Dermoscopy of nevi and melanoma in childhood

Abstract

Dermoscopy is a noninvasive technique that allows for the visualization of subsurface colors and structures within pigmented melanocytic skin lesions that are otherwise imperceptible to the naked eye. Dermoscopic findings have been formulated into diagnostic criteria that assist experienced clinicians in differentiating benign and malignant neoplasms. In essence, dermoscopy can help identify cutaneous malignancies, while at the same time minimizing the frequency of unwarranted biopsies of benign cutaneous lesions. In this article, we examine the clinical morphology of melanocytic nevi and melanoma in the pediatric population, and describe the relevant dermoscopic findings and histopathologic correlates that aid in the diagnosis and management of these lesions.

Keywords::

• acquired melanocytic nevi
• blue nevi
• congenital melanocytic nevi
• dermoscopy
• halo nevi
• lentiginous nevus
• melanoma
• nevus spilus/speckled pediatric
• Spitz nevi

Medscape: Continuing Medical Education Online

This activity has been planned and implemented in accordance with the Essential Areas and poli¬cies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Expert Reviews Ltd. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Medscape, LLC designates this Journal-based CME for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with their participation in the activity.

All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://www.medscape.org/journal/expertderm (4) view/print certificate.

Release date: February 7, 2011; Expiration date: February 7, 2012

Learning objectives

Upon completion of this activity, participants should be able to:

• • Describe the potential advantages and disadvantages of dermoscopy of melanocytic lesions in children

• • Describe how dermoscopy can help differentiate benign from malignant melanocytic lesions in children

• • Describe how dermoscopy can facilitate work-up and management of melanocytic lesions in children

• • Describe classification of melanocytic lesions in children

Financial & competing interests disclosure

EDITOR

Elisa Manzotti,Editorial Director, Future Science Group, London, UK

Disclosure:Elisa Manzotti has disclosed no relevant financial relationships.

CME AUTHOR

Laurie Barclay, MD,Freelance writer and reviewer, Medscape, LLC

Disclosure:Laurie Barclay, MD, has disclosed no relevant financial relationships.

AUTHOR

Christine Brooks, DO,St Joseph Mercy Health System, Pontiac, MI, USA

Disclosure:Christine Brooks, DO, has disclosed no relevant financial relationships.

Alon Scope, MD,Sheba Medical Center, Tel Hashomer, Israel

Disclosure:Alon Scope has disclosed no relevant financial relationships.

Ralph P Braun, MD,Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

Disclosure:Ralph P Braun, MD, has disclosed no relevant financial relationships.

Ashfaq A Marghoob, MD,Memorial Sloan-Kettering Cancer Center, NY, USA

Disclosure:Ashfaq A Marghoob, MD, has disclosed no relevant financial relationships.

Figure 1. Congenital melanocytic nevus.

The congenital melanocytic nevus displays an organized and symmetric pattern with a peripheral network pattern with central globules. The lesion also has a few milia cysts and hypertrichosis, which are structures commonly observed in congenital melanocytic nevus.

Figure 2. Congenital melanocytic nevus with a disorganized, multicomponent pattern.

In the presence of a focal network, irregular globules and an irregular blotch, melanoma should be definitively ruled out.

Figure 3. Schematic depiction of the ten most common patterns encountered in benign melanocytic nevi.

Figure 4. Congenital melanocytic nevus of the lower extremity.

A reticular pattern is seen and the network is interrupted by follicular openings (hypertrichosis). Perifollicular hypopigmentation is a common feature seen in congenital melanocytic nevus.

Figure 5. Cobblestone congenital melanocytic nevus.

Globules of differing sizes with angulation and crowding of the globules create a characteristic cobblestone pattern.

Figure 6. Target network with globules within a congenital melanocytic nevus.

Figure 7. Atypical small congenital melanocytic nevus.

This lesion does not manifest the benign dermoscopic patterns illustrated in Figure 3. Half of the lesion reveals an organized pattern with cobblestone globules, hypertrichosis and milia cysts, which are all common features of congenital melanocytic nevus. The other half of the lesion is disorganized with irregular network, dots and peppering. This lesion was excised and histopathology confirmed the diagnosis of melanoma arising in a small congenital melanocytic nevus.

