A young woman comes to the office because her husband has noted that the moles on her back are changing (Figure 168-1). A few have white halos around the brown pigmentation, and some have lost their pigment completely, with a light area remaining. She has no symptoms but wants to make sure these are not skin cancers. Halo nevi are an uncommon variation of common nevi. These appear benign, and the patient is reassured.
A. Multiple halo nevi on the back. B. Close-up of a halo nevus in transition. (Reproduced with permission from Richard P. Usatine, MD.)
Most nevi are benign tumors caused by the aggregation of melanocytic cells in the skin. However, nevi can occur on the conjunctiva, sclera, and other structures of the eye. There are also nonmelanocytic nevi that are produced by other cells, as seen in Becker nevi and comedonal nevi. Although most nevi are acquired, many nevi are present at birth.
Acquired nevi are common lesions, forming during early childhood; few adults have none.
Prevalence appears to be lower in dark-skinned individuals.
Present in 1% to 2% of neonates. In a case series of 594 infants in San Diego, 1.3% had small congenital melanocytic nevi (CMN) and 1% had medium-sized lesions.1 CMNs were most common among African-American (17.9%) and Caucasian (2.6%) infants; none were identified among Hispanic infants.
Prevalence increases through childhood, peaking at puberty; new nevi may continue to appear in adulthood. In a population study of children (N = 180, ages 1 to 15 years) in Barcelona, the mean number of nevi was 17.5.2
Adults typically have 10 to 40 nevi scattered over the body. In a population study in Germany, 60.3% of 2823 adults (mean age: 49 years; 50% women) exhibited 11 to 50 common nevi and 5.2% had at least 1 atypical nevus.3
The peak incidence of melanocytic nevi (MN) is in the fourth to fifth decades of life; the incidence decreases with each successive decade.4
ETIOLOGY AND PATHOPHYSIOLOGY
Benign tumors composed of nevus cells derived from melanocytes, pigment-producing cells that colonize the epidermis.
MN represent proliferations of melanocytes that are in contact with each other, forming small collections of cells known as nests. Genetic mutations present in common nevi as well as in melanomas include BRAF, NRAS, and c-kit.5
Sun (UV) exposure, skin-blistering events (e.g., sunburn), and genetics play a role in the formation of new nevi.4
Nevi commonly darken and/or enlarge during pregnancy. Melanocytes have receptors for estrogens and androgens, and melanogenesis is responsive to these hormones.4
Three broad categories of MN are based on location of nevus cells3:
Junctional nevi—Composed of nevus cells located in the dermal–epidermal junction; may change into compound nevi after childhood (except when located on the palms, soles, or genitalia) (Figure 168-2).
Compound nevi—A nevus in which a portion of nevus cells have migrated into the dermis (Figure 168-3).
Dermal nevi—Composed of nevus cells located within the dermis (usually found only in adults). These are usually raised and have little to no visible hyperpigmentation (Figures 168-4 and 168-5).
Special categories of nevi:
Halo nevus—Compound or dermal nevus that develops a symmetric, sharply demarcated, depigmented border (see Figure 168-1). Most commonly occurs on the trunk and develops during adolescence. Repigmentation may occur.
Blue nevus—A dermal nevus that contains large amounts of pigment so that the brown pigment absorbs the longer wavelengths of light and scatters blue light (Tyndall effect) (Figure 168-6). Blue nevi are not always blue and color varies from tan to blue, black, and gray. Types of blue nevi include amelanotic, desmoplastic, atypical, and malignant variants; genetic mutations seen in blue nevi are often different from those seen in common nevi.5 The nodules are firm because of associated stromal sclerosis. Usually appear in childhood on the extremities, dorsum of the hands, and face. In a case series of blue nevi in older adults (mean age 62.8 years, primarily men), most had been present for less than 10 years and were located on the arm, back, scalp, or face; all were benign.6 A rare variant, the cellular blue nevus is large (>1 cm), frequently located on the buttocks, and may become melanoma. While a typical blue nevus is benign, any variation of typical should be excised, as a nodular melanoma may be masquerading as a blue nevus.
Nevus spilus (speckled nevus)—Hairless, oval, or irregularly shaped brown lesion with darker brown to black dots containing nevus cells (Figure 168-7). May appear at any age or be present at birth; unrelated to sun exposure. Melanoma can arise in a nevus spilus.
Spitz nevus (formerly called benign juvenile melanoma because of its clinical and histologic similarity to melanoma)—A typical benign Spitz nevus may be a hairless, brown, black, red, or reddish-brown dome-shaped papule (Figures 168-8 and 168-9). These are generally found in children but can occur in adults. They can be atypical, and some of these lesions are Spitzoid melanomas. Most importantly, these should be fully excised with clear margins (see Chapter 171, Dysplastic Nevus and Spitz Nevus).
