low-risk melanoma (stages 0, IA, IB, and IIA) is often treated with wide local excision alone and usually does not need further treatment and has an excellent prognosis. Treatment for high-risk melanoma (stages IIB, IIC, III, and IV) includes a combination of surgical techniques and medical treatment with systemic therapy. Treatment for high-risk melanoma should be guided by a multidisciplinary team.³¹

Surgical Interventions

Surgical interventions for cutaneous malignant melanoma include wide local excision, sentinel lymph node biopsy, and complete lymph node dissection.

Wide local excision is the removal of the entire lesion with a margin of normal-appearing tissue. Appropriate margins are based on Breslow depth (Table 4).¹⁸ Lesions less than 0.8 mm should undergo excision. If this cannot be performed in the primary care setting, patients should be referred to a dermatologist or surgical specialist. Lesions greater than 0.8 mm should be referred to a surgeon or surgical oncologist for wide local excision and a discussion about the risks and benefits of sentinel lymph node biopsy.^18,32 Wide local excision and sentinel lymph node biopsy should be done simultaneously when possible.³²

Sentinel lymph node biopsy is a procedure that uses a dye that is injected around the lesion to map the nodes that drain the primary lesion; this is typically performed at the same time as wide local excision of the lesion. Sentinel lymph node biopsy is used for staging, clinical trial recommendations, and prognosis discussions.^18–20 It is recommended when the primary tumor has a Breslow depth of 1.1 to 4.0 mm, and the procedure is usually necessary for acceptance into most clinical trials. Sentinel lymph node biopsy is controversial for thin (greater than 0.8 mm to less than 1.0 mm) and very thick (greater than 4.0 mm) melanomas, and patients should have a risk-benefit discussion with the primary surgeon.^33,34

Complete lymph node dissection is a procedure that includes the removal of all the lymph nodes in a group; it does not improve survival in patients with cutaneous malignant melanoma and is associated with significant morbidity. Complete lymph node dissection is no longer recommended as a treatment for cutaneous malignant melanoma after a positive sentinel lymph node biopsy.^35,36

Medical Treatment

Systemic therapies, immunotherapy, and gene targeting therapy are medical treatments for cutaneous malignant melanoma. Immunotherapies increase immune system awareness and response to malignant cells, leading to their destruction. Common genetic mutations of cutaneous malignant melanoma allow cancerous cells to grow and evade the immune system unchecked; targeted therapies, such as BRAF and MEK inhibitors, pinpoint and block these genetic mutations. Although these medications are managed by oncology and dermatology, an awareness of the medications and their adverse effects is necessary for primary care^37,38 (eTable A).