Figure 8. Acquired melanocytic nevus showing a peripheral network with central hypopigmentation.

Figure 9. Acquired melanocytic nevus.

Acquired melanocytic nevus showing a peripheral network with central hyperpigmentation.

Figure 10. Enlarging acquired melanocytic nevus.

The presence of a peripheral rim of globules is an indicator that the nevus has not yet entered senescence. It can be predicted that nevi displaying this pattern will enlarge symmetrically over time. Once the nevus enters senescence, it will stop growing and the peripheral rim of globules will no longer be visible. The nevus in these images was followed over the course of 2 years. The first image was taken at baseline, the second image was acquired at 9-month follow-up and the last image was obtained at the 17-month follow-up visit.

Figure 11. Halo nevus.

This globular nevus is surrounded by a halo of depigmentation. This nevus became smaller over time and eventually disappeared over the course of a 4-year period. The first image (A) was obtained at baseline, the second image (B) at the 1-year follow-up visit, the third image (C) at the 3-year follow-up visit, and the last image (D) at the 4-year follow-up visit.

Figure 12. Spitz nevus.

The starburst pattern is the most common pattern manifest by typical pigmented Spitz nevi.

Figure 13. Evolving Spitz nevus.

At baseline this nevus revealed a starburst pattern. The lesion was re-imaged at a 6-month follow-up appointment and another image was obtained at 2-year follow-up. The starburst pattern had transformed into a homogeneous pattern.

Figure 14. Spitz nevus by view of polarized and nonpolarized dermoscopy.

A focal area with a negative network is visible on nonpolarized dermoscopy (A) and polarized dermoscopy (B). The negative network is located on the right side of the lesion at approximately 3 o’clock.

Figure 15. Chrysalis structures.

These fine, white streaks are only visualized with polarized dermoscopy (B) and are not visible with nonpolarized dermoscopy (A).

Figure 16. Atypical nevoid lesion.

This asymmetric pigmented lesion reveals focal pseudopods, irregular blue–white veil and atypical network. This constellation of findings raises concern for melanoma. The lesion was excised and the histopathology was deemed to be consistent with a Spitz nevus.

Figure 17. Superficial spreading melanoma.

These lesions often manifest the clinical ABCD features of melanoma, and under dermoscopy they often display some of the structures listed in Table 3 that heighten the suspicion of melanoma. This particular lesion has atypical dots and globules, irregular network with branched streaks and an irregular blotch. Superficial spreading melanomas are not commonly found in children.

Figure 18. Amelanotic melanoma.

This lesion developed over a few months on the cheek of a 17-year-old. No ABCD features were present on clinical examination. However, under dermoscopy irregular blood vessels are visualized, which helps to correctly diagnose the lesion as a cutaneous malignancy.

Figure 19. Nodular melanoma.

This lesion lacks clinical ABCD features; however, it does reveal irregular serpentine blood vessels, which are melanoma predictive structures, as noted in Table 3.

Melanocytic neoplasms of childhood belong to three distinct classes, including congenital nevi, acquired nevi and melanoma. Congenital melanocytic nevi (CMN) consist of nevi that are clinically evident at birth, as well as nevi manifesting congenital features that become clinically apparent shortly after birth (i.e., tardive CMN) [1]. In addition, nevus spilus and segmental speckled-lentiginous nevus are also considered to be CMN. Melanocytic nevi that develop many months to years after birth are termed acquired melanocytic nevi (AMN) and include junctional nevi, compound nevi, dermal nevi, blue nevi (BN) and Spitz nevi (SN). Although rare, the incidence of melanoma in the pediatric population appears to be rising, and as such, it has become imperative that clinicians include melanoma in the differential diagnosis of atypical pigmented or amelanotic lesions in children [2–4]. It is important to acknowledge that melanoma can develop in healthy children, as well as those with underlying genetic or immunologic disorders, such as xeroderma pigmentosum. Approximately half of all pediatric melanomas arise in a de novo fashion, while the other 50% emerge in association with pre-existing cutaneous lesions. Nearly 30% of childhood melanomas arise within giant CMN, and approximately 20% develop in association with AMN [5]. Thus, any suspicious or evolving lesion in a child should not be dismissed as a benign entity, and a diagnosis of melanoma ought to enter the differential.

