Nevus Cells.

The nevus cell differs from melanocytes. The nevus cell is larger, lacks dendrites, has more abundant cytoplasm, and contains coarse granules. Nevus cells aggregate in groups (nests) or proliferate in a non-nested pattern in the basal region at the dermoepidermal junction. Nevus cells in the dermis are classified into types A (epithelioid), B (lymphocytoid), and C (neuroid). Through a process of maturation and downward migration, type A epidermal nevus cells develop into type B cells and then into type C dermal nevus cells.

Incidence and Evolution.

Moles are so common that they appear on virtually every person. They are present in 1% of newborns and increase in incidence throughout infancy and childhood. The incidence peaks in the fourth to fifth decades. Nevi then diminish in number with advancing age.

Size and pigmentation may increase at puberty and during pregnancy. Nevi may occur anywhere on the cutaneous surface. There is a strong correlation between sun exposure and the number of nevi. Acquired nevi on the buttocks or female breast are unusual.

Nevi Versus Melanoma.

Nevi exist in a variety of characteristic forms that must be recognized to distinguish them from malignant melanoma. Except for certain types, such as large congenital nevi and atypical moles, most nevi have a very low malignant potential.

Nevi vary in size, shape, surface characteristics, and color. The important fact to remember is that each individual nevus tends to remain uniform in color and shape. Although various shades of brown and black may be present in a single lesion, the colors are distributed over the surface in a uniform pattern.

Melanomas consist of malignant pigment cells that grow and extend with little constraint through the epidermis and into the dermis. Such unrestricted growth produces a lesion with a haphazard or disorganized appearance, which varies in shape, color, and surface characteristics. The characteristics of uniformity cannot always be relied on to differentiate benign from malignant lesions because very early melanomas may appear quite uniform, having a round or oval shape with a uniform brown color.

Examination With a Hand Lens and Dermoscope.

Careful inspection of suspicious lesions with a powerful hand lens and dermoscope will reveal a number of features that cannot be appreciated with the naked eye. Dermoscopy is discussed at the end of the chapter.

Classification.

Common moles are subdivided into three types – junction, compound, and dermal – based on the location of the nevus cells in the skin ( Fig. 22.1 ). The three types represent sequential developmental stages in the life history of a mole. During childhood, nevi begin as flat junction nevi in which the nevus cells are located at the dermoepidermal junction. They evolve into compound nevi when some of the cells migrate into the dermis. Migration of all of the nevus cells into the dermis results in a dermal nevus. Dermal nevi usually form only in adults, but this evolution does not consistently occur. Nevi with cells confined to the dermoepidermal junction area tend to be flat, whereas those with cells confined to the dermis are usually elevated.

Developmental stages in the life history of common moles.

Junction Nevi.

Junction nevi are flat (macular) or slightly elevated, and they are light brown to brown-black with uniform pigmentation that may be slightly irregular ( Fig. 22.2 ). The surface is smooth and flat to slightly elevated, and the border is round or oval and symmetric. Most lesions are hairless. Junction nevi vary in size from 0.1 to 0.6 cm; some are larger. Junction nevi may change into compound nevi after childhood, but they remain as junction nevi on palms, soles, and genitalia. Junction nevi are rare at birth and generally develop after the age of 2 years. Degeneration into melanoma is very rare.

Melanocytic nevi. Junction nevus. The lesion is slightly raised, dark, and uniform.

Compound Nevi.

Compound nevi are slightly elevated and skin-colored or brown. They are elevated and smooth or warty and become more elevated with increasing age ( Fig. 22.3 ). They are uniformly round, oval, and symmetric. Hair may be present. If a white halo appears at the periphery of the lesion, it is referred to as a halo nevus.

Melanocytic nevi. Compound nevus. The surface is covered with uniform brown-black dots.

Dermal Nevi.

