Melanocytic nevi are benign neoplasms or hamartomas composed of melanocytes,[1] the pigment-producing cells that constitutively colonize the epidermis. Melanocytes are derived from the neural crest and migrate during embryogenesis to selected ectodermal sites (primarily the skin and the CNS), but also to the eyes and the ears. Ectopic melanocytes have been identified at autopsy in the gastrointestinal and genitourinary tracts. Congenital melanocytic nevi are thought to represent an anomaly in embryogenesis and, as such, could be considered, at least in a sense, malformations or hamartomas.[2] In contrast, most acquired melanocytic nevi are considered benign neoplasms. Compare the images below. Melanocytic nevi occur in all mammalian species and are especially common in humans, dogs, and horses.
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This large congenital nevus developed papular areas of pigmentation within it. Microscopic examination proved that the "new" areas represented small n....
See Can You Recognize Benign Skin Lesions From Cancerous Ones?, a Critical Images slideshow, to help correctly identify various lesions.
The malignant analogue of a melanocytic nevus is melanoma, a topic discussed independently in Malignant Melanoma. Additionally, the Medscape Skin Cancer Resource Center may be helpful.
Melanocytes are present in the basal layer of the epidermis and exhibit a certain degree of territoriality. Non-neoplastic melanocytes typically exhibit contact inhibition to each other, and thus pigment cells are usually not found as contiguous cells. With certain forms of stimulation, such as the exogenous administration of ultraviolet irradiation, the density of melanocytes in normal epithelium may increase. Normal melanocytes may also involve adnexal epithelium, most notably the bulbs of follicular papillae.
Melanocytic nevi represent proliferations of melanocytes that are in contact with each other, forming small collections of cells known as nests. Melanocytic nevi commonly form during early childhood. Their onset is believed by some authorities to be, at least in part, a response to sun (ultraviolet) exposure. However, genetic factors are also clearly involved in the development of some types of melanocytic nevi. Some kinships express an autosomal dominant condition (the so-called dysplastic nevus syndrome or the familial atypical multiple mole and melanoma syndrome), in which members have a large number of large nevi, sometimes hundreds, scattered over the integument.
Melanocytic nevi have also been observed to develop or spread rapidly after blistering events, such as second-degree thermal burns, severe sunburns, or toxic epidermal necrolysis or in persons with genetic blistering diseases such as epidermolysis bullosa. In such instances, the development of so-called eruptive melanocytic nevi appears to be propagated by a traumatic stimulus, with scattering of melanocytic nevus cells over a large area within a zone of blistering and with the subsequent development of multiple independent melanocytic nevi within the injured area. Growth factors, such as basic fibroblast growth factor, have been suggested to be released by proliferating keratinocytes and could contribute to stimulation of melanocyte proliferation in this context. In summary, the exact etiology behind the development of melanocytic nevi is complex and multifactorial and is incompletely understood.
Acquired melanocytic nevi are considered benign neoplasms. In contrast, congenital melanocytic nevi are perhaps best interpreted as congenital malformations. Melanocytes are of neural crest origin, and congenital nevi probably represent an error in the development and migration of these neuroectodermal elements. Evidence of errant embryological migration can be seen histopathologically within giant congenital melanocytic nevi. In this context, melanocytes may be found distributed throughout the dermis, around and within the walls of blood vessels, around adnexal structures such as hair follicles, within the subcutis, and sometimes within skeletal muscle, smooth muscle bundles, nerves, or sebaceous glands.
Errant embryological migration is also believed to be the source of melanocytic nevus cell "rests," which can be observed in the capsules of lymph nodes. Occasionally, rests of melanocytes can also be found in the subcapsular space or within lymph node trabecula. The importance of melanocytic nevus rests is that they can sometimes be mistaken for metastatic deposits because of their extracutaneous location.
These rests are not uncommonly associated with agminated blue or cellular blue nevi or with large congenital melanocytic nevi. However, with the advent of sentinel node evaluation, nodal rests of melanocytic nevi clearly are not uncommon and can be found in association with a variety of melanocytic and nonmelanocytic lesions. These rests of cells are sometimes referred to as benign metastases because these cell clusters may represent the end result of an intralymphatic migration of benign melanocytes. Note, however, that benign nodal melanocytic nevi are almost invariably within the capsule, while melanoma metastases are commonly subcapsular.
The etiology of melanocytic nevi remains unknown. No established genetic or environmental influences are known to contribute to the development of congenital nevi. However, after studying 144 children in Naples, researchers concluded that development of melanocytic nevi early in life is the result of complicated relationships among nevus evolution, anatomic location, and environmental and constitutional factors.[3] The specific genetic factors that contribute to the development of acquired melanocytic nevi also remain unknown. However, data suggest that the propensity for developing large numbers of nevi, such as multiple dysplastic nevi, might be inherited as an autosomal dominant trait.