The clinical features of melanoma in children can be quite subtle, and can mimic SN and angiomas, often resulting in missed opportunities to perform a diagnostic biopsy in a timely fashion. Interestingly, retrospective studies suggest that at the time of diagnosis, up to 60% of pediatric melanomas are of intermediate thickness, which may in part be due to a delay in the clinical diagnosis and hesitation on the part of the clinician to perform a biopsy [6,7]. On the other hand, many benign CMN and AMN can manifest clinical features resembling melanoma, prompting unnecessary biopsies. It goes without saying that any technique that increases the sensitivity for detecting melanoma, while at the same time improving specificity, would be highly valued by clinicians. One technique that can improve a physician’s ability to detect melanoma and avoid superfluous biopsies in both children and adults is dermoscopy.

A dermatoscope is a noninvasive, hand-held tool that allows for the visualization of morphologic structures within pigmented skin lesions (Table 1). The presence or absence of certain structures and colors, and their relative distribution within a lesion, can be used to guide management decisions, including whether or not to perform a biopsy. The utility of dermoscopy is exemplified by the ability to correctly identify benign SN, which often clinically resemble malignant melanoma. The diagnostic accuracy of SN increases from 56% with naked eye examination to 93% with the aid of dermoscopy [8,9]. Given that surgical excision was previously the only option available to closely evaluate atypical cutaneous lesions, the benefit of noninvasive dermoscopy is incontrovertible. Examination of nevi with serial dermoscopic evaluations in addition to sequential clinical monitoring decreases the need for surgical removal of suspicious lesions from 15.6 to 9%, when compared with unaided visual assessment alone [10].

Two dermoscopic devices and methods of examining skin lesions exist, and include nonpolarized and polarized dermoscopy. In the case of nonpolarized dermoscopy, oil, alcohol or water is applied to the skin to create a liquid interface, and the lens of the dermatoscope comes in direct contact with the patient’s skin. Polarized dermatoscopes, on the other hand, do not require instrument-to-skin contact or an immersion liquid for visualization of subsurface morphology. As such, polarized dermoscopy is the method of choice when examining apprehensive children who tend to resist the physical contact involved in nonpolarized dermoscopic examinations.

In this article, we discuss prominent clinical and dermoscopic features across the spectrum of melanocytic lesions in children, and underscore the value of dermoscopy in the diagnosis of nevi and melanoma in the pediatric population.

Melanocytic nevi & melanoma

Congenital melanocytic nevi

Congenital nevi are likely the result of aberrant melanocyte migration, differentiation and deposition in the dermis during the early stages of embryogenesis [11]. CMN are classified by size relative to the greatest diameter that they are expected to attain during adulthood. They are categorized into small (<1.5 cm), medium (1.5–19.9 cm), large (>20 cm) and very large or giant ‘garment’ nevi (>40–60 cm) [12]. CMN have the tendency to enlarge in proportion to the growth of the child and may additionally develop changes in color and surface topography over time [13,14]. Although the absolute risk for developing melanoma in association with CMN is low, the relative risk is high, and is more significant for larger CMN than for smaller CMN [15]. Thus, it is important to scrutinize these lesions for focal changes that may herald the development of melanoma.

On clinical examination, CMN appear as flat to elevated, light to dark brown lesions with variable shades of pigmentation and irregular borders. The surface topography ranges from smooth to mammillated to cribriform, and coarse terminal hairs may protrude from the lesion, which becomes most prominent during puberty [16]. Nearly 75% of patients with large CMN have satellite nevi; however, these satellite nevi do not appear to carry an increased risk for developing cutaneous melanoma [17]. Dermoscopic assessment of the subsurface morphology of CMN and associated satellite lesions with attention to recognizable benign patterns is beneficial in distinguishing CMN from melanoma, and in identifying a focus of melanoma arising along the dermo–epidermal junction within a CMN [15,17]. Most CMN, especially smaller lesions, manifest a symmetric, organized pattern on clinical and dermoscopic evaluation. That being said, it is not uncommon to encounter CMN with a disorganized pattern under dermoscopy, and in such cases it may be difficult to exclude melanoma from the diagnosis without performing a biopsy to definitively rule out malignancy (Figures 1 & 2).