Dermal nevi are brown or black, but may become lighter or skin-colored with age. Lesions vary in size from a few millimeters to a centimeter. The variety of shapes reflects the evolutionary process in which moles extend downward with age and nevus cells degenerate and become replaced with fat and fibrous tissue.

Dome-shaped lesions are the most common ( Figs. 22.4 to 22.6 ). They generally appear on the face and are symmetric, with a smooth surface. They may be white or translucent, with telangiectatic vessels on the surface mimicking basal cell carcinoma. The structure may be warty ( Fig. 22.7 ) or polypoid ( Fig. 22.8 ). Pedunculated lesions with a narrow stalk are located on the trunk, neck, axillae, and groin. They may appear as a soft, flabby, wrinkled sack ( Fig. 22.9 ). Solitary cutaneous mucinosis, spiradenoma, eccrine poroma, and palisaded encapsulated neuroma can mimic dermal nevi ( Figs. 22.10 to 22.13 ).

Melanocytic nevi. Dermal nevus. Skin-colored with surface vessels; resembles basal cell carcinoma.

Melanocytic nevi. Dermal nevus. Dome shaped.

Melanocytic nevi. Dermal nevus. Skin-colored and dome shaped.

Melanocytic nevi. Dermal nevus. Warty (verrucous) surface.

Melanocytic nevi. Dermal nevus. Polypoid.

Melanocytic nevi. Dermal nevus. Pedunculated with a soft, flabby, wrinkled surface.

Eccrine poroma. A–B, A benign dome-shaped papule on the plantar aspect of the foot. They may be seen on the palms as well.

Palisaded encapsulated neuroma. Skin-colored to lightly tan dome-shaped papule. This papule is similar to a dermal nevus and a basal cell carcinoma. When this papule is biopsied by shave biopsy, the neuroma tissue often protrudes up out of the wound like a jack-in-the-box.

Solitary cutaneous mucinosis. A–B, A benign, clear, dome-shaped firm papule containing mucin. Multiple cutaneous mucin deposits may be associated with systemic disease.

Spiradenoma. A benign clear to light pink dome-shaped papule. Histologically there was overlap with a cylindroma, another eccrine-derived growth. They may appear similar to dermal nevi.

Elevated nevi are exposed and are prone to trauma from clothing and other stimuli, often causing them to bleed and inflame, making some patients suspect malignancy. A white border may appear, creating a halo nevus. Degeneration to melanoma is very rare, but dermal nevi may resemble nodular melanoma (NM); therefore knowledge of duration and a history of recent change is important.

Suspicious Lesions.

Any pigmented lesion suspected of being malignant should be biopsied or referred for a second opinion. Suspicious lesions should be completely removed by excisional biopsy down to and including subcutaneous tissue.

Nevi.

Patients frequently request removal of nevi for cosmetic purposes. It is good practice to biopsy all pigmented lesions; therefore total removal by electrocautery should be avoided. Nevi are removed either by shave excision or by simple excision and closure with sutures. Most common nevi are small and shave excision is adequate.

Recurrent Previously Excised Nevi (Pseudomelanoma).

Weeks to months after incomplete removal of a nevus, brown macular pigmentation may appear in the scar ( Fig. 22.14 ). Some nevus cells remain with shave excision and partial repigmentation is possible. Residual pigmentation may be removed with electrocautery or cryosurgery. An unusual histologic picture resembling melanoma (pseudomelanoma) may follow partial removal of nevi. If the repigmented area is excised, the pathologist should be notified that the submitted tissue was acquired from a previously treated area. Histologically, the melanocytes appear atypical but are confined to the epidermis, and there is no lateral spread of individual melanocytes as is seen in melanoma.

Recurrent, previously excised nevi (pseudomelanoma). Brown, macular pigmentation may appear in the scar of an incompletely removed nevus.

Nevi With Small Dark Spots.

A small percentage of small dark spots within melanocytic nevi (MNs) are due to melanoma. These roundish areas of brown or black hyperpigmentation measure 3 mm or less in diameter and are located peripherally. Biopsy specimens of nevi with small dark dots should be sectioned to ensure histologic examination of this focus of hyperpigmentation.