Drug class	Purpose	Type of treatment	Drug	Route of administration	Adverse effects
Immune modulator (monoclonal antibody)	Primes the immune system to recognize melanoma cells	Anti–cytotoxic T-lymphocyte antigen-4	Ipilimumab (Yervoy)	Intravenous	Diarrhea, erythematous maculopapular eruption, fatigue, immune-mediated reactions (dermatitis, endocrine [e.g., adrenal insufficiency, hypophysitis, thyroid dysfunction], enterocolitis, hepatitis, neuropathy), and itching
		Anti–programmed death-1	Pembrolizumab (Keytruda)	Intravenous	Abdominal pain, anemia, arrhythmia, arthralgia, constipation, decreased serum bicarbonate, dyspnea, edema, fatigue, fever, flulike symptoms, headache, hypercalcemia, hyperkalemia, hypertriglyceridemia, increased creatinine, papular eruption, pruritus, transaminitis
			Nivolumab (Opdivo)	Intravenous	Anemia, arthralgia, asthenia, cough, dizziness, dyspnea, edema, fatigue, fever, headache, hypercalcemia, hyperkalemia, hypertension, hyponatremia, leukopenia, lymphocytopenia, neutropenia, pruritus, rash, renal impairment, thyroid dysfunction, vomiting
			Atezolizumab (Tecentriq)	Intravenous	Anemia, asthenia, constipation, decreased appetite, diarrhea, fever, hyperkalemia, hypoalbuminemia, hypomagnesemia, hypothyroid, peripheral neuropathy, rash
Targeted therapy (kinase inhibitor)	Downregulates signals that allow melanoma to proliferate, spread, and evade the immune system	BRAF inhibitor	Vemurafenib (Zelboraf) Dabrafenib (Tafinlar)	Oral	Alopecia, arthralgia, asthenia, constipation, fatigue, fever, hyperkeratosis, nausea, peripheral edema, photosensitivity, QT prolongation, skin erythema, squamous cell skin cancer, vomiting
		MEK inhibitor	Trametinib (Mekinist)	Oral	Acneiform eruption, anemia, dermatitis, diarrhea, edema, hemorrhage, hepatitis, hypertension, hypoalbuminemia, fatigue, lymphedema, lymphopenia, oral ulcers, papulopustular eruptions, photosensitivity
		MEK inhibitor	Cobimetinib (Cotellic)	Oral	Acneiform eruptions, anemia, decreased left ventricular ejection fraction, diarrhea, fever, hemorrhage, hyperkalemia, hypertension, hypoalbuminemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, increased alkaline phosphatase, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased serum creatinine, lymphocytopenia, nausea, rash, retinopathy, stomatitis, thrombocytopenia, transaminitis, vomiting
Cytokine	Boosts the immune system	Stimulates immune system to develop T-cells	Interferon alfa	Intravenous	Aches, blood dyscrasias, chills, fatigue, fevers, flulike symptoms, organ damage, severe anaphylactic reaction
Oncolytic virus	Kills tumor (used in nonresectable melanoma)	Oncolytic virus	Talimogene laher-parepvec (lmlygic)	Intralesional injection	Chills, fatigue, fever, flulike symptoms, injection site pain, nausea
Immune stimulator	Boosts the immune system	Toll-like receptor agonist	Imiquimod (Aldara)	Topical	Local site reactions (e.g., burning, flakiness, itching, redness, scabbing or crusting, swelling of surrounding skin)

Neoadjuvant therapy is treatment that includes systemic or targeted therapy or immunotherapy before surgical intervention for cutaneous malignant melanoma stages III and IV. A few small clinical trials have evaluated the use of the neoadjuvant therapies BRAF and MEK inhibitors and immunotherapies and have shown complete pathologic response in 46% and 43% of participants, respectively, with improved relapse-free survival rates. Neoadjuvant therapy outside of clinical trials is used for tumors that are difficult to resect, when surgery would have high morbidity, and for shrinking the tumor for easier resection.^36–40

Adjuvant therapy involves systemic treatments following wide local excision and sentinel lymph node biopsy. Adjuvant therapy with immunotherapy or gene-targeted therapy is the standard of care for cutaneous malignant melanoma stages IIB through IIC, IIIB through IIID, and IV. Clinical investigations are ongoing for use and clinical benefit in early stages.^18,31,37,40

Use of systemic immunotherapies have improved the prognosis for advanced melanoma (stages III and IV), with 5-year survival rates of 74.8% and 35%, respectively, compared with 62.6% and 16% from 1975 to 2011 before immunotherapy was available.^3,41 Although immunotherapies have revolutionized melanoma treatment, adverse effects are numerous and generally include increased autoimmune effects, such as thyroid dysfunction, colitis, hepatitis, and dermatitis, and dermatologic rashes and eruptions, fevers, fatigue, and flulike symptoms.³⁷

STAGING AND FOLLOW-UP

The stage of disease is determined by the tumor-node-metastasis classification system, which considers the tumor thickness, degree of nodal involvement, and the extent of metastatic spread. Staging information helps determine a treatment plan and should facilitate further discussion, including a follow-up care plan and statistical survival information with 5- and 10-year survival estimates (Table 5).^{3,13,18,19,21,39,42,43} Baseline imaging and laboratory studies are not warranted in the workup or treatment course of asymptomatic cutaneous malignant melanoma stages 0 to IIB, although coordination with oncology is recommended for stages IIB and higher for guidance on imaging.^18,19,21 Imaging and laboratory studies for patients with cutaneous malignant melanoma stages IIC to IV should also be guided by the specialist for evaluation of metastatic disease, staging, and symptomatic patients.^18,21,42,43