The predominant dermoscopic patterns in CMN are diffuse reticular, patchy reticular, globular, peripheral reticular with central globules (reticular-globular) and homogeneous (Table 2 & Figure 3). The type of dermoscopic pattern manifested in a CMN is related in large part to the anatomical location of the nevus. Most CMN located on the lower extremities exhibit a reticular pattern, on the head and neck a globular pattern, and the majority of CMN on the torso manifest a globular or reticular-globular pattern [18,19]. The reticular network in CMN are defined by their quality, distribution and some unique traits that are specific to CMN. The lines of the network can be thin or thick in quality. The distribution of the reticulation most commonly extends throughout the lesion (Figure 4), but may be focally present within the lesion or localized to the periphery (Figures 1 & 2). Furthermore, the pigment network can appear as thickened linear network fragments or branched streaks resembling fungal hyphae. Observing the aforementioned patterns under dermoscopy in the absence of dermoscopic features that are concerning for malignancy (Table 3) greatly increases the likelihood that a lesion is a CMN and not a melanoma.

As previously mentioned, most CMN on the head, neck and trunk have a globular component [20]. The quality, distribution and specific types of globules within CMN are important to note. Globules are delineated as small or large in size, and when the globules are large in size, angulated in shape and crowded back-to-back within the lesion, they are described as having a ‘cobblestone’ pattern (Figure 5)[21]. In addition, it is common to see small globules centered within the hole of the network in CMN; this particular configuration of globules is called target network with globules or target globules (Figure 6)[22]. The relative distribution of globules within nevi is variable, although common patterns include sparse distribution throughout the lesion, dense aggregates throughout the lesion and central clustering surrounded by reticulation. Additional unique dermoscopic structures commonly visualized in CMN include small milia-like cysts, perifollicular pigment changes and various types of blood vessels [23,24].

Congenital melanocytic nevi that deviate from the patterns described above, exhibit dermoscopic features that are commonly observed in melanoma (Table 3), reveal an asymmetric or multicomponent pattern, or exhibit a rapid growth should be viewed with caution, and melanoma should enter the differential diagnosis (Figure 7). It is important to note that despite parental concerns regarding the increased relative risk of malignant transformation within a CMN, there is no data to suggest that the prophylactic removal of these lesions lowers the incidence of melanoma [25]. With that being said, absence of evidence is not evidence of absence. It should be intuitively obvious that complete surgical removal of a CMN will prevent the development of melanomas that may have been destined to arise within that CMN. Furthermore, if psychosocial or cosmetic concerns become paramount, surgical excision, dermabrasion, curettage or laser therapy may be entertained to improve cosmetic and functional outcomes with varying levels of patient satisfaction [26]. For patients at an increased risk for developing melanoma, periodic clinical monitoring with serial photographic and dermoscopic evaluation is essential to screen for changes that would reflect malignant transformation.

Nevus spilus (speckled lentiginous nevus)

Nevus spilus is purported to be a subtype of CMN that initially presents as a well-delineated hyperpigmented patch or café au lait macule that later develops a characteristic, superimposed speckling pattern [27,28]. The lesions are clinically asymptomatic and expand in size in proportion to the growth of the affected child. In some cases, speckled lentiginous nevus (SPLN) have a relatively small diameter, but the nevus can in fact involve a large portion of the body surface area. Monitoring of SPLN in a clinical and dermoscopic manner provides information about any variations in morphology that would be indicative of melanoma.

Two subtypes of nevus spilus have been reported in the literature and include the macular variant, nevus spilus maculosus, and the papular variant, nevus spilus papulosus [29,30]. The macular type is characterized by evenly distributed, flat, dark speckles within a large, well-circumscribed, light brown patch. The papular type, on the other hand, consists of a well-circumscribed lentiginous patch that is studded with multiple raised papules. Histologic evaluation of the speckled component in the papular form demonstrates dermal or compound melanocytic nests, whereas in the macular type the melanocytes are predominantly junctional. Both macular and papular SPLN are associated with an increased probability of developing SN, which must be distinguished from melanoma [29]. Interestingly, the risk of developing cutaneous melanoma within a SPLN appears to be greater for those exhibiting the macular subtype (25 vs 10%) [29].