Congenital Melanocytic Nevi.

It is estimated that between 1% and 6% of the population have a congenital melanocytic nevus (CMN). Congenital melanocytic nevi (birthmarks) are present at birth and vary in size from a few millimeters to several centimeters, covering wide areas of the trunk, extremity, or face. Some lesions first become apparent during infancy. Not all pigmented lesions present at birth are CMNs; café-au-lait macules and neurofibromas may also be present at birth. Congenital nevi may contain hair; if present, it is usually coarse. Such nevi are uniformly pigmented, with various shades of brown or black predominating, but red or pink may be a minor or sometimes predominant color. Most are flat at birth but become thicker during childhood, and the surface becomes verrucous and sometimes nodular. Scalp CMN may lighten with time. Table 22.1 summarizes clinical considerations for CMN.

Classification.

The diameter of CMNs serves as the major criterion for determining risks of adverse outcomes such as melanoma. Other factors such as diameter, satellite nevus count, anatomic localization, color heterogeneity, surface rugosity, hypertrichosis, and dermal or subcutaneous nodules should be considered when examining CMNs.

Small Congenital Melanocytic Nevi.

The incidence of malignant degeneration in small congenital nevi (<1.5 cm in diameter) is extremely low and prophylactic removal is not recommended ( Fig. 22.15 ). Melanomas arising within a small CMN occur superficially and may be detected visually at an early stage. In most cases, prophylactic excision is performed after puberty, since melanoma does not tend to occur within the early childhood years. Multiple factors must be considered in the management of small CMN (see Table 22.1 ).

A small congenital nevus has a uniform cobblestone surface and may be covered with hair.

Medium-Sized Congenital Melanocytic Nevi.

The risk of the occurrence of malignant melanoma in medium-sized (1.5 to 19.9 cm in diameter) CMN is the subject of controversy ( Figs. 22.16 and 22.17 ). Management is determined on a case-by-case basis. Banal-appearing medium-sized CMN may be observed for changes and should not be prophylactically removed. Individual medium-sized CMN should be monitored for change with photographs. Changing or suspicious areas within the nevus should be biopsied or the entire CMN should be surgically removed (see Table 22.1 ).

Medium-sized congenital nevus. Pigmentation is variable and nonuniform, but a biopsy showed all such areas were benign.

Medium-sized congenital nevus. The border is irregular and appears notched, but that characteristic is maintained in a uniform manner around the entire border.

Large Congenital Melanocytic Nevi (LCMN).

LCMN may undergo malignant transformation (see Table 22.1 ; Figs. 22.18 and 22.19 ). The incidence ranges from 1.8% to 7.1%. Approximately half of the melanomas occur by 3 to 5 years of age. Many of the melanomas arise within the deeper tissues and therefore are detected at advanced stages. Melanoma occurs less often in the head and neck location and has not been detected within satellite nevi. Management of large CMN requires a multidisciplinary approach to care (see Table 22.1 ).

Large congenital hairy nevus.

Giant congenital nevus (bathing trunk nevus).

Dermoscopy of Congenital Melanocytic Nevi.

The most commonly observed dermoscopic features are globules (79.7%), reticular networks (70.3%), hypertrichosis (68.9%), milia-like cysts (52.7%), and perifollicular hypopigmentation (32.4%).

Neurocutaneous Melanosis (NCM).

Proliferation of melanocytes in the leptomeninges and CNS may occur in patients with CMN. Patients at greatest risk for NCM are those with large CMN >40 cm, multiple satellite nevi, and more than two medium-sized CMN. MRI with gadolinium is the best test to detect NCM (see Table 22.1 ). The median age of presentation is 2 years of age. Patients may have developmental disabilities and seizures. Death occurs in up to 34% of patients with symptomatic NCM. Patients with NCM must be followed closely by a neurologist and have serial MRI examinations (see Table 22.1 ).