Stage	Breslow depth	American Joint Committee on Cancer TNM stage	Overall survival rates at 5 and 10 years	Additional testing for staging	Specific melanoma follow-up and surveillance
0	Melanoma in situ (confined to the top layer of the epidermis)	TisN0M0	99%	—	Examination should focus on local recurrence, and a full skin check should be performed every 3 to 12 months for 1 to 2 years
I	A: < 0.8 mm without ulceration B: < 0.8 mm with ulceration 0.8 to 1.0 mm with or without ulceration > 1.0 to 2.0 mm without ulceration	T1aN0M0 T1bN0M0 T2aN0M0	99%/98% 97%/94%	—	Examination should focus on local recurrence, and a full skin check should be performed every 3 to 12 months for 2 years
II	A: > 1.0 to 2.0 mm with ulceration > 2.0 to 4.0 mm without ulceration B: > 2.0 to 4.0 mm with ulceration > 4.0 mm without ulceration C: > 4.0 mm with ulceration	T2bN0M0 T3aN0M0 T3bN0M0T4aN0M0 T4bN0M0	94%/88% 87%/82% 82%/75%	—	Examination should focus on local recurrence and a full skin check should be performed every 3 to 12 months for 2 years Clinical follow-up is recommended every 3 to 6 months for 2 years, then every 6 to 12 months for 3 years, then annually Collaboration with oncology is recommended for stage IIB and greater for guidance on imaging; imaging is based on risk of recurrence or metastatic disease (not recommended after 3 to 5 years of disease-free follow-up)
III	Any Breslow depth; has spread to nearby lymph nodes or skin Four subgroups based on pathology and nodal disease	Any T, N ≥ 1, M0	IIIA: 93%/88% IIIB: 83%/77% IIIC: 69%/60% IIID: 32%/24%	Laboratory studies, PET, and/or CT determined by treating physician Testing for common genetic mutations (e.g., BRAF)	Clinical follow-up every 3 to 6 months for 2 years, then every 6 to 12 months for 3 years, then annually Laboratory studies as indicated for symptoms of metastatic disease Imaging is based on specialist recommendations (not recommended after 3 to 5 years of disease-free follow-up)
IV	Any Breslow depth; has spread to an internal organ or lymph nodes further from original melanoma	Any T, any N, M1	32%/12%	CBC, complete metabolic profile, LDH level PET and/or CT of the chest, abdomen, or pelvis MRI of the brain Testing for common genetic mutations (e.g., BRAF)	Clinical follow-up every 3 to 6 months for 2 years, then every 6 to 12 months for 3 years, then annually Laboratory studies as indicated for symptoms of metastatic disease Imaging is based on specialist recommendations (not recommended after 3 to 5 years of disease-free follow-up)

FUTURE DIRECTIONS

Cutaneous malignant melanoma is a highly researched area of medicine with many diagnostic and therapeutic technologies being studied. Gene expression profiling uses polymerase chain reaction assays for genetic analysis of pigmented lesions and is an up-and-coming tool that aids in diagnostic precision and risk prediction. Gene expression profiling is not recommended by consensus guidelines because more data are needed regarding the role of its use in clinical decision making, although many dermatologists are already using this technology.⁴⁴ Other newer, noninvasive diagnostic techniques used by dermatologists, including reflectance confocal microscopy, electrical impedance spectroscopy, gene expression analysis, and optical coherence tomography, are out of the scope of this review.^18,44

This article updates previous articles on this topic by Shenenberger²¹; Rager, et al.⁴⁵; Goldstein and Goldstein⁴⁶; and Edman and Wolfe.⁴⁷

Data Sources: A search was completed in PubMed, Essential Evidence Plus, EMBASE, and google scholar using the key terms cutaneous malignant melanoma, incidence, diagnosis, treatment, neoadjuvant, adjuvant, sentinel lymph node biopsy, complete lymph node dissection. The search included meta-analyses, randomized controlled trials, and clinical trials. The Cochrane Database of Systematic Reviews; U.S. Preventive Services Task Force; Surveillance, Epidemiology, and End Results (SEER) Program; National Center for Health Statistics; and the National Cancer Database were also searched. We critically reviewed studies that used patient categories such as race and/or gender but did not define how these categories were assigned, stating their limitations in the text. Search dates: September 27, 2023; April 2024; and July 2024.

The authors thank Dr. Mayeaux for allowing the use of his photos.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Air Force, U.S. Department of Defense, or U.S. government.

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Breslow depth (thickness)	Margins^*
Melanoma in situ	0.5 cm to 1 cm
≤ 1 mm	1 cm
> 1 mm to 2 mm	1 cm to 2 cm
> 2 mm	2 cm