Nevus spilus has been likened to a ‘melanocytic garden’ in which BN, SN, junctional nevi, compound nevi, intradermal nevi and melanoma can arise [27,31]. Given the reported association of melanoma arising within a nevus spilus, periodic clinical monitoring and dermoscopic evaluation seems reasonable [32]. Under dermoscopy, the background of a benign nevus spilus appears homogeneous tan in color and may exhibit a faint, delicate network. Hyperpigmented macules or papules within a SPLN generally show dermoscopic features that correlate with the type of nevus present (refer to the ‘Acquired melanocytic nevi’ section below) [33]. Utilizing dermoscopy facilitates ongoing supervision of such lesions and minimizes unnecessary surgical procedures in children [34].

Acquired melanocytic nevi

Acquired melanocytic nevi are benign proliferations of melanocytes, and both genetic and environmental factors have been associated with the development of acquired nevi [35,36]. On clinical examination, AMN typically measure less than 6 mm in diameter and have a homogeneous tan to brown color, with a smooth surface topography [37]. AMN are classified histologically into three groups: junctional nevi; compound nevi; and intradermal nevi.

Most acquired nevi exhibit one of ten symmetric and organized dermoscopic patterns (Figure 3). Typical patterns observed in acquired nevi include: diffuse or patchy network; peripheral reticulation with central hypo- or hyper-pigmentation; homogeneous tan/pink/brown or blue pigmentation; peripheral network with central globules; peripheral globular or starburst; globular; two-component; and symmetric multicomponent [38,39]. In general, most individuals manifest a predominant nevus pattern, which is defined as the nevus pattern configuration in more than 30% of their nevi [40]. The prevalent nevus pattern depends to some degree on the age and skin type of the individual. Children of less than 10 years of age classically have globular or homogeneous patterned nevi, whereas adults generally display reticulated nevi [41]. Individuals with Fitzpatrick skin type I (fair complexion) have a predominant nevus pattern typified by light brown coloration with central hypopigmentation (Figure 8), types II and III have light to dark brown nevi with multifocal pigmentation, and type IV individuals (dark complexion) classically have black or dark brown nevi with central hyperpigmentation (Figure 9)[40]. Visualization of a predominant nevus pattern can help identify those individuals who are at an increased risk for developing melanoma, and aid in the detection of ‘ugly duckling’ outlier lesions that may represent malignancy [42,43].

A reported dermoscopic finding in some AMN is the presence of peripheral globules around the entire perimeter of the nevus (Figure 10). This pattern signifies active growth of the nevus, and therefore it can be predicted that such lesions will symmetrically enlarge over time. Once these nevi enter senescence, they manifest a reticular or homogeneous pattern, and the peripheral globules tend to diminish in size until they eventually disappear from sight [44]. From a management perspective, it is reassuring to know that symmetrically enlarging acquired nevi manifesting a peripheral rim of globules do not need to be subjected to biopsy and can be confidently monitored clinically and dermoscopically in children and young adults.

Although the ABCD mnemonic (asymmetry, border irregularity, color variation and diameter >6 mm) can assist in differentiating benign melanocytic nevi from melanoma, it is clear that the criteria lacks specificity since many melanocytic nevi, especially dysplastic nevi, can manifest the ABCDs or can enlarge over time [45,46]. For that reason, one should not assume that all evolving melanocytic lesions in children represent melanoma. In the Framingham study, 76% of children were noted to develop new nevi, 29% had regressing nevi, 34% had enlarging nevi and as many as 50% of AMN had dermoscopic variation from baseline when viewed at a 3-year follow-up visit [47]. It is essential to appreciate that changing lesions that maintain the benign patterns listed in Table 2 and are not otherwise suspicious for malignancy do not require excision.