Nevus of Ota—Dark brown nevus that occurs most commonly around the eye and can involve the sclera (Figure 168-10).
Both acquired and CMN hold some risk for the development of melanoma; the number of MN, especially more than 100, is an important independent risk factor for cutaneous melanoma.7 In a 20-year follow-up study of children from families with familial melanoma, the total number of atypical nevi, particularly located on the buttocks, were associated with risk of melanoma.8
Two benign junctional nevi on the arm of a 19-year-old woman. Note how these are flat macules. (Reproduced with permission from Richard P. Usatine, MD.)
Benign compound nevus proven by biopsy on the back of a 35-year-old woman. (Reproduced with permission from Richard P. Usatine, MD.)
Dermal nevus (intradermal melanocytic nevus)—dome shaped with some scattered pigmentation. (Reproduced with permission from Richard P. Usatine, MD.)
Dermal nevus pedunculated with small telangiectasias. (Reproduced with permission from Richard P. Usatine, MD.)
Blue nevus on the left cheek that could resemble a melanoma with its dark color. In this case it was fully excised with a 5-mm punch with a good cosmetic result. Blue nevi are benign and do not need to be excised unless there are suspicious changes. (Reproduced with permission from Richard P. Usatine, MD.)
Nevus spilus on the leg of a young woman from birth. It appears benign and needs no intervention. (Reproduced with permission from Richard P. Usatine, MD.)
Spitz nevus on the nose of an 18-year-old woman. It was biopsied and then excised with no complications. (Reproduced with permission from Richard P. Usatine, MD.)
A. Spitz nevus that grew over the past year on the foot of this 25-year-old man. A 2-mm margin was marked for a saucerization biopsy. B. Dermoscopy with asymmetric streaks and globules indicating growth in the bottom left-hand corner made this suspicious for melanoma. (Reproduced with permission from Richard P. Usatine, MD.)
Nevus of Ota on the face of this young woman since early childhood. It involved both eyes and the skin around both eyes. The scleral pigmentation looks blue. (Reproduced with permission from Richard P. Usatine, MD.)
Becker nevus—A brown patch often with hair located on the shoulder, back, or submammary area, most often in adolescent men (Figures 168-11 and 168-12). The lesion may enlarge to cover an entire shoulder or upper arm. Although it is called a nevus, it does not actually have nevus cells and has no malignant potential. It is a type of hamartoma, an abnormal mixture of cells and tissues normally found in the body where the growth occurs.
Nevus depigmentosus is usually present at birth or starts in early childhood. There is a decreased number of melanosomes within a normal number of melanocytes. It typically has a serrated or jagged edge (Figure 168-13).
Nevus anemicus—A congenital hypopigmented macule or patch that is stable in relative size and distribution. It is due to localized hypersensitivity to catecholamines and not a decrease in melanocytes. On diascopy (pressure with a glass slide) the skin is indistinguishable from the surrounding skin (Figure 168-14).
Nevus comedonicus (comedonal nevus) is a rare congenital hamartoma characterized by an aggregation of comedones in one region of the skin (Figure 168-15).
Epidermal nevi are congenital hamartomas of ectodermal origin classified based on their main component: sebaceous, apocrine, eccrine, follicular, or keratinocytic. See Chapter 169, Congenital Melanocytic Nevi, for a full discussion of this type of nevus.
Becker nevus that developed during adolescence. Hair is frequently seen on this type of nonmelanocytic nevus. (Reproduced with permission from Richard P. Usatine, MD.)
Becker nevus on the back of a 16-year-old Hispanic boy for 2 years. While this nevus did not have hair, it did have increased acne within the area—another feature of the Becker nevus. (Reproduced with permission from Richard P. Usatine, MD.)
Nevus depigmentosus on the face of this young girl since birth. (Reproduced with permission from Richard P. Usatine, MD.)
Nevus anemicus on the posterior neck. The localized hypersensitivity to catecholamines causes the area to stay lighter than the surrounding skin. (Reproduced with permission from Richard P. Usatine, MD.)
Nevus comedonicus on the chest of this 15-year-old boy since birth. This is a congenital hamartoma with open comedones. It is not acne. (Reproduced with permission from Richard P. Usatine, MD.)
Note that nevus comedonicus and epidermal nevi tend to follow Blaschko lines, which come from embryologic development.
In the Barcelona study of children, male gender, history of sunburns, facial freckling, and family history of breast cancer were independent risk factors for having a higher number of nevi.2
In one study among very light-skinned (and not darker skinned) children without red hair, children who develop tans had greater numbers of nevi.9
Most benign MN are skin colored, tan to brown, usually less than 6 mm, with round shape and distinct borders. Nevi in redheads may be pink. The clinical features of the most common acquired MN are:
Junctional nevi—Macular or slightly elevated mole of uniform brown to black pigmentation, smooth surface, and a round or oval border (see Figure 168-2). Most are hairless and vary from 1 to 6 mm.
Compound nevi—Slightly elevated, symmetric, uniformly flesh colored or brown with a round or oval border, often becoming more elevated with age (see Figure 168-3). Hair may be present and a white halo may form.
Dermal nevi (same as intradermal nevi)—Skin color or brown color that may fade with age; dome shaped is most common, but shapes vary, including polypoid, warty, and pedunculated. Often found on the face and may have telangiectasias (see Figures 168-4 and 168-5). Size ranges from 1 to 10 mm.
Most often above the waist on sun-exposed areas, but may appear anywhere on the cutaneous surface; less commonly found on the scalp, breasts, or buttocks.
Among the children in the Barcelona study, 61.1% had nevi on the face and neck, 17.2% on the buttocks, and 11.7% on the scalp; approximately one-third had CMN (Chapter 169, Congenital Melanocytic Nevi).1
In an Australian study of white children, MN of all sizes were highest on the outer forearms, followed by the outer upper arms, neck, and face.10 Boys had higher densities of MN of all sizes on the neck than girls, and girls had higher densities of MN of 2 mm or greater on the lower legs and thighs than boys. Habitually sun-exposed body sites had higher densities of small MN and highest prevalence of larger MN.
Dermoscopy is a useful technique for distinguishing benign nevi from melanoma. For MN, dermoscopic diagnosis relies on color; pattern (i.e., globular, reticular, starburst, and homogeneous blue pattern); pigment distribution (i.e., multifocal, central, eccentric, and uniform); and special sites (e.g., face, acral areas, nail, and mucosa), in conjunction with patient factors (e.g., history, pregnancy).11 (See Chapter 111, Dermoscopy.)
In the Barcelona study, the most frequent dominant dermoscopic pattern was the globular type, with the homogeneous pattern predominating in the youngest children and the reticular pattern predominating in adolescents.1 The reticular pattern is more common in adults as well, but some adults do have a globular pattern if the nevus is still growing. A globular pattern in older adults is suspicious for melanoma, as nevi should not be growing after young adulthood.
There are 10 benign patterns of nevi described in the dermoscopy chapter (see Chapter 111, Dermoscopy). Deviations from these patterns warrant evaluation for melanoma.
A biopsy is needed if a skin lesion is suspicious for melanoma or Spitz nevus (see Chapter 171, Dysplastic Nevus and Spitz Nevus). A biopsy that cuts below the pigmented area is preferred if there is a suspicion for melanoma. This can be done with a saucerization (deep shave), a punch that includes the whole lesion if it is small, or an elliptical excision (see Chapter 113, Biopsy Principles and Techniques). If the patient wants a raised, benign-appearing nevus excised for cosmetic reasons, a shave excision may be adequate. Send all lesions (except skin tags) to the pathologist for examination, even when they appear benign, to avoid missing a melanoma.
Benign nevi may rarely develop into a melanoma. However, most melanomas develop de novo (not from a pre-existing lesion). The skill needed is to distinguish benign lesions such as nevi, seborrheic keratoses, solar lentigines, dermatofibromas, and vascular lesions from melanoma using the naked eye and dermoscopy (when available). The old ABCDE approach (asymmetry, border irregularity, color irregularity, diameter >6 mm, evolution) is a good start but will miss many melanomas if this is relied on as the only method of evaluation. Any lesion that becomes symptomatic (e.g., itchy, painful, irritated, or bleeding), or develops a loss or increase in pigmentation, should be evaluated and biopsied if needed. Dermoscopy is extremely useful to increase one's accuracy in distinguishing among benign nevi, other benign lesions, and melanoma (see Chapter 111, Dermoscopy).
Melanomas are skin cancers that may develop from a preexisting nevus but usually develop de novo. It is critical to know the patterns of all types of melanoma to avoid missing this dangerous skin cancer (see Chapter 179, Melanoma).
Dysplastic nevi (atypical moles) are benign nevi that have a flat component and are larger than 6 mm. Often, the lesions exhibit target-like or fried egg–like morphology, with a central papular zone and a macular surrounding area with differing pigmentation (see Chapter 171, Dysplastic Nevus and Spitz Nevus). If suspicious for melanoma, a saucerization or excision should be performed for pathology. If the pathology is read as severely dysplastic, then the lesion should be managed like a melanoma in situ.
Seborrheic keratoses (SKs) are benign growths that appear more with increasing age and are often hyperpigmented. These are more superficial and stuck-on in their appearance (Chapter 164, Seborrheic Keratosis). Unfortunately, they sometime mimic melanoma and melanoma sometimes appears like an SK, so care should be taken in their evaluation.
Labial melanotic macules are benign dark macules on the lip that are not nevi or melanomas (Figure 168-16). They can be removed for cosmetic purposes or left alone.
Labial melanotic macule. These are benign but are not nevi. (Reproduced with permission from Richard P. Usatine, MD.)
Nevi are generally removed only for cosmetic reasons or because of concern over features of or changes in the lesion that are suggestive of melanoma.
A full excisional biopsy with a sutured closure or a deep shave is usually the best means to diagnose a lesion if concern exists regarding the possibility of melanoma. If the lesion is found to be benign, no further treatment is usually required.
Punch excision can be used to excise smaller lesions.
Deep shave (saucerization)—Unfortunately, if a punch biopsy is used to sample a larger lesion, it may miss a melanoma in another part of the lesion. A broad deep shave is better than a punch biopsy when a full elliptical excision is not possible or desirable (e.g., a large flat pigmented lesion on the face).
Argon laser photoablation has been successfully used for removal of superficial conjunctival nevi in one case series.12
Becker nevi and comedonal nevi do not become melanoma because they lack melanocytes. Therefore, there is no reason to excise them. Generally, these are large, and the risks of excision for cosmetic reasons outweigh the benefits.
Sun protection to limit sunburn may help reduce the appearance of nevi. In a trial of 209 white children, children randomized to the sunscreen group, especially those with freckles, had significantly fewer new nevi on the trunk than did children in the control group at 3-year follow-up.13 Sunscreens can partially prevent ultraviolet-B effects on nevi, but not quite as effectively as physical barriers.14
Degeneration of common nevi into melanoma is very rare. However, in one large Brazilian study, nevus-associated melanomas represented one-third of the identified melanomas; these were associated with intermittent sun exposure, superficial spreading melanomas, and lower Breslow thickness.15
Patients with multiple or large MN appear to have an increased risk of melanoma.4 In a cohort study of patients at high risk for melanoma, of whom 13.6% developed melanoma during 15-year follow-up, just over half were associated with MN; high nevus count was a risk factor.16
Nevi may recur or persist following removal; in one study, dysplastic MN were the most likely to persist.17 In another study, of 61 benign nevi biopsy sites reexamined, two (3.3%) recurred.18
Patients should be encouraged to use sunscreen to prevent skin cancer as well as to reduce the development of new nevi.
Patients with multiple or sizable MN should be taught to look for and report asymmetry, border irregularity, new symptoms, and color and size changes.
SF. A prospective study of cutaneous findings in newborns in the United States: correlation with race, ethnicity, and gestational status using updated classification and nomenclature. J Pediatr
et al. Prevalence study of nevi in children from Barcelona. Dermoscopy, constitutional and environmental factors. Dermatology. 2009;18(3):203–214.
et al. The epidemiology of nevi and signs of skin aging in the adult general population: results of the KORA-Survey 2000. J Invest Dermatol.
PA. Blue nevi and variants: an update. Arch Pathol Lab Med.
SM. Acquired blue nevi in older individuals: retrospective case series from a Veterans Affairs population, 1991 to 2013. JAMA Dermatol
et al. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical nevi. Eur J Cancer.
et al. Acquired melanocytic nevi in childhood and familial melanoma. JAMA Dermatol
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et al. Involution of eruptive melanocytic nevi on combination BRAF and MEK inhibitor therapy. JAMA Dermatol
RP. Site-specific protective effect of broad-spectrum sunscreen on nevus development among white schoolchildren in a randomized trial. J Am Acad Dermatol.
et al. Impact of sunscreens on preventing UVR-induced effects in nevi: in vivo study comparing protection using a physical barrier vs sunscreen. JAMA Dermatol
et al. Nevus-associated melanomas: clinicopathologic features. Am J Clin Pathol
et al. Association of patient risk factors and frequency of nevus-associated cutaneous melanomas. JAMA Dermatol
KF. Persistent melanocytic nevi: a review and analysis of 205 cases. J Cutan Pathol.
D. Low rates of clinical recurrence after biopsy of benign to moderately dysplastic melanocytic nevi. J Am Acad Dermatol.