Patients with the familial atypical multiple mole and melanoma syndrome (also known as the dysplastic nevus syndrome) develop dozens to hundreds of melanocytic nevi and have an elevated lifetime risk for the development of melanoma. As the name implies, this disorder is believed to have an inherited basis.
As noted previously, population-based evidence suggests that ultraviolet irradiation may trigger the development of acquired melanocytic nevi. The number of melanocytic nevi in childhood is inversely related to the degree of skin pigmentation and is high in children with poor sun tolerance. The mechanism of this induction has not been adequately investigated, but such induction could represent an example of tumor promotion by ultraviolet light.
Acquired melanocytic nevi are so common that some authorities believe they cannot be considered a defect or an abnormality. However, despite the high prevalence, melanocytic nevi are nonetheless pathologic in the sense that they represent an aberrant or neoplastic proliferation of cells. Most persons with light skin have at least a few melanocytic nevi.[4] Melanocytic nevi also occur in dark-skinned individuals, albeit with low prevalence. Interestingly, there are distribution differences in melanocytic nevi between light-skinned and dark-skinned individuals. In light-skinned individuals, most melanocytic nevi occur on the trunk. In dark-skinned individuals, acral melanocytic nevi are relatively more common.[5]
International
The international prevalence of melanocytic nevi is believed to be similar to that observed in the United States. The prevalence in ethnic groups with dark skin is lower than that observed in individuals with fair skin. If ultraviolet exposure represents an inducing agent for the development of melanocytic nevi, than this is unsurprising. Some individuals of northern European extraction, especially those from northern Germany, Holland, Belgium, and the United Kingdom, not uncommonly have large nevi (≥ 1 cm in largest diameter), often of large number (>50, up to several hundred), with a red-brown color. These nevi have been called atypical moles or dysplastic nevi.
Race
Melanocytic nevi are common lesions in patients with light or fair skin and are less common lesions in dark-skinned individuals. This difference in prevalence is in part attributable to the fact that identifying moles in dark-skinned patients is often difficult, especially if the lesions are macular (flat).
Some authorities have suggested that melanocytic nevi are in part stimulated by exposure to sunlight.[6, 7] If so, then individuals with dark skin might have fewer nevi because of the protective properties of melanin.
Evidence indicates that broad-spectrum sunscreens attenuate the development/evolution of melanocytic nevi when used in children[8] ; therefore, dark-skinned individuals probably have inherent protection against the development of moles because of their cutaneous melanization.
Sex
No clear sex predilection is reported for the development of melanocytic nevi. However, melanocytes have been postulated to exhibit some degree of sex hormone responsiveness. The findings associated with melanocytic nevi during pregnancy support this conclusion. Melanocytic nevi commonly darken and/or enlarge during pregnancy. Melanocytes have been shown to have cytosolic receptors for estrogens and androgens, and melanogenesis is responsive to these steroid hormones. Some melanomas seem to respond to hormones, an observation that might be explained by these cytosolic receptors.
Subtle differences may exist in the prevalence of melanocytic nevi between women and men. Judging the incidence and prevalence based on available biopsy data is difficult because women may be more likely to seek medical attention. If sex-specific variations in incidence do exist, the differences may be site specific. For example, specific histopathological features are commonly observed in melanocytic nevi that occur within genital skin. These features are noted almost exclusively within biopsy specimens from women, although similar alterations can occasionally be observed in melanocytic nevi from males.
From the author's database (at the University of California, San Francisco), data clearly show that biopsies of genital melanocytic nevi are much more commonly performed in women than in men. These data do not unequivocally confirm that the prevalence of genital melanocytic nevi is truly increased in women, although this seems likely.
Age
By definition, congenital melanocytic nevi are present at birth or soon thereafter, although some small congenital nevi are clearly tardive in their clinical presentation. Current opinion holds that some elements of such nevi are present at birth but remain inconspicuous until some later date.
By definition, acquired melanocytic nevi are not present at birth, and the incidence of melanocytic nevi increases throughout the first 3 decades of life.
The peak incidence of melanocytic nevi is in the fourth to fifth decades of life, and the incidence with each successive decade decreases, with a low incidence in elderly persons.
Acquired melanocytic nevi have been stated to be absent at birth and at death. Although not entirely true, this concept reflects the fact that acquired nevi develop in increasing numbers throughout childhood and early adulthood and then slowly involute; therefore, melanocytic nevi are inconspicuous during the advanced elder years.
Nevus subtype incidence may also vary with ages. According to a study by Zalaudek et al, melanocytic nevi of mixed pattern with a peripheral rim of dark globules are sufficiently rare in persons older than 50 years that they should be considered suspicious.[9]
The prognosis associated with any single melanocytic nevus is favorable because these lesions are benign neoplasms with no potential for malignant behavior, unless evolution of melanoma occurs. Patients with multiple melanocytic nevi or sizable melanocytic nevi appear to have an increased lifetime risk of melanoma, with the risk increasing in rough proportion to the size and/or number of lesions.
Melanocytic nevi, if diagnosed properly, are biologically stable, completely benign lesions. However, melanocytic nevi can be found in association with melanoma.[10] The true frequency of transformation of a melanocytic nevus into melanoma is not known, and the estimated prevalence varies widely in published series, with some data suggesting that up to 40% of melanomas are associated with a precursor melanocytic nevus.
Both acquired and congenital melanocytic nevi hold some risk for the development of melanoma. Congenital melanocytic nevi hold the greater risk, and this is especially true of giant congenital melanocytic nevi. This is believed to be a consequence of the fact that the number of lesional melanocytes within large lesions is greater, and thus the chances of a transformative event are proportionately greater. Large and giant congenital melanocytic nevi often have both biological and cosmetic implications. Large congenital nevi have a low but real risk for secondary malignant transformation and the development of melanoma. Some data suggest that melanoma can develop within a giant congenital melanocytic nevus in up to 5% of cases.
Patients should be educated regarding self-examination of melanocytic nevi. Teach patients to use an ABCDE approach, in which the patient assesses the asymmetry, border irregularity, color, diameter (size), and evolution of any given lesion. Some authorities add an F for "funny looking," suggesting that "ugly duckling" lesions that differ from the patient's other nevi should be evaluated. An explanation of any changes and observations for changes are important. Nevi can change in diameter, outline, and/or color, and they can acquire an itch or begin to bleed. These changes require evaluation by a trained observer to determine the malignant potential of a lesion.
Patient handouts that illustrate these changes and their significance are available from the American Academy of Dermatology. The greater the degree of asymmetry, the greater the irregularity in the border, the greater the variation in color, and the greater the diameter of the lesion, the more cause for concern.
The need for adequate sun protection and should be emphasized to adults and children.[11]
For patient education resources, see the patient education article Mole Removal.
Melanocytic nevi are common lesions that can be found on the integument of almost all individuals. Some patients present with few lesions, while others have hundreds. The number on a given individual increases in rough proportion to the degree of skin pigmentation.
Melanocytic nevi can be broadly divided into congenital and acquired types. Determining if a lesion is congenital or acquired is generally easily accomplished by direct query of the patient, although, as noted above, some small congenital melanocytic nevi are tardive and may be perceived by the patient as acquired.
When evaluating the nature of a melanocytic lesion, a number of attributes must be assessed. Further commentary describing physical attributes can be found in Physical. Whether a lesion has become symptomatic (eg, itchy, painful, irritated, or bleeding) is considered an important indicator of potential malignant change.
Not all melanocytic nevi that change are malignant, especially if change is noted in a person younger than 40 years. However, change that is perceptible over a short time is an indicator of potential malignancy and designates a lesion deserving of biopsy. An Australian study found that 16% of benign lesions changed (as measured by sequential digital dermoscopic imaging) over an interval of 2.5-4.5 months. The proportion of benign lesions that changed was higher in persons aged 0-35 years than in those aged 36-65 years but rose again in the elderly (age >65 y).[12]
Acquired melanocytic nevi are typically less than a centimeter in diameter and evenly colored.
Melanocytic nevi most commonly are tan to brown, but coloration can be variable, ranging from skin-colored (nonpigmented) to jet black. The deep pigmentation associated with dark melanocytic nevi often stems from associated intracorneal pigmentation. The spectrum of "hypermelanotic" melanocytic nevus includes lesions with heavy epidermal pigmentation.
Dysplastic melanocytic nevi have also been referred to as Clark nevi.[13] The designation "dysplastic" was applied to such lesions because of an early belief that such lesions might be biologically unstable and represent common precursors of melanoma. Further study has not definitively confirmed that this is the case. Dysplastic nevi present clinically as flattish, pigmented macules or thin papules. Often, a "fried egg" configuration is apparent, with a central papular area that is flanked by a macular zone of deeper pigmentation.
Spitz nevi represent another distinctive variant of melanocytic nevus. In decades past, such lesions were referred to as "juvenile melanomas," but now they are recognized by specific microscopical features and are believed to be benign. Although Spitz nevi tend to manifest as pink papules on the head of a child, they can be clinically indistinguishable from conventional nevi in some instances; they also can be heavily pigmented. Heavily pigmented Spitz nevi may also be referred to as "Reed nevi" or "pigmented spindle cell nevi." Many Spitz nevi exhibit considerable associated vascular ectasia and, thus, display a hemangiomalike clinical appearance.
Blue nevi represent melanocytic nevi with a dermal distribution of cellularity and spindled cytomorphology under the microscope. Such lesions are typically heavily pigmented. Because of the presence of deep pigmentation within a refracting colloidal medium (namely, the skin), the brownish-black pigment present contributes a bluish cast to such lesions, thereby explaining the name. The optical effect that accounts for clinical blueness is known as the Tyndall phenomenon. The Tyndall phenomenon is not unique or exclusive to blue nevi. Any melanocytic nevus with deep pigmentation may present clinically with a blue hue.
Not all blue nevi are blue. Some present with various shades of gray, brown, or black. The clinical appearance varies depending on the degree of clinical pigmentation. Indeed, some blue nevi may be wholly amelanotic. Because of the fact that the term blue nevus is not always reflective of the true clinical appearance of the lesion, some dermatopathologists name blue nevi based on the cellular morphology present. The terms spindle cell melanocytic nevus or dendritic melanocytic nevus represent morphological terms that refer to the spectrum of blue nevi.
Despite their variability in coloration, blue nevi are usually relatively small and reasonably symmetric, as typically is the case in benign lesions. Some blue nevi may be large and nodular with high cellularity under the microscope. Blue nevi typically occur on the distal extremities or scalp, but they can occur at any body site.
Physical examination involves, at a minimum, careful visual inspection of the lesion in question; in some instances, an examination of the entire skin surface should be performed. Importantly, document the dimensions and coloration of any lesion evaluated and record its exact location. A simple drawing of the lesion and the overall topography can be helpful. Many dermatologists use topographic charts to record the location of multiple lesions that are monitored from visit to visit. Some dermatologists enumerate individual lesions to facilitate follow-up. For some patients, especially those with multiple melanocytic nevi, photographic documentation of lesions (including both distant views that demonstrate topography and close views that capture subtle features of a particular lesion) can be valuable. When examining melanocytic nevi, the physician should examine the scalp (possibly with the aid of a hair dryer), the palms, the soles, between the toes, and the genitalia.
Congenital melanocytic nevi
Congenital melanocytic nevi vary considerably in size and are commonly classified as small (< 1 cm), intermediate (1-3 cm), or large/giant (>3 cm).
Congenital melanocytic nevi are generally relatively evenly pigmented and tan or brown, especially those that are thin. In some congenital nevi, the cells extend from the level of the epidermis to the subcutaneous fat. These lesions can have an array of colors, and, at times, they cannot be easily distinguished from melanoma based solely on findings from the clinical evaluation.
Congenital melanocytic nevi are hamartomalike; that is, they contain a predominance of melanocytes but also seem to have simultaneous accentuation of other cutaneous elements. Thus, an increase in the number of hair follicles, the presence of follicles of increased size, or an increase in other appendages may be observed.
Conventional or common acquired melanocytic nevi
Conventional or common acquired melanocytic nevi are generally less than 1 cm in diameter and evenly pigmented. Some atypical melanocytic nevi (melanocytic nevus of the so-called Clark or dysplastic type) exceed 1 cm in size, especially when such lesions occur on the trunk.
Junctional melanocytic nevi are macular or thinly papular. Junctional lesions typically range from brown to brownish-black. The darker coloration of junctional melanocytic nevi stems from the fact that the surface epidermis is often simultaneously hyperpigmented.
Compound and intradermal melanocytic nevi display elevation relative to surrounding uninvolved skin. Compound melanocytic nevi are often lighter in color than junctional nevi and range from tan to light brown. Some compound melanocytic nevi have areas of dark pigmentation, particularly those that have been recently irritated or traumatized. Many wholly intradermal melanocytic nevi display no significant pigmentation.
The development of a new area of pigmentation within a long-standing nonpigmented or lightly pigmented compound or intradermal melanocytic nevus, as shown in the image below, is a cause for concern. While pigmentary changes could be due to incidental inflammation or recent irritation or trauma, the possibility of evolving melanoma is also a consideration in the differential diagnosis. Generally, a biopsy for microscopic examination is warranted in this context.
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A conventional (papular) melanocytic nevus occurring within acral skin. Note slight border irregularity, a feature common in association with acral ne....
Dysplastic or atypical nevi
Dysplastic or atypical nevi (also known as Clark nevi) are acquired variants that are relatively flat, thinly papular, and relatively broad. Often, such lesions exhibit target-like or fried egg–like morphology, as noted above, with a central papular zone and a macular surrounding area with differing pigmentation.
Dysplastic nevi often occur in a familial fashion. Affected individuals may present with dozens or hundreds of such lesions. Almost invariably, individuals with dysplastic nevi are of northern European ancestry from the United Kingdom, the Netherlands, Germany, or, occasionally, Poland or Russia. Most of these individuals have fair skin and other Celtic features. Some individuals have only a few atypical nevi, and their risk of melanoma may not be much higher than persons without such nevi. Persons with large numbers of nevi (>100) have a high lifetime risk of melanoma that approaches unity. Persons with large numbers of nevi and a familial history of melanoma (consisting of ≥ 2 members of the primary family with melanoma) have an extremely high risk of developing melanoma and deserve vigilant clinical monitoring.
Dysplastic nevi generally grow through lateral extension of the intraepidermal component of the lesion; therefore, these lesions often assume the clinical configuration of a fried egg, with a central papular zone and a surrounding macular area of differing pigmentation. The peripheral border is often perceived as blurred or fuzzy because of this lateral extension of superficial melanocytes.
Some authorities have postulated that Clark (dysplastic) nevi (shown below) are significant or common precursors to melanoma. The designation dysplastic was chosen to suggest that these lesions represent an intermediate (unstable) form between conventional nevi and melanoma. This concept remains controversial. They may represent precursor lesions, markers for an increased risk of de novo melanoma, or both. Some data suggest that most melanomas in patients with the dysplastic nevus syndrome occur de novo. While the removal of all dysplastic nevi from an individual with melanoma is generally not indicated, removal of lesions with a highly atypical appearance is indicated to be certain that melanoma is not present.
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A Clark (dysplastic) nevus with modest variation in pigmentation and irregular borders. Biopsy of the lesion proved no evidence of melanoma.
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A compound Clark (dysplastic) nevus with fried egg–like clinical morphology, with a central dark papule flanked by an eccentric more lightly pigmented....
Spitz nevi
Spitz nevi (shown below) vary considerably in size, but they generally are smaller than 1 cm in diameter.
Many Spitz nevi have a keratosislike quality because of associated epidermal hyperplasia and hyperkeratosis, and some have an angiomalike appearance because of associated vascular ectasia.
The degree of pigmentation of Spitz nevi also varies; a heavily pigmented, small, spindle cell variant on the legs of women has been referred to as "pigmented spindle cell nevus" or "Reed nevus" because the pigmented spindle cell variant was described by Richard Reed.
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A heavily pigmented junctional Spitz nevus, also known as pigmented spindle cell nevus. Note that many Spitz nevi are nonpigmented and may have an ang....
Blue nevi
Blue nevi are not always blue, and they are not even always pigmented. The designation blue nevus, although flawed, has been preserved for historical reasons.
Blue nevi are sometimes larger than other melanocytic nevi, occasionally measuring 2 cm or greater in diameter. This is particularly true of cellular lesions (cellular blue nevi) that occur at sun-protected sites, such as the buttocks.
Blue nevi are often firm because of associated stromal sclerosis, and they often have a nodular quality, a reflection of their deeper position within the skin.
Heavily pigmented blue nevi manifest clinically as blue, black, or gray lesions, whereas blue nevi with lesser degrees of pigmentation may be tan or brown or strictly the color of surrounding healthy skin.
Hypocellular blue nevi that cover an extensive clinical distribution have been referred to as "dermal melanocytic hamartomas" by some authors. This spectrum includes the entities nevus of Ito, nevus of Ota, and nevus of Sun.
No known complications are directly related to the presence of melanocytic nevi; however, minor surgical intervention during the biopsy or the removal of such lesions can lead to common complications (eg, infection, hemorrhage).
No laboratory studies are indicated in the evaluation of common acquired melanocytic nevi. As a rule, patients with congenital melanocytic nevi also do not require laboratory evaluation.
Imaging is not warranted in the evaluation of most patients with acquired melanocytic nevi; however, the possibility of neurocutaneous melanosis should be considered in patients (children) with multiple congenital melanocytic nevi involving the skin overlying the spine and the posterior part of the scalp.
Some patients with multiple congenital nevi overlying the CNS warrant radiologic imaging. Such individuals are at risk for leptomeningeal melanosis. Some patients with neurocutaneous melanosis have nests of melanocytes within the CNS at specific sites. These nests of cells can be detected using MRI (especially with T1-weighted images).[14] Although the nests of melanocytes are benign, these cells pose a risk for transformation to CNS melanoma, and follow-up care is indicated.
Simple excisional biopsy is the procedure of choice for removal and diagnosis of a melanocytic nevus. All removed melanocytic nevi should be submitted for microscopic evaluation. Because the interpretation of pigmented lesions may be challenging, many dermatologists prefer to have their specimens read by a qualified dermatopathologist.[15, 16]
Either shave biopsy or punch biopsy is typically used for cosmetic removal of banal melanocytic nevi.
It is optimal to strive for complete excision of a given lesion, if at all possible, when melanoma is considered in the differential diagnosis.
A complete excisional biopsy permits all available histopathological criteria to be applied to a lesion and thus enables a more precise diagnosis.
When a partial punch or shave biopsy sample is taken from a lesion, the interpreting pathologist cannot apply important criteria, such as symmetry and circumscription (lateral demarcation), to the assessment of the lesion. If a partial biopsy specimen of a larger lesion is obtained because of clinical necessity, the fact that the specimen is partial should be clearly indicated on the requisition form.
Partial biopsy samples can sometimes lead to misdiagnosis because of sampling error.
Partial biopsy samples can inflate the number of procedures required for diagnosis because a partial biopsy sample that does not enable a definitive diagnosis to be made necessarily leads to subsequent reexcision of the lesion in question.
The chief histopathological differential diagnosis involves the distinction of melanoma from various forms of melanocytic nevi, including Spitz nevi. Examination via conventional microscopy remains the criterion standard for making this distinction. Genomic analysis via comparative genomic hybridization (CGH) or fluorescence in situ hybridization (FISH) is being used on a limited basis to supplement conventional histopathological interpretation. Genomic analysis permits screening of fixed tumor tissue for cytogenetic aberrations. To date, studies indicate that multiple cytogenetic flaws are typical of melanoma, whereas most melanocytic nevi are cytostructurally normal.
Most melanocytic nevi develop along the dermoepidermal junction, where normal melanocytes are positioned within the lower-most part of the epidermis. Melanocytes are also distributed in smaller numbers within the dermis; therefore, wholly dermal nevi can occur. Melanocytic nevi that are exclusively dermal include the group of lesions referred to as blue nevi.
Melanocytic nevi can be categorized on the basis of the phenotype (cytological appearance) of the melanocytes that make up the lesion. Benign neoplastic melanocytes (sometimes referred to as nevus cells) most commonly have round/ovoid nuclei, scant cytoplasm, and a predilection to form nests and syncytia. However, melanocytes are morphologically nimble cells that can assume a wide variety of appearances, including spindled, epithelioid, and dendritic forms. Nuclear hyperchromasia, nuclear molding, atypical mitoses, and a pepper-moth chromatin pattern suggest melanoma rather than nevus.[17]
Assessing the architecture of any melanocytic neoplasm is imperative as one of the first steps in evaluation. Most melanocytic nevi are relatively small, most are reasonably symmetrical, and most show fairly sharp lateral demarcation or circumscription. Melanomas typically show the converse of these features. Many (but not all) melanocytic nevi are arrayed as nests and fascicles of cells, and the nests and the fascicles of cells are usually relatively uniform in size and shape. In contrast, marked variation in nest size and shape should amplify concern regarding the possibility of melanoma. Lesional melanocytic in a nevus typically appear smaller, microscopically, with descent in the dermis. See the image below. This phenomenon is referred to as maturation.
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Histopathologically, a congenital nevus differs from an acquired melanocytic nevus in that melanocytes are often distributed deeply within the reticul....
Conventional (ordinary or common acquired) melanocytic nevi develop as a proliferation of single melanocytes along the dermoepidermal junction. As the melanocytes proliferate, small nests of cells develop in the lower-most part of the epidermis, and the resultant lesion is termed a junctional melanocytic nevus. With continued proliferation, nests persevere along the junction, but they can also be found within the superficial dermis, a configuration termed compound melanocytic nevus. As a nevus ages, the junctional component often diminishes or entirely involutes. The resultant nevus is termed an intradermal melanocytic nevus, depicted below.
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A conventional compound melanocytic nevus. Note the presence of melanocytes with small nuclei in nests along the dermoepidermal junction and the prese....
Congenital melanocytic nevi are similar to their acquired counterparts in that junctional, compound, and intradermal patterns can be seen. Most congenital nevi extend well into the dermis, with melanocytes positioned in the interstitial dermis between collagen bundles. The depth of extension into the dermis is variable. Some large congenital nevi exhibit cells that extend into subcutaneous septa. Congenital melanocytic nevi with melanocytes confined to the upper half of the reticular dermis have been termed superficial congenital nevi. Lesions of this type are typically smaller than 2 cm in overall diameter.
Spitz nevi, shown below, are virtually always acquired melanocytic nevi, and they can exhibit a microscopic pattern that is junctional, compound, or wholly intradermal. Like all benign nevi, Spitz nevi tend to be relatively small and symmetrical and laterally demarcated, but Spitz nevi differ from conventional nevi in that nucleomegalic cells are common and predominate in some lesions. Such nucleomegalic Spitz nevus cells may be aneuploid, tetraploid, or octoploid. The explanation as to why Spitz nevi are commonly nondiploid while lacking other attributes of malignancy has not yet been forthcoming. Clearly, anomalies in ploidy alone are not sufficient for full malignant transformation. Data from 2016 suggest that mutations in CDKN2A and resulting loss of p16 expression are associated with atypical Spitz tumors and spitzoid melanoma.[18]
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This Spitz nevus shows large melanocytes with spindled and epithelioid cytomorphology arrayed along the junctional zone of an acanthotic and hyperkera....
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At higher magnification, this Spitz nevus also demonstrates large, dull-pink globules along the junctional zone. These structures are known as Kamino ....
Overlap in the morphology of melanocytic nevi can occur. For example, occasional melanocytic nevi can display overlap between the morphology of Spitz nevus and dysplastic nevus. Overlap between blue and Spitz nevi can also be seen. Such lesions have been humorously referred to as “Sparks” (Spitz + Clarks) or “blitz” (blue + Spitz) nevi.[19]
When more than one type of cellular morphology occurs in a melanocytic nevus, the lesion is referred to as a combined melanocytic nevus. Conventional melanocytic nevi are commonly combined with Spitz or blue nevi.
Blue nevi, shown below, are typically largely or entirely dermal melanocytic neoplasms composed of spindled and/or dendritic melanocytes with heavy cytoplasmic pigmentation. Some blue nevi are composed of epithelioid melanocytes, especially the deeply extending variant designated deep penetrating nevus, and many exhibit considerable associated sclerosis. The designation blue is far from the truth in many, if not most, instances because melanocytic nevi with spindled and dendritic melanocytes can be tan, brown, black, gray, or even skin-colored; however, despite its inaccuracy, the designation blue nevus remains the universal standard for this category of lesions.
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This blue nevus is composed of small dendritic melanocytes. This type of cytomorphology can be seen in so-called common blue nevi and in topographical....
Some authorities have promoted the use an eponymic approach to the classification of melanocytic nevi. The merit of this proposal derives from the fact that eponymic naming avoids the semantic misdeeds of the past. For example, the benign entity formerly (and incorrectly) known as juvenile melanoma becomes a Spitz nevus in the eponymic system. Dysplastic nevi are eponymically known as Clark nevi, in memory of Wallace Clark. The designation Miescher nevus can be used to designate dome-shaped, superficial congenital nevi that are commonly expressed on the face and the upper part of the trunk, whereas the designation Unna nevus can be used to refer to acrochordonlike lesions that commonly develop near skin folds.[20, 21]
Despite the enthusiasm for eponymic naming in some areas, the usage of such designations can impede communication with the uninitiated. The author sees no difficulty in the usage of eponyms (and uses eponyms sporadically in his own practice), as long as the exact nature of the lesion in question is clearly stated in the language of the pathology report.
Melanocytic nevi are benign lesions. No staging is required, with the possible exception of atypical benign lesions for which uncertainty exists regarding the diagnosis and melanoma cannot be entirely eliminated from the differential diagnosis.
Melanocytic nevi can be surgically removed for cosmetic considerations or because of concern regarding the biological potential of a lesion.
Melanocytic nevi removed for cosmesis are often removed by tangential or shave excision.
Punch excision can be used for relatively small lesions.
Large lesions may require complete excision with sutured closure, even if known to be benign, because lesions exceeding 1 cm in diameter often are not amenable to the shave technique.
A simple conservative excisional biopsy with a sutured closure is usually the most expeditious means to diagnosis if concern exists regarding the possibility of melanoma. If the lesion is found to be benign, then, ordinarily, no further treatment is required.
Providing the pathologist with a complete excisional specimen affords him or her the best opportunity to make an accurate diagnosis because all available criteria (including low-magnification attributes such as size, circumscription, and symmetry) can be applied to the lesion.
If a partial biopsy is obtained, information regarding the size and appearance of the lesion that underwent biopsy should be forwarded to the interpreting pathologist or dermatopathologist.
Interpreting partial biopsy samples of melanoma is not prudent, especially for pathologists with limited experience in the microscopic evaluation of melanocytic neoplasms; not uncommonly, it can lead to a false diagnosis of nevus. If a biopsy specimen represents a partial sample of a larger lesion, the clinician should clearly indicate this to the dermatopathologist or pathologist on the requisition form. If any atypical feature is present, a second opinion from an expert dermatopathologist should be pursued.
Studies have clearly demonstrated that experience is an important factor in the clinical diagnosis of cutaneous pigmented lesions, including both melanocytic nevi and melanoma.
Any generalist or primary care physician should have a low threshold for referral to a dermatologist when questions exist regarding the clinical diagnosis and management of a pigmented lesion. If a dermatologist is not locally available, a generalist with a digital camera can find teledermatology resources readily available via the Internet.
Once a biopsy has been performed on a lesion and a histopathological diagnosis has been made, strong consideration should be given to the possibility of consultation with a board-certified dermatopathologist if the primary diagnosis has been issued by a general pathologist. This is especially true if the diagnosis of melanoma has been forwarded or if the histopathological diagnosis is discordant with the original clinical diagnosis.
Consultation with an experienced physician, typically a dermatologist, is indicated if any concern exists regarding a pigmented lesion.
Preliminary evidence suggests that childhood ultraviolet radiation exposure is correlated with the number of melanocytic nevi that develop in subsequent years.[22] If this is presumed to be true, then measures to limit ultraviolet light exposure (eg, wearing sunscreen, providing sun education) might yield reductions in the incidence of melanocytic nevi and melanoma over time.[23, 24, 25]
Timothy McCalmont, MD, Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco; Editor-in-Chief, Journal of Cutaneous Pathology
Disclosure: Received consulting fee from Apsara for independent contractor.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Rosalie Elenitsas, MD, Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
James J Nordlund, MD, Professor Emeritus, Department of Dermatology, University of Cincinnati College of Medicine
This large congenital nevus developed papular areas of pigmentation within it. Microscopic examination proved that the "new" areas represented small nodular collections of benign melanocytes, with no evidence of evolving melanoma.
A conventional (papular) melanocytic nevus occurring within acral skin. Note slight border irregularity, a feature common in association with acral nevi.
A Clark (dysplastic) nevus with modest variation in pigmentation and irregular borders. Biopsy of the lesion proved no evidence of melanoma.
A compound Clark (dysplastic) nevus with fried egg–like clinical morphology, with a central dark papule flanked by an eccentric more lightly pigmented macular zone.
A heavily pigmented junctional Spitz nevus, also known as pigmented spindle cell nevus. Note that many Spitz nevi are nonpigmented and may have an angiomalike clinical appearance.
Histopathologically, a congenital nevus differs from an acquired melanocytic nevus in that melanocytes are often distributed deeply within the reticular dermis, within the adventitial dermis around adnexal elements, and sometimes within the subcutis. This congenital nevus shows a folliculocentric array of melanocytes.
A conventional compound melanocytic nevus. Note the presence of melanocytes with small nuclei in nests along the dermoepidermal junction and the presence of similar melanocytes in nests and syncytia in the subjacent dermis.
This Spitz nevus shows large melanocytes with spindled and epithelioid cytomorphology arrayed along the junctional zone of an acanthotic and hyperkeratotic epithelium.
At higher magnification, this Spitz nevus also demonstrates large, dull-pink globules along the junctional zone. These structures are known as Kamino bodies. Kamino bodies are most commonly observed in association with Spitz nevi but are occasionally observed in melanocytic nevi of other types. Well-formed Kamino bodies are almost never (if ever) found in association with melanoma.
This blue nevus is composed of small dendritic melanocytes. This type of cytomorphology can be seen in so-called common blue nevi and in topographically restricted lesions such as nevus of Ito or nevus of Ota.
A Clark (dysplastic) nevus with modest variation in pigmentation and irregular borders. Biopsy of the lesion proved no evidence of melanoma.
A compound Clark (dysplastic) nevus with fried egg–like clinical morphology, with a central dark papule flanked by an eccentric more lightly pigmented macular zone.
A conventional (papular) melanocytic nevus occurring within acral skin. Note slight border irregularity, a feature common in association with acral nevi.
A heavily pigmented junctional Spitz nevus, also known as pigmented spindle cell nevus. Note that many Spitz nevi are nonpigmented and may have an angiomalike clinical appearance.
A melanocytic nevus occurring within conjunctival epithelium.
A conventional compound melanocytic nevus. Note the presence of melanocytes with small nuclei in nests along the dermoepidermal junction and the presence of similar melanocytes in nests and syncytia in the subjacent dermis.
This Spitz nevus shows large melanocytes with spindled and epithelioid cytomorphology arrayed along the junctional zone of an acanthotic and hyperkeratotic epithelium.
At higher magnification, this Spitz nevus also demonstrates large, dull-pink globules along the junctional zone. These structures are known as Kamino bodies. Kamino bodies are most commonly observed in association with Spitz nevi but are occasionally observed in melanocytic nevi of other types. Well-formed Kamino bodies are almost never (if ever) found in association with melanoma.
This blue nevus is composed of small dendritic melanocytes. This type of cytomorphology can be seen in so-called common blue nevi and in topographically restricted lesions such as nevus of Ito or nevus of Ota.
This large congenital nevus developed papular areas of pigmentation within it. Microscopic examination proved that the "new" areas represented small nodular collections of benign melanocytes, with no evidence of evolving melanoma.
Histopathologically, a congenital nevus differs from an acquired melanocytic nevus in that melanocytes are often distributed deeply within the reticular dermis, within the adventitial dermis around adnexal elements, and sometimes within the subcutis. This congenital nevus shows a folliculocentric array of melanocytes.
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