INTRODUCTION — Acquired melanocytic nevi will be discussed here. Congenital melanocytic nevi and other benign pigmented lesions are discussed separately. (See "Congenital melanocytic nevi" and "Benign pigmented skin lesions other than melanocytic nevi (moles)".)
OVERVIEW — Melanocytic nevi are benign proliferations of a type of melanocyte known as a "nevus cell." The two major differences between ordinary melanocytes that reside in the basal layer of the epidermis and nevus cells are:
●Nevus cells cluster as nests within the lower epidermis and/or dermis, whereas epidermal melanocytes are evenly dispersed as single units.
●Nevus cells do not have dendritic processes, except for those within blue nevi.
Both melanocytes and nevus cells can produce the pigment melanin. Melanocytic nevi may be congenital or acquired. Acquired nevi can be classified as common (banal) or atypical, and there are several additional variants, including halo nevi, blue nevi, and Spitz nevi.
Terminology — The names applied to acquired nevi reflect the location of the nests of melanocytes (figure 1). In junctional nevi, the nests of melanocytes are at the dermal-epidermal junction. In compound nevi, the nests of melanocytes are at the dermal-epidermal junction and in the dermis. In intradermal nevi, the nests of melanocytes are in the dermis. With progressive migration of melanocytes from the dermal-epidermal junction into the dermis, nevi become more elevated and less pigmented.
Predisposing factors — Factors related to the development of nevi (with the exception of blue and perhaps Spitz nevi) include:
●Heredity, with a familial tendency to have a large number of moles. Germline polymorphisms that impact the number, morphology (eg, raised versus flat), and dermoscopic features (eg, globular versus reticular pattern) of nevi have been identified in several genes, including interferon regulatory factor 4 (IRF4) and telomerase reverse transcriptase (TERT) [1].
●Degree of sun exposure during childhood, especially when intense and intermittent [2-7]. Although the results of studies evaluating the effects of sunscreen use on the development of nevi are inconsistent, in one randomized controlled study, school-aged children who were supplied with and instructed to use a broad-spectrum sunscreen developed significantly fewer new nevi over a three-year period than controls [8,9]. Secondary environmental factors that influence development and growth of acquired melanocytic nevi in children include blistering disorders, lichen sclerosus, chemotherapy, systemic immunosuppression, and endocrine conditions [10].
●Phenotypic characteristics such as skin type, with higher nevus counts seen in individuals with lightly pigmented skin [3,7,11-13]. The mean number of nevi in White adolescents is approximately 15 to 30, compared with five or fewer in Black, Asian, or Native American adolescents [11,13]. However, individuals with the fairest skin, especially when accompanied by red hair, also tend to have fewer nevi than children with dark hair [14,15].
Diagnosis — The diagnosis of a nevus is based upon the clinical appearance, as described below.
Melanocytic nevi with atypical features must be differentiated from melanoma. Clinical characteristics suggestive of melanoma include diameter >6 mm, irregular borders, asymmetry, variable pigmentation, and change in appearance of a longstanding pigmented lesion. (See 'Atypical nevi' below and "Screening for melanoma in adults and adolescents" and 'Biopsy considerations' below.)
COMMON ACQUIRED MELANOCYTIC NEVI
Clinical features
General features — Common (banal) nevi have a wide variety of clinical appearances. However, they tend to be ≤6 mm in diameter and symmetric with a homogeneous surface, even pigmentation, round or oval shape, regular outline, and sharply demarcated border (picture 1). Close inspection sometimes reveals pigmentary stippling or perifollicular hypopigmentation. Nevi are often concentrated in sun-exposed areas of the trunk or, particularly in girls, on the lower extremities [16]. Less commonly, they occur in acral sites such as the palms, soles, and nail matrix. As many as one-third of children and adolescents have acquired nevi on the scalp, and nevi in this location may be a marker for the development of a greater total number of nevi [17].
Nevi on palms/soles — Nevi on the palms and soles (acral melanocytic nevi) occur in individuals of all ethnic backgrounds, but are more common in those with dark skin pigmentation or numerous melanocytic nevi [18-21]. Nevi located on the palms and soles are usually of the junctional or compound type, and are typically brown to dark brown in color. They often have linear streaks of darker pigmentation that reflect the prominent skin markings in these sites. (See "Dermoscopy of pigmented lesions of the palms and soles".)