Management of Congenital Melanocytic Nevi.

Risk assessment and treatment options are considered for each patient. Medical and psychosocial concerns need to be discussed. Management goals are to decrease the risk for developing melanoma by surgical removal and to produce good cosmetic results. Removal of a small CMN, with a low risk for developing melanoma, may result in a disfiguring scar and would not be acceptable. Removal of a large, thick CMN that leaves a large, dense scar may be acceptable. Timing of surgery is a consideration. The best surgical scars result from surgery performed early in life; however, it may be best to delay surgery until after age 2 when the full extent of the nevus is evident. Very large lesions may require multiple procedures. CMNs should be removed down to the fascial layer.

Prophylactic Treatment.

Prophylactic removal is considered for thick lesions in which it is difficult to detect melanoma. Dense nevi with a wrinkled (rugous) surface have the greatest risk. Growths that appear in covered areas (e.g., scalp, medial buttocks, perianal, genital areas) that are difficult to examine and follow are considered for early excision.

Speckled Lentiginous Nevus.

Speckled lentiginous nevus (nevus spilus) is a common hairless, oval or irregularly shaped brown lesion that is dotted with darker brown-to-black spots. They may appear at any age. Lesions can appear at birth or in early infancy as lightly colored café-au-lait macules. Pigmented macules and papules then develop over a period of months to years. Lesions may be very large. It has been suggested that speckled lentiginous nevus is a subtype of CMN. The brown area is usually flat, and the black dots may be slightly elevated and contain typical nevus cells ( Fig. 22.20 ). The spots range from 1 to 3 mm in diameter and may be lentigines, junctional, compound, or intradermal nevi. The background hyperpigmentation histologically has the features of a lentigo or café-au-lait macule. There is considerable variation in size, ranging from 1 to 20 cm. The anatomic position or time of onset is not related to sun exposure. Transformation into melanoma is rare. The risk of transformation may be similar to that for classic congenital nevi of similar size. Examine lesions periodically and educate the patient regarding the clinical signs of melanoma. Routine excision is not necessary. Biopsy suspicious areas. Speckled lentiginous nevus is flat and necessitates excision and closure if the patient desires removal. Lasers have been used to treat both the background hyperpigmentation and the speckles of speckled lentiginous nevi.

Speckled lentiginous nevus. A, A large, brown, macular lesion resembling a café-au-lait macule. Tiny black papules are uniformly distributed over the surface. B, The macular pigmentation is less prominent than in the lesion illustrated in ( A ). C, The macular pigmentation is almost entirely absent. The multiple papules containing nevus cells predominate. D, Macular pigmentation is variable.

Becker Nevus.

Becker nevus is not a nevocellular nevus because it lacks nevus cells. The lesion is a developmental anomaly consisting of either a brown macule ( Fig. 22.21 ) or a patch of hair ( Fig. 22.22 ), or both ( Fig. 22.23 ). Nonhairy lesions may later develop hair. The lesions appear in adolescent men on the shoulder, submammary area, and upper and lower back; they rarely appear on the lower limbs. Becker nevus varies in size and may enlarge to cover the entire upper arm or shoulder. The border is irregular and sharply demarcated.

Becker nevus. This irregular lesion contains no hair. It has been stable in size for years.

Becker nevus. This lesion contains no pigmentation.

Becker nevus. A typical lesion with macular pigmentation and hair.

Becker nevus syndrome is the presence of an epithelial nevus showing hyperpigmentation, increased hairiness, and hamartomatous augmentation of smooth muscle fibers as well as other developmental defects such as ipsilateral hypoplasia of the breast and skeletal anomalies, including scoliosis, spina bifida occulta, or ipsilateral hypoplasia of a limb. The Becker nevus syndrome usually occurs sporadically.

Dermoscopic features of Becker nevus include network, focal hypopigmentation, skin furrow hypopigmentation, hair follicles, perifollicular hypopigmentation, and vessels.

Becker nevus is usually too large to remove by excision. The hair may be shaved or permanently removed. Laser removal of hair and pigmentation is reported.

Halo Nevi.

A compound or dermal nevus that develops a white border is called a halo nevus. The incidence in the population is estimated to be 1%. Halo nevi are found most commonly in children. The average age of onset is 15 years. Halo nevi typically persist for a decade or longer. The depigmented halo is symmetric and round or oval with a sharply demarcated border ( Fig. 22.24 ). There are no melanocytes in the halo area. Halo nevi have the dermoscopic features of benign MNs, with globular and/or homogeneous patterns that are typically observed in children and young adults. Halo nevi structural patterns remain unchanged over time. Patients with Turner syndrome (short stature, gonadal dysgenesis, webbed neck, cubitus valgus, and lymphedema at birth) have a halo nevus prevalence of 18%.

Halo nevi. A–E , An inflammatory infiltrate develops in a nevus and results in a zone of depigmentation surrounding the nevus. As in vitiligo, melanocytes in the epidermis are absent. Halo nevi are found most commonly in children. The average age is 15 years. Halo nevi may be multiple and are seen most frequently on the trunk.

Histologic Characteristics.

T lymphocytes at the site of depigmentation suggest that these cells participate in the halo phenomenon. Most halo nevi are located on the trunk; they never occur on palms and soles. They may occur as an isolated phenomenon, or several nevi may spontaneously develop halos. Halos may repigment with time, or the nevus may disappear. Repigmentation often takes place over months or years; however, it does not always occur. Repigmentation does not follow removal of the nevus. The incidence of vitiligo may be increased in patients with halo nevi. A halo may rarely develop around malignant melanoma, but in such instances it is usually not symmetric.

Removal of a halo nevus is unnecessary unless the nevus has atypical features. Parental concern over this impressive change is often the reason for a conservative excision. In such cases, the mole part of a halo nevus may be removed by shave, excision, or laser.

Spitz Nevus.

Spitz nevus (Spitz tumor, spindle and epithelioid cell nevus) is most common in children but does appear in adults. The most frequent sites include the head and neck regions (37%) and lower extremities (28%). They are hairless, red or reddish-brown, dome-shaped papules or nodules with a smooth ( Fig. 22.25 ) or warty surface; they vary in size from 0.3 to 1.5 cm. The color is caused by increased vascularity, and bleeding sometimes follows trauma. Spitz nevi are usually solitary but may be multiple. They appear suddenly and, contrary to slowly evolving common moles, patients can sometimes date their onset. Banal-appearing, stable Spitz nevi may be monitored clinically. Atypical Spitz nevi (growing, bleeding, change in color, unusual dermoscopic findings) should be completely removed for microscopic examination. Histologic differentiation from melanoma is sometimes difficult. Histopathologic features that suggest more aggressiveness relate to mitotic activity, mitoses near the base, and inflammation.

Spitz nevus. A–B , A reddish, dome-shaped nodule that generally appears in children.

Dermoscopy of Spitz nevus shows: (1) a starburst pattern, characterized by a prominent, black to blue diffuse pigmentation and pseudopods regularly distributed at the periphery in a radiate pattern; and (2) a globular pattern, typified by a discrete, brown to gray-blue pigmentation and a peripheral rim of large brown globules, often extending throughout the entire lesion.

Blue Nevus.

The blue nevus is a slightly elevated, round, regular nevus, usually less than 0.5 cm, and contains large amounts of pigment located in the dermis ( Figs. 22.26 to 22.28 ). The brown pigment absorbs the longer wavelengths of light and scatters blue light (Tyndall effect). The blue nevus appears in childhood and is most common on the extremities and dorsum of the hands. A rare variant, the cellular blue nevus, is larger (usually greater than 1 cm) and nodular and is frequently located on the buttocks.

Blue nevus. Most lesions are small and round.

Blue nevus. Black papule with a rim of erythema.

Blue nevus. Dark blue to black papule on the scalp. The papule had been unchanged for years.

Melanomas are reported as arising in association with a common or cellular blue nevus and arising de novo and resembling cellular blue nevi. Blue nevi may be removed for cosmetic purposes.

Dermal Melanocytosis.

Deep blue-black pigmentation due to melanocytes in the dermis may be seen in newborns with darker skin types. It is an isolated cutaneous finding and usually resolves by the toddler years ( Fig. 22.29 ). Dermal melanocytosis may be confused with child abuse and rarely is associated with inborn errors of metabolism.

Congenital dermal melanocytosis. A diffuse pigmentation in a normal child. When widespread, dermal melanocytosis may be associated with lysosomal storage disease. Dermal melanocytosis on the sacral and buttock areas has been mistaken for child abuse.

Labial Melanotic Macule.

Brown macules on the lower lip are relatively common, especially in young adult women ( Fig. 22.30 ). Histologically, they resemble freckles and not lentigo, but unlike freckles, they do not darken with sun exposure. They are benign. Cryotherapy or laser surgery is used for patients who request treatment.

A–B, Labial melanotic macule. These common lesions worry the patient who suspects melanoma. They are benign.

Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM).

The FAMMM syndrome is an autosomal-dominantly inherited condition seen in patients with the following criteria:

• 1.
  

  The occurrence of malignant melanoma in one or more first- or second-degree relatives

  
  
• 2.
  

  The presence of a large number of MNs, often more than 50, some of which are atypical and often variable in size.

  
  
• 3.
  

  The development of MNs that demonstrate certain histologic features.

Atypical Melanocytic Nevi Association With Melanoma.

Individuals with atypical nevi have up to a 20-fold increased risk of developing malignant melanoma, compared to those without atypical nevi. The risk for melanoma increases as the number of atypical nevi increases. Seventy percent of melanoma arises de novo and is not associated with a precursor melanocytic nevus. For this reason, prophylactic removal of atypical nevi is not recommended. Individuals with multiple atypical nevi and a family history of melanoma have a 15% risk of developing melanoma. Individuals who have multiple atypical nevi and a personal history of melanoma have a 10% risk of developing a second melanoma. The lifetime risk of melanoma approaches 100% for those individuals with multiple atypical nevi and two or more first-degree relatives with melanoma.

Morphology.

These unusual nevi differ in a number of important ways from typical acquired pigmented nevi or moles (see Table 22.2 ). AMs are larger than common moles. They have a mixture of colors, including tan, brown, pink, and black. The border is irregular and indistinct and often fades into the surrounding skin. The surface is complex and variable, with both macular and papular components ( Fig. 22.31 ). A characteristic presentation is a pigmented papule surrounded by a macular collar of pigmentation (“fried-egg lesion”) ( Fig. 22.32 ). In one study, the total number of nevi and macular components were the only useful features to predict histologic melanocytic dysplasia. However, “fried-egg lesions” often do not display histologic melanocytic dysplasia. In contrast, the absence of a macular component in MNs in a person with fewer than 13 total body nevi accurately predicts the absence of melanocytic dysplasia on histologic examination.

Atypical nevi. There are numerous large nevi present. A black nodular melanoma is present on the mid-lower back.

Atypical nevi. A, Macular brown pigmentation with uniform dots. B, Brown pigmentation with a complex pattern. C, Clinical differentiation from melanoma is difficult. D, Uniform, brown homogeneous pigmentation. E, “Fried-egg lesion.” The papular component is dark and uniformly pigmented. F, “Fried-egg lesion.” The macular and papular components are uniformly pigmented.

Surface Characteristics.

The surface characteristics of atypical nevi are distinctive and can be appreciated with a hand lens and dermoscope.

Development and Distribution.

Atypical moles are not present at birth, but begin to appear in the mid-childhood years as typical common moles. The appearance changes at puberty, and newer lesions continue to appear well after the age of 40. Common moles occur most often on sun-exposed areas. AMs occur in those locations and at unusual sites such as the scalp, buttocks, and breast. The predilection sites for melanoma in familial AM patients of both genders correspond with the distribution of nevi; in males, nevi and melanoma counts are higher on the back; in females, both the back and the lower extremities are affected. These findings strongly suggest an association between nevus distribution and melanoma occurrence and site in familial AMs.

Histologic Characteristics.

The National Institutes of Health (NIH) Consensus Conference listed the histologic criteria as follows: architectural disorder with asymmetry, subepidermal (concentric eosinophilic and/or lamellar) fibroplasia, and lentiginous melanocytic hyperplasia with spindle or epithelioid melanocytes aggregating in nests of variable size and forming bridges between adjacent rete ridges. Melanocytic atypia may be present to a variable degree. In addition, there may be dermal infiltration with lymphocytes, as well as the “shoulder” phenomenon (intraepidermal melanocytes extending singly or in nests beyond the main dermal component).

Management.

Management recommendations are given in Box 22.1 .

Surgical Excision and Re-Excision.

Consensus guidelines were developed for surgical and reexcision of atypical nevi ( Box 22.2 ).

Epidemiology.

In the United States, melanoma is the fifth most common cancer after prostate, lung, colon, and bladder in men and breast, colon, uterine, and thyroid in women. In 2018, the National Cancer Institute estimated 91,270 new cases and 9320 deaths in the United States. The incidence of melanoma has continued to increase since 1992, but the number of deaths has not substantially decreased. Fig. 22.33 summarizes the current survival curves. The risk of developing melanoma is 20 times higher for whites (1 in 38) than Hispanics (1 in 172) and African Americans (1 in 1000). The risk for melanoma increases with age (average age at diagnosis 63), but melanoma is one of the most common cancers in young adults (age 20 to 39), especially women. The arms and legs are common sites in women and the back and shoulders in men. In nonwhites, the lower extremities and acral sites are most commonly affected.

Comparison of survival curves in four stages of melanoma. Based upon 2009 AJCC melanoma TNM classification and prior to advent of targeted therapy or immunotherapy.

(Redrawn from Balch CM. Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al. (eds). AJCC Cancer Staging Manual, 7th ed. New York: Springer Verlag, 2009.)

Risk for Melanoma.

The risk factors for melanoma are listed in Table 22.3 .

TABLE 22.3

Risk Factors for Development of Single or Multiple Primary Melanomas *

Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cutaneous Melanoma V.3.2019. © 2019 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Male sex

Age >60 years

Phenotypic predisposition

• Atypical mole/dysplastic nevus pattern

• Increased mole count (particularly large nevi)

• Sun-phenotype/tendency to sunburn

• Red hair, blue eyes/Fitzpatrick skin type I/phenomelanin predominant phenotype

Personal medical history/comorbidities

• Multiple and/or blistering sunburns

• Precancer/cancers, especially:

• Actinic keratosis/nonmelanoma (keratinocyte) skin cancer (e.g., basal cell and squamous cell carcinomas)

• Childhood cancer

• Immunosuppression/immune perturbation related to:

• Solid organ transplantation

• Hematopoietic cell transportation

• Human immunodeficiency virus/acquired immunodeficiency syndrome

• Rare genodermatoses

• Xeroderma pigmentosum

Genetic predisposition

• Presence of germline mutations or polymorphisms predisposing to melanoma (including CDKN2a , CDK4 , MC1R , BAP1 , and potentially other genes).

• Family history of cutaneous melanoma (especially if multiple), pancreatic cancer, astrocytoma, uveal melanoma, and/or mesothelioma.

Environmental factors

• Tanning bed use

• Residence in sunnier climate/latitude nearer equator

• Intermittent, intense sun exposure (for truncal/extremity melanomas, often observed with associated increased nevus count)

• Chronic sun exposure (for head/neck/arm melanomas, often associated with lower nevus count)

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