In the literature, the perception of a structureless blue area has been described on dermoscopic evaluation of some AMN, including BN, combined nevi and compound and intradermal nevi [48]. AMN with melanin pigment in the dermis, either in melanophages or pigmented melanocytes, will exhibit a blue hue when viewed dermoscopically [49]. A direct contrast must be made with the ‘blue–white veil’ that is associated with melanoma and consists of an irregular structureless area with blue pigment with an overlying ‘ground glass’ hazy appearance [50,51]. The faint blue hue noted within some melanocytic nevi may simulate the blue–white veil perceived in melanoma, and such lesions should be closely monitored or biopsied to definitively rule out malignancy.

Blue nevi

Blue nevi are rarely present at birth, and tend to emerge during childhood and adolescence. BN represent benign proliferations of dermal dendritic melanocytes; likely an aberrant, premature arrest of migrating melanocytes in the dermis during fetal development. A BN appears clinically as a small, smooth-surfaced, blue papule on the head, neck, distal extremities or buttocks. Various classes of BN have been described, and include black–blue nevi, cellular BN, sclerosing BN and polychromatic BN [52]. Cellular BN are benign neoplasms that are large, blue–black lesions measuring 1–3 cm in diameter [53]. Epitheliod BN are a histologic subtype of nevi that are associated with the Carney complex in children, encompassing a triad of cardiac myxomas, skin hyperpigmentation and endocrine overactivity [54]. As a general rule, BN are benign in children; however, on exceedingly rare ocassions, a large, evolving, blue–black plaque may represent a primary or metastatic melanoma (‘malignant blue nevus’) [55–57].

The dermoscopic features of BN vary when lesions are observed with nonpolarized and polarized light dermoscopy. In general, nonpolarized dermoscopy allows clinicians to diagnose a blue nevus with greater confidence than polarized dermoscopy, owning to the more homogeneous blue hue visualized under a nonpolarized light source [58]. Dermoscopically, BN appear as symmetrical, sharply defined lesions displaying a uniformly homogenous steel-blue color [59]. Arising as solitary lesions, BN may be concerning on visual inspection; however, the absence of any melanoma-associated structures (Table 3) and the presence of homogeneity on dermoscopic evaluation are reassuring characteristics of a BN [60]. Any evidence of dermoscopic heterogeneity or the presence of a network, globules, vessels or chrysalis structures should raise suspicion for melanoma; however, even these lesions usually prove to be sclerosing BN or combined nevi (congenital nevus with several populations of melanocytes) on histopathologic evaluation.

Halo nevi (Sutton’s nevi, leukoderma acquisitum centrifugum)

Halo nevi (HN) are benign melanocytic nevi, mainly compound or dermal type, that are encircled by a zone of depigmentation [61]. These nevi are common in the pediatric population, and it is not uncommon for affected individuals to have multiple HN on the body [62]. It has been hypothesized that HN undergo spontaneous involution by a T-cell-mediated immune response over time, and may even fully disappear by adulthood [63]. Once the regression of the central nevus is complete, the area of previous depigmentation tends to repigment to the color of the surrounding skin. Although HN are benign, on very rare occasions regressing melanomas may mimic HN [64]. In addition, although infrequently, a regressing melanoma can lead to the sudden transformation of existing nevi into HN [65–67]. Thus, patients presenting with many eruptive HN should be examined carefully to ensure that they do not have an undiagnosed melanoma somewhere on their skin.

Dermoscopic evaluation of a HN typically reveals a globular or homogeneous pattern in the central pigmented portion of the lesion, delimited by a halo of depigmentation (Figure 11)[68]. The melanocytic nevus within the halo reduces in size during the regression process and eventually disappears (Figure 11)[69]. Following regression, a tan to pink central region with dotted vessels may be observed in place of the nevus. Continued monitoring of HN usually reveals a decrease in halo diameter over time, eventuating in the replacement of the depigmented area with normal-appearing skin color. Excision of HN in children should only be contemplated if the dermoscopic features vary from the aforementioned benign patterns (Figure 3), if the halo is irregular (i.e., asymmetrical) or if the depigmented area reveals melanoma concerning structures, such as extensive peppering or a blue–white veil (Table 3).