Referral to a dermatologist is generally warranted when acquired acral nevi have marked asymmetry, mottled pigmentation, or a large size (≥6 mm). (See "Pathologic characteristics of melanoma", section on 'Acral lentiginous melanoma'.)
Nevi originating from the nail matrix — Acral nevi or lentigines that involve the nail matrix can present as longitudinal melanonychia, a tan, brown, or black streak caused by increased melanin deposition in the nail plate (picture 2). In darkly pigmented individuals, longitudinal melanonychia is commonly seen on multiple nails due to increased melanin production by normal nail matrix melanocytes (picture 3). Streaks that develop in childhood are usually benign [22]. However, single bands that are dark/irregular in color or wide (≥4 mm), become darker or wider with time, are associated with nail dystrophy, or have extension of pigmentation beyond the nail fold may warrant biopsy of the nail matrix to exclude melanoma [23]. (See "Overview of nail disorders", section on 'Longitudinal melanonychia' and 'Biopsy considerations' below.)
Natural history — Common acquired melanocytic nevi begin to appear after the first six months of life, increase in number during childhood and adolescence, reach a peak count in the third decade, and then slowly regress with age [11,24]. Substantial nevus turnover also occurs during the first two decades of life. For example, over a three- to four-year period in early adolescence, the net number of nevi increases by a mean of 40 to 60 percent and approximately 15 percent of nevi disappear [24,25]. Although a changing nevus may raise concern for melanoma in an adult, enlargement and increased elevation occur as part of the normal natural history of nevi in children and adolescents [26].
The clinical and histologic evolution of individual lesions from junctional to compound to dermal nevi (figure 1) can correspond to this cycle:
●Junctional nevi – Junctional nevi are macular or minimally raised, have preserved skin markings, and range from brown to black in color, sometimes with darker pigmentation in the center than at the edge (picture 4). They can be similar in appearance to simple lentigines. (See "Benign pigmented skin lesions other than melanocytic nevi (moles)", section on 'Simple lentigo'.)
●Compound nevi – Compound nevi are classically pigmented papules, but in some lesions the degree of elevation is subtle. Their surface can be smooth and dome-shaped or papillomatous, and they vary in color from tan to dark brown (picture 5). The more symmetric and uniform in color a compound nevus is, especially when tan to medium brown in color, the less one needs to worry about the lesion
●Intradermal nevi – Nevus cells residing in the dermis often lose their capacity to produce melanin. As a result, intradermal nevi are usually skin-colored to tan papules that are dome-shaped, papillomatous, or pedunculated with a soft, rubbery texture (picture 6). Occasionally, they have speckles of brown pigmentation, terminal hairs, or pseudo-horn cysts (ie, accumulations of keratin within invaginations of hyperplastic epidermis). Pseudo-horn cysts occur more frequently in seborrheic keratoses, which typically develop in adults, than in intradermal nevi. (See "Overview of benign lesions of the skin", section on 'Seborrheic keratosis'.)
Dermoscopic evaluation of acquired melanocytic nevi in children most often reveals a globular pattern, especially in lesions located on the head, neck, or upper trunk. In contrast, a reticular pattern is more common in acquired nevi located on the extremities and in children with darker pigmentation, as well as in nevi that develop during adulthood [27]. Histologically, the globular pattern is associated with a prominent dermal component with or without large junctional nests, while the reticular pattern corresponds to a prominent junctional component with lentiginous melanocytic hyperplasia with or without small junctional nests. Acquired nevi with a globular pattern are threefold more likely to have an underlying somatic BRAF V600E activating mutation than those with a reticular pattern (approximately 90 versus approximately 30 percent, respectively) [28].
Management — Most acquired nevi remain benign throughout the lifetime of a person and require no treatment other than longitudinal observation. However, having a large number of acquired nevi increases the risk of melanoma, and patients with multiple acquired nevi should be followed with periodic total body skin examinations and counseled regarding sun protection [29]. (See "Risk factors for the development of melanoma", section on 'Typical nevi' and "Primary prevention of melanoma" and "Melanoma: Clinical features and diagnosis".)
Because more than half of cutaneous melanomas arise de novo (ie, not in association with a nevus), there is no benefit to "prophylactic" removal of nevi. Nevertheless, when melanocytic nevi are removed, no matter what the reason, the specimens should always be sent for histologic examination. (See 'Biopsy considerations' below and "Pathologic characteristics of melanoma".)
ATYPICAL NEVI — Atypical nevi are benign acquired melanocytic nevi that share, usually to a lesser degree, some of the clinical features of melanoma such as asymmetry, border irregularities, color variability, and diameter >6 mm (picture 7A-C). Considerable controversy has surrounded terms such as dysplastic nevus, and the 1992 NIH Consensus Conference recommended the use of the more clinically descriptive term "atypical nevus". They also recommended that the lesions be described histologically as "nevi with architectural disorder," with specification of the degree of melanocytic atypia present (ie, none, mild, moderate, or severe) [30].
Atypical nevi are associated with a total increased number of acquired nevi (eg, greater than 50). In white populations, the prevalence of atypical nevi is approximately 2 to 10 percent [31]. Atypical nevi often do not appear until puberty and are believed to develop throughout life [32]. Their density is generally greater on areas of the body that receive intermittent sun exposure (eg, the trunk and lower extremities) (picture 8) than sites that are not exposed to sun (eg, breast and buttocks). Many patients with multiple nevi exhibit a predominant morphologic type of nevus, or a "signature nevus" [33]. A nevus that has different characteristics from other nevi in a given patient (the "ugly duckling") should be regarded with particular suspicion [34].
The "eclipse" nevus is a type of compound nevus that often develops on the scalp of children and is characterized by a tan center and brown, oftentimes stellate rim (picture 9A-B). Despite their two colors and irregular borders, eclipse nevi have benign behavior and (in the absence of a superimposed concerning feature) do not need to be biopsied or excised [35].
The clinical and dermoscopic features, diagnosis, differential diagnosis, and management of atypical nevi are discussed in detail separately. (See "Atypical (dysplastic) nevi".)
HALO NEVI
Clinical features — The halo nevus (Sutton's nevus) is a melanocytic nevus surrounded by a round or oval, usually symmetric, halo of depigmentation. This pigment loss often heralds the spontaneous regression of the central nevus via a process thought to involve a T-cell mediated immune response to nevus antigens [36]. The halo phenomenon typically involves common acquired melanocytic nevi, but may also be seen with congenital nevi, blue nevi, Spitz nevi, and melanoma.
Halo nevi occur in up to 5 percent of white children 6 to 15 years of age [37,38], and have a higher incidence in patients with an increased number of nevi and a personal or family history of vitiligo. The back is the most common location for halo nevi, and multiple lesions are present in approximately half of cases [37,39].
Any one of four clinical stages can be seen, with the duration of the process ranging from months to several years [40]. The interval between stages I/II and stage IV can be up to a decade [41]:
●Stage I – Pigmented nevus surrounded by a halo of depigmentation (picture 10)
●Stage II – Pink nevus surrounded by a halo of depigmentation (picture 11)
●Stage III – Circular area of depigmentation, with disappearance of the nevus
●Stage IV – Normal-appearing skin after repigmentation of the halo
In some cases, the central nevus may darken rather than lighten, developing hyperpigmentation in a reticular pattern [42]. Hyperkeratotic surface change of the benign central nevus has been reported to occur in some children prior to halo development and also concomitantly with the halo phenomenon [43,44].
Management — It is important to assess the clinical features of the central nevus. A biopsy is not indicated if the central nevus is banal in appearance [45]. Because children with halo nevi often have an increased number of nevi in general, a total body skin examination should be performed. Referral to a dermatologist may be warranted. (See 'Common acquired melanocytic nevi' above.)
If there are atypical or worrisome features, then a biopsy of the central nevus can be performed. However, there is no reason to excise the halo. Although development of multiple halo nevi is not unusual in adolescents and young adults, it is rare in middle-aged and older adults; in the latter population, the possibility of the halo nevi representing an immune reaction to a cutaneous or ocular melanoma must be considered. (See 'Atypical nevi' above and 'Biopsy considerations' below.)
BLUE NEVI
Clinical features — Blue nevi are benign proliferations of dendritic dermal melanocytes that actively produce melanin. The blue color (ceruloderma) is due to the preferential scattering of shorter wavelengths of light by the dermal melanin, a phenomenon known as the Tyndall effect. The sites of predilection of blue nevi (eg, the head and neck, dorsal aspect of the distal extremities, and sacral area) represent locations where active dermal melanocytes are normally still present at the time of birth. (See "Benign pigmented skin lesions other than melanocytic nevi (moles)", section on 'Dermal melanocytoses'.)
Several variants of blue nevi have been described [46]:
●The common blue nevus typically presents as a solitary, uniformly blue to blue-black, dome-shaped papule with preserved skin markings that measures <1 cm in diameter. These nevi often arise in adolescence, and are most often found on the dorsal surface of the hands and feet (picture 12).
●The cellular blue nevus tends to be a larger and more elevated nodule or plaque, measuring at least 1 cm in diameter, with a smooth or slightly irregular surface. Cellular blue nevi may be congenital or acquired, and are most often located on the scalp, buttocks, sacrum, or face.
Most blue nevi have a somatic activating mutation in the GNAQ or GNA11 genes, which encode G-protein alpha-subunits [47]. Occasionally, mutations in KRAS or CYSLTR2 are also seen [48,49].
A hypopigmented variant of blue nevus that lacks the characteristic blue color is occasionally observed. If multiple blue nevi are present, syndromes such as the Carney complex should be considered (table 1) [50]. (See "Cushing's syndrome due to primary pigmented nodular adrenocortical disease", section on 'Carney complex (CNC)'.)
Differential diagnosis — The most common entity in the clinical differential diagnosis of a blue nevus is a traumatic tattoo or pencil-core granuloma, also called graphite foreign body granuloma from implantation of graphite from a pencil [51-53]. This is easily distinguished by history. In addition, blue nevi can resemble nodular melanoma or dermal metastases of melanoma [54]. However, there is typically no history of recent change or growth in blue nevi.
Management — Although small, stable blue nevi require no intervention, lesions appearing suddenly or undergoing clinical change should be biopsied. Because there have been reports of melanoma arising within cellular blue nevi, particularly those located on the scalp, patients with congenital cellular blue nevi that are difficult to follow due to color or location should be referred to a dermatologist for discussion of possible surgical excision [54,55]. (See 'Biopsy considerations' below.)
SPITZ NEVI
Clinical features — Spitz nevi (spindle- and epithelioid-cell nevi) are benign, usually acquired proliferations of melanocytes with histopathologic features that sometimes overlap with those of melanoma. Somatic genetic alterations underlying Spitz nevi range from activating HRAS mutations to fusions involving genes encoding kinases (eg, ALK, ROS1) that stimulate oncogenic signaling [56]. In addition, germline mutations in the BAP1 gene lead to a rare autosomal dominant tumor predisposition syndrome that features spitzoid neoplasms and an increased risk of uveal as well as cutaneous melanoma and other tumors, including mesothelioma and renal cell carcinoma [57]. (See "Spitz nevus and atypical Spitz tumors".)
Spitz nevi often develop during childhood, and they are most commonly located on the face and lower extremities. Lesions tend to present with a rapid initial growth phase that can be alarming to patients and their parents/caregivers.
Spitz nevi classically appear as uniformly pink, tan, red or red-brown, dome-shaped papules or nodules (picture 13A-B). They are usually symmetric, well-circumscribed, and <1 cm in diameter. The surface may be smooth or verrucous, with a clinical appearance that can lead to misdiagnosis as a pyogenic granuloma or wart. Darkly pigmented lesions are occasionally seen, typically exhibiting a symmetric "starburst" dermoscopic pattern with peripheral streaks (picture 14). The pigmented spindle cell nevus of Reed, a variant of the Spitz nevus, characteristically presents in adolescents or young adults as a dark brown to black, thin papule on the thigh (picture 15) [58]. A dermoscopic pattern of pink-tan, structureless areas with irregular dots, globules, or network peripherally raises clinical concern for the familial cancer syndrome associated with BAP1 germline mutations [59]. (See "Spitz nevus and atypical Spitz tumors".)
Management — Clinical monitoring represents an option for a small, stable, clinically classic Spitz nevus in a child [60]. Longitudinal studies have shown that Spitz nevi tend to undergo involution over time [61]. A presumed Spitz nevus with atypical clinical features (eg, diameter >1 cm, asymmetry, or ulceration) should be biopsied with a goal of completely, yet conservatively, removing the lesion. (See "Spitz nevus and atypical Spitz tumors", section on 'Management'.)
BIOPSY CONSIDERATIONS
Possible indications — We do not suggest removal of nevi simply to confirm the presence of architectural disorder histologically. Recognizing the natural history and clinical spectrum of nevi in pediatric patients as well as potentially worrisome findings in this age group can help to avoid unnecessary procedures. Potential indications for biopsy of acquired melanocytic nevi include:
●Nevi on the palms or soles with mottled pigmentation or that are >5 mm in diameter. (See "Pathologic characteristics of melanoma", section on 'Acral lentiginous melanoma'.)
●Nevi originating in the nail matrix that present as single bands of dark color or are ≥4 mm wide; the threshold for biopsy is considerably lower in adults than in children. (See "Overview of nail disorders", section on 'Longitudinal melanonychia'.)
●Nevi with marked asymmetry (based on irregular outline and/or color variation), areas of regression (oftentimes gray-blue or white in color), development of areas of pink or red color, or a history of rapid change or symptoms. (See "Melanoma: Clinical features and diagnosis", section on 'Introduction' and "Melanoma: Clinical features and diagnosis", section on 'Management of suspicious lesions'.)
●An atypical nevus that has different clinical characteristics as compared to the remainder of the nevi in a given patient (ie, the "ugly duckling").
●A halo nevus in which the central nevus has atypical or worrisome features. (See 'Halo nevi' above.)
●A cellular blue nevus that has developed a superimposed change (eg, a papulonodule). (See 'Blue nevi' above.)
●A Spitz nevus with atypical clinical features (eg, diameter >1 cm, asymmetry, or ulceration). (See 'Spitz nevi' above and "Spitz nevus and atypical Spitz tumors".)
An occasional misconception is that the presence of hairs within a melanocytic nevus is a sign of benignity. However, melanoma can develop within congenital nevi (which often contain terminal hairs) and "de novo" cutaneous melanomas can have the same density of terminal hairs as the surrounding skin [62]. Pigmented lesions with features suspicious for melanoma should be biopsied regardless of the presence or absence of hair.
Procedure — The preferred biopsy technique for lesions suspicious for melanoma is one that allows histologic examination of the entire lesion.
Other considerations — It is important to give the dermatopathologist information (eg, foci of eccentric hyperpigmentation) about any pigmented lesion that has been biopsied.
SUMMARY AND RECOMMENDATIONS
●Definition – Acquired melanocytic nevi are benign proliferations of a type of melanocyte known as a "nevus cell." They include common (banal) nevi, atypical nevi, and several additional variants, including halo nevi, blue nevi, and Spitz nevi. (See 'Overview' above.)
●Common nevi – Common (banal) acquired melanocytic nevi tend to be ≤6 mm in diameter and symmetric with a homogeneous surface, even pigmentation, round or oval shape, regular outline, and sharply demarcated border (picture 1). (See 'Common acquired melanocytic nevi' above.)
●Atypical nevi – Atypical nevi are benign acquired melanocytic nevi that share some of the clinical features of melanoma (ie, asymmetry, border irregularities (picture 7C and picture 7A)), color variability, and diameter >6 mm (picture 7B).
Multiple atypical nevi are a phenotypic marker of increased risk of melanoma. The risk of melanoma depends also upon the total number of nevi, family and/or personal history of melanoma, and sun exposure history. (See "Atypical (dysplastic) nevi".)
●Halo nevi – The halo nevus is a melanocytic nevus surrounded by a round or oval halo of depigmentation (picture 10). The halo phenomenon usually involves common acquired melanocytic nevi, but may also be seen with congenital nevi, blue nevi, Spitz nevi, and melanoma. (See 'Halo nevi' above.)
●Blue nevi – Blue nevi are benign proliferations of dendritic dermal melanocytes that actively produce melanin; they typically occur on the head and neck, dorsal aspect of the distal extremities, and sacral area. Multiple blue nevi may indicate a syndrome such as the Carney complex (table 1). (See 'Blue nevi' above.)
●Spitz nevi – Spitz nevi are uniformly pink, tan, red or red-brown, dome-shaped, hairless papules or nodules; they are usually symmetric, well-circumscribed, and <1 cm in diameter (picture 13A). (See 'Spitz nevi' above and "Spitz nevus and atypical Spitz tumors".)
●When to biopsy – We do not suggest removal of nevi simply to confirm the presence of architectural disorder histologically (Grade 2C). However, a biopsy is indicated when the differential diagnosis for a lesion includes early melanoma. (See 'Biopsy considerations' above.)
