Меланома

Risk factors for melanoma include

• Sun exposure, particularly repeated blistering sunburns

• Repeated tanning with ultraviolet A (UVA) or psoralen plus UVA (PUVA) treatments

• Nonmelanoma skin cancer

• Family and personal history of melanoma

• Light skin, freckling

• Atypical moles, particularly > 5

• Increased numbers of melanocytic nevi

• Immunosuppression

• Lentigo maligna

• Congenital melanocytic nevus > 20 cm (giant congenital nevi)

• Atypical mole syndrome (dysplastic nevus syndrome)

• Familial atypical mole–melanoma syndrome

• Germline mutations in oncogenes, including BRCA2

• Advanced age

Congenital Melanocytic Nevus

Сховати деталі

Congenital melanocytic nevus (giant congenital nevus) is a risk factor for malignant melanoma. Note the large size (> 20 cm), irregular border, and heterogeneous color.

Photo courtesy of Carl Washington, MD and Mona Saraiya, MD, MPH via the Public Health Image Library of the Centers for Disease Control and Prevention.

Patients with a personal history of melanoma have an increased risk of additional melanomas. People who have one or more first-degree relatives with a history of melanoma have an increased risk (up to 6 or 8 times) over those without a family history.

Atypical mole syndrome is the presence of large numbers of moles (eg,> 50), at least one of which is atypical and at least one of which is > 8 mm in diameter.

Familial atypical mole–melanoma syndrome is the presence of multiple atypical moles and melanoma in 2 or more first-degree relatives; such people are at markedly increased risk (25 times) of melanoma.

Melanoma is less common among people with dark skin; when it occurs in people with dark skin, the nail beds, palms, and soles are more often affected.

Approximately 30% of melanomas develop from pigmented moles (about half each from typical and atypical moles); almost all the rest arise from melanocytes in normal skin. Atypical moles (dysplastic nevi) may be precursors to melanoma.

Although melanomas occur during pregnancy, pregnancy does not increase the likelihood that a mole will become a melanoma; moles frequently change in size and darken uniformly during pregnancy.

The very rare melanomas of childhood almost always arise in the leptomeninges or from giant congenital nevi.

In all people, lesions that have certain characteristics of concern, such as size, irregular borders, recent enlargement, darkening, ulceration, or bleeding, should be evaluated (see diagnosis of melanoma).

Диспластичні невуси (атипові родимки)

Зображення

MID ESSEX HOSPITAL SERVICES NHS TRUST / SCIENCE PHOTO LIBRARY

There are 4 main types of melanoma and a few minor subtypes.

Поверхнево поширена меланома

This type accounts for 70% of melanomas. Typically asymptomatic, it occurs most commonly on women’s legs and men’s torsos.

The lesion is usually a plaque with irregular, raised, indurated, and tan or brown areas, which often have red, white, black, and blue spots or small, sometimes protuberant blue-black nodules. Small notchlike indentations of the margins may be noted, along with enlargement or color change.

Histologically, atypical melanocytes characteristically invade the dermis and epidermis. This type of melanoma most commonly has activating mutations in the BRAF gene at V600.

Поверхнево-поширена меланома

Сховати деталі

This photo shows a superficial spreading melanoma with features of asymmetry, irregular borders, multiple colors, and raised, darker regions with black and blue spots.

Photo courtesy of Gregory L. Wells, MD.

Нодулярна меланома

This type accounts for 15 to 30% of melanomas. It may occur anywhere on the body as a dark, protuberant papule or a plaque that varies from pearl to gray to black. Occasionally, a lesion contains little if any pigment or may look like a vascular tumor.

Unless it ulcerates, nodular melanoma is asymptomatic, but patients usually seek advice because the lesion enlarges rapidly.

Нодулярна меланома

Сховати деталі

The protuberance of this lesion is characteristic of nodular melanoma, which usually appears gray to black.

Photo courtesy of Gregory L. Wells, MD.

Лентиго-меланома

This type accounts for 5% of melanomas. It tends to occur in older adults. It arises from lentigo maligna (Hutchinson freckle or malignant melanoma in situ—a frecklelike tan or brown macule).

Lentigo maligna usually occurs on the face or other areas of chronic sun exposure as an asymptomatic, flat, tan or brown, irregularly shaped macule or patch with darker brown or black spots scattered irregularly on its surface. In lentigo maligna, both normal and malignant melanocytes are confined to the epidermis.

When malignant melanocytes invade the dermis, the lesion is called lentigo maligna melanoma, and the cancer may metastasize.

This type of melanoma most commonly has mutations in the C-kit gene.

Lentigo Maligna Melanoma

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This photo shows lentigo maligna melanoma of the left malar region characterized by multiple macules with irregular borders and heterogeneous color.

Photo courtesy of Carl Washington, MD and Mona Saraiya, MD, MPH, via the Public Health Image Library of the Centers for Disease Control and Prevention.

Лентиго-меланома

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The lesion in this photo is a lentigo maligna melanoma. Characteristic features seen in this lesion are an irregularly shaped flat lesion (macule or patch) and brown or black spots (some darker) that are scattered irregularly.

Photo courtesy of Gregory L. Wells, MD.

Акральна лентигінозна меланома

This type accounts for only 2 to 10% of melanomas. Incidence is probably the same regardless of skin pigmentation, but because people with dark skin infrequently develop other forms of melanoma, acral-lentiginous melanoma is the most common type among them.

Acral-lentiginous melanoma arises on palmar, plantar, and subungual skin and has a characteristic histologic picture similar to that of lentigo maligna melanoma.

This type of melanoma often has mutations in the C-kit gene.

Acral-Lentiginous Melanoma

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This photo shows longitudinal pigmentation of the nail (melanonychia striata; blue arrow) and hyperpigmentation extending across the lunula to the proximal nail fold (Hutchinson sign; red arrow) of the middle finger. Acral-lentiginous melanoma, the most common type of melanoma among people with dark skin, occurs on palmar, plantar, or subungual skin. This patient was diagnosed with acral-lentiginous melanoma (a form of malignant melanoma). (The dark area on the thumbnail is a subungual hematoma.)

Photo courtesy of Carl Washington, MD and Mona Saraiya, MD, MPH, via the Public Health Image Library of the Centers for Disease Control and Prevention.

Акральна лентигінозна меланома

Сховати деталі

This photo shows acral-lentiginous melanoma on the great toe. This melanoma occurs on palmar, plantar, or subungual skin.

Photo courtesy of Gregory L. Wells, MD.

Піднігтьова меланома

Зображення

Photo courtesy of Karen McKoy, MD.

Амеланотична меланома

Amelanotic melanoma is a type of melanoma that does not produce pigment. It can be any of the 4 main types and is most often grouped with the minor categories of melanoma such as spitzoid melanoma, desmoplastic melanoma, neurotropic melanoma, and others.

Accounting for < 10% of melanomas, amelanotic melanomas may be pink, red, or slightly light brown and may have well-defined borders. Their appearance may suggest benign lesions, or a form of nonmelanoma skin cancer, and thereby lead to a late diagnosis and possibly a worse prognosis.

Амеланотична меланома

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This melanoma is amelanotic.

DR P. MARAZZI/SCIENCE PHOTO LIBRARY

• Biopsy

Polarized light and immersion contact dermoscopy may be useful for distinguishing melanomas from benign lesions. However, biopsy and histologic evaluation should be considered if moles have certain characteristics of concern (known as the ABCDEs of melanoma):

• A: Asymmetry—asymmetric appearance

• B: Borders—irregular borders (ie, not round or oval)

• C: Color—color variation within the mole, unusual colors, or a color significantly different or darker than the patient's other moles

• D: Diameter—> 6 mm

• E: Evolution—a new mole in a patient > 30 years of age or a changing mole

Patients at risk can be taught self-examination to detect changes in existing moles and to recognize features suggesting melanoma.

Other red flags include

• Recent enlargement or change in shape

• Change in surface characteristics or consistency

• Signs of inflammation in surrounding skin, with possible bleeding, ulceration, itching, or tenderness

However, recent enlargement, darkening, ulceration, or bleeding usually indicates that the melanoma has already invaded the skin deeply.

If doubt exists, biopsy should include the full depth of the dermis and extend slightly beyond the edges of the lesion. Because earlier diagnosis can be lifesaving and features of melanoma can be variable, even slightly suspect lesions should be biopsied. Earlier diagnosis of melanoma is possible if biopsy specimens can be obtained from lesions having variegated colors (eg, brown or black with shades of red, gray, or blue), irregular elevations that are visible or palpable, and borders with angular indentations or notches.

Biopsy should be excisional for most lesions except those on anatomically sensitive or cosmetically important areas; in these cases, a broad shave biopsy can be done. For broader lesions such as lentigo maligna, representative shave biopsies from several areas can increase the diagnostic yield. By doing step sections, the pathologist can determine the maximal thickness of the melanoma. Definitive radical surgery should not precede histologic diagnosis.

Tumors, particularly if metastatic, are sometimes tested genetically for mutations, eg, to suggest treatment with vemurafenib, a BRAF inhibitor, for metastatic melanomas bearing a V600 mutation in the BRAF gene.

Differential diagnosis includes basal cell carcinomas and squamous cell carcinomas, seborrheic keratoses, atypical moles, blue nevi, dermatofibromas, moles, hematomas (especially on the hands or feet), venous lakes, pyogenic granulomas, and warts with focal thromboses.

• Surgical excision

• Possibly adjuvant radiation therapy, imiquimod, or cryotherapy

• For metastatic or unresectable melanoma, immunotherapy (eg, pembrolizumab, nivolumab, ipilimumab), targeted therapy (eg, vemurafenib, dabrafenib, encorafenib), and radiation therapy

(See also the American Academy of Dermatology Association’s 2019 guidelines of care for the management of primary cutaneous melanoma.)

Treatment of melanoma is primarily by surgical excision (wide local excision). Although the width of margins is debated, most experts agree that a 1-cm lateral tumor-free margin is adequate for lesions < 0.8 mm thick. In tumors < 0.8 mm thick but with ulceration, sentinel lymph node biopsy can be considered. Thicker lesions may deserve larger margins, more radical surgery, and sentinel lymph node biopsy.

Lentigo maligna melanoma and lentigo maligna are usually treated with wide local excision and, if necessary, skin grafting. Intensive radiation therapy is much less effective.

The ideal treatment of melanoma in situ is surgical excision. Sometimes this can be accomplished with staged excisions or Mohs micrographic surgery, in which tissue borders are progressively excised until specimens are tumor-free (as determined by microscopic examination during surgery). If patients decline or are not candidates for surgical therapy (eg, because of comorbidities or involvement of cosmetically important areas), imiquimod and cryotherapy can be considered. Most other treatment methods usually do not penetrate deeply enough into involved follicles, which must be removed.

Spreading or nodular melanomas have usually been treated with wide local excision. Lymph node dissection is recommended when nodes are involved clinically or on histologic evaluation of sentinel lymph node biopsy.

Melanoma may spread rapidly, causing death within months of its recognition, yet the 5-year cure rate of early, very superficial lesions is very high. Thus, cure depends on early diagnosis and early treatment. The 5-year survival rates range from 99.6% for localized melanomas to 73.9% with regional spread and 35.1% with distant metastases (1).

For tumors of cutaneous origin (not central nervous system and subungual melanomas) that have not metastasized, the survival rate varies depending on the thickness of the tumor at the time of diagnosis.

Mucosal melanomas (especially anorectal melanomas) have a poor prognosis, although they often seem quite limited when discovered. They account for a higher proportion of melanomas in Black, Hispanic, and Asian people compared with White people.

Degree of lymphocytic infiltration, which represents reaction by the patient’s immunologic defense system, may correlate with the level of invasion and prognosis. Chances of cure are maximal when lymphocytic infiltration is limited to the most superficial lesions and decrease with deeper levels of tumor cell invasion, ulceration, and vascular or lymphatic invasion.

A commercially available test of gene expression can help determine whether patients who have stage I or II melanomas are at high or low risk of metastases. This test has not yet been added to consensus guidelines; using it to determine whether patients should receive immunotherapy is not recommended at this time.

Because melanoma is associated with ultraviolet (UV) exposure, a number of measures are recommended to limit exposure.

• Sun avoidance: Seeking shade, minimizing outdoor activities between 10 AM and 4 PM (when sun's rays are strongest), and avoiding sunbathing and the use of tanning beds

• Use of protective clothing: Long-sleeved shirts, pants, and broad-brimmed hats

• Use of sunscreen: At least sun protection factor (SPF) 30 with broad-spectrum UVA/UVB protection, used as directed (ie, reapplied every 2 hours and after swimming or sweating); should not be used to prolong sun exposure

However, current evidence is inadequate to determine whether these measures reduce incidence or mortality of melanoma.

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

1. American Cancer Society: Cancer Facts & Figures 2023