Spitz nevus

Spitz nevi are dome-shaped, pink to brown papules that often arise on the head, neck and extremities in children [70]. The lesions generally measure less than 1 cm in diameter, but may grow over time and change color, raising concern for melanoma [71]. In the past, SN were histopathologically mistaken for melanoma due to overlapping microscopic features, but are now accepted as a benign entity when appropriately diagnosed [72,73]. The differential diagnosis of SN is broad, and includes Clark’s nevus, pyogenic granuloma, hemangioma, juvenile xanthogranuloma and melanoma.

The diagnosic accuracy of SN has increased from 56 to 93% with the use of dermoscopy [8]. Differentiating melanoma from SN is less complicated when dermoscopic patterns are recognized and appreciated during clinical examination. The most common patterns seen in SN are starburst, thick reticular network, globular, homogeneous pink, homogeneous black lamella, negative pigment network and atypical or multicomponent pattern [74]. In addition, it is not uncommon to see chrysalis structures within SN [75,76]. Of the abovementioned patterns, the most commonly encountered type is the starburst pattern, which appears in over 50% of SN (Figure 12)[77]. SN with a starburst pattern often have a blue-gray to brown-black center that is surrounded by multiple rows of globules or streaks/pseudopods arranged in a radial pattern at the periphery. When this characteristic starburst pattern is encountered, there is a diagnostic sensitivity of 96% for SN [78]. Sequential dermoscopic monitoring of a classic starburst patterned SN will likely reveal symmetric growth of the lesion followed by the transformation of the starburst pattern into a homogeneous pattern (Figure 13)[79,80].

A negative network pattern, in the presence or absence of chrysalis-like structures, is another frequently observed characteristic of SN [81]. The negative network, which can be visualized with both polarized and nonpolarized dermoscopy, appears as light areas delineating the grid and dark regions representing the holes. Another way to envision a negative network is that the darker structures are irregular, elongated, curvilinear globules surrounded by relative hypopigmentation (Figure 14A & B). In counter distinction, a chrysalis structure consists of shiny, bright white lines that likely correspond to dermal collagen, which due to its birefringent properties, is easily visible using polarized light dermoscopy (Figure 15A & B). Negative network and chrysalis structures are not commonly encountered in melanocytic lesions, but when both are visualized, a diagnosis of SN versus melanoma is favored [75].

Besides the prototypes mentioned above, SN can also present with a homogeneous dark and thickened network pattern [82]. Globular patterned SN are noted in as many as 22% of lesions, and consist of regularly distributed globules or irregular globular aggregates of varying size and color [74]. In addition, peripherally located globules, giving a starburst-like appearance, can also be detected [83]. Dermoscopic structures are rarely visualized in homogeneous black-lamella type SN; however, in the homogeneous pink variant, it is common to observe dotted blood vessels within the lesion. These pink, vascular lesions can resemble amelanotic melanoma on clinical and dermoscopic examination [84]. SN can also present with an asymmetric or disorganized pattern. Such lesions may exhibit a multicomponent pattern or eccentric hyperpigmentation and, unfortunately, are impossible to differentiate from melanoma on clinical examination (Figure 16)[85,86].

The management of SN remains challenging given the risk of failure to differentiate a benign SN from a malignant neoplasm [87]. The decision to excise a presumed SN in lieu of clinical monitoring is dependent on a host of factors, such as the clinical findings, dermoscopic findings, history and anxiety of the physician and/or patient/family, just to mention a few.

Melanoma

Approximately 2% of melanomas appear in individuals less than 20 years of age, and as such, the diagnosis of melanoma during childhood is not often entertained in the differential diagnosis [4,88,89]. Although the symptoms and risk factors associated with melanoma in children parallel those in adults, a higher percentage of amelanotic and nodular melanomas are diagnosed in the pediatric population when compared with adults [6]. These melanomas often lack the ABCD features commonly associated with superficial spreading melanoma, rendering the early detection of such lesions challenging. In other words, physicians often fail to include melanoma in the differential diagnosis of atypical lesions in children, resulting in significant delays in arriving at an accurate diagnosis. Confounding the problem of diagnostic delay is the reluctance by many physicians to subject children to a skin biopsy [90].

Melanomas usually manifest an asymmetric dermoscopic pattern, or a pattern that deviates from the benign prototypes shown in Figure 3[91,92]. In addition, melanomas tend to contain at least one of the ten dermoscopic structures listed in Table 3[93]. In other words, melanocytic lesions with organized and/or symmetric dermoscopic structures that display the benign dermoscopic patterns outlined in Table 2 have an exceedingly low probability of being diagnosed as cutaneous melanoma. Any lesion that exhibits global patterns, specific structures or colors that deviate from the benign classifications noted in Table 2 should be closely evaluated for attributes of malignancy (Table 3).

The most common histopathologic subtypes of melanoma diagnosed in children are superficial spreading melanoma and nodular melanoma [94]. Superficial spreading melanomas generally grow slowly and manifest one or more of the structures outlined in (Table 3 & Figure 17). In comparison, nodular melanomas are often amelanotic and tend to grow rapidly, and the appreciation of atypical vascular structures on dermoscopy is of great value in diagnosing these melanomas (Figures 18 & 19). Malignant melanoma should enter the differential diagnosis of any nodular pink lesion exhibiting dotted vessels, irregular linear vessels or serpentine vessels, especially if the lesion is firm and rapidly growing [60,95]. The fact that a patient is young should never preclude a physician from obtaining a biopsy if there is an index of suspicion for melanoma.

Expert commentary

The evaluation of melanocytic neoplasms in children is important given the rising incidence of melanoma in the pediatric population. The use of dermoscopy can facilitate in diagnosing melanomas while these tumors are still thin and treatment modalities generally have positive outcomes. A multifaceted approach increases the sensitivity and specificity for diagnosing melanoma, and includes a thorough clinical history, visual examination and routine dermoscopic evaluation of suspicious skin lesions. A recent meta-analysis demonstrated that the diagnostic accuracy of melanoma improved 49% with the use of dermoscopy [96]. Although there is overwhelming evidence for the benefits of using dermoscopy, it is only utilized by approximately 20–25% of dermatologists in the USA [96]. Thus, there remains a great need to encourage the diffusion of dermoscopy into the clinical practice.

Dermoscopy gives clinicians the ability to visualize subsurface colors, structures and patterns in skin neoplasms, which in turn leads to more accurate clinical diagnoses of cutaneous lesions and the implementation of appropriate management techniques. In the case of nevi that simulate melanoma on naked-eye visual examination, dermoscopy often provides a view of reassuring morphologic features that call for continued clinical monitoring, rather than surgical excision. Serial dermoscopy is especially beneficial in the monitoring of patients with CMN or in patients with familial atypical multiple mole-melanoma syndrome or atypical mole syndrome. The decision of whether to observe a clinically atypical lesion or to perform a biopsy can often be made with improved confidence based on the presence or absence of various features observed on dermoscopic evaluation. In addition, use of dermoscopy also has the potential to enhance patient and parental confidence in the diagnosis and management recommendations provided by the physician.

Five-year view

Increased efforts to improve physician awareness regarding the benefits of using dermoscopy remain paramount. Towards that end, continued dissemination of information regarding the benign and malignant dermoscopic features of lesions should prove to be a valuable endeavor. In addition, evidence-based literature suggests that dermoscopy is most beneficial in the hands of well-trained physicians, and as such, much still needs to be done to facilitate the integration of dermoscopy training into medical practice, residency programs and perhaps even medical school teachings. Although dermoscopy was only utilized by dermatologists in the early phases of its development, many family physicians are starting to eagerly engage in learning and implementing its use in clinical practice. We have previously published on the potential utility of dermoscopy for the pathologist [97] and are currently investigating the feasibility of introducing dermoscopy to medical students who are starting their clinical skills curriculum. Another intriguing development is the recent observation that some high-risk patients have started purchasing their own dermatoscopes to assist them in their self-skin examination efforts. Thus, it is plausible that the dermatoscope will be in the hands of not just dermatologists, but the hands of many different types of healthcare providers and motivated patients over the next 5 years.

A better understanding of the utility of dermoscopy combined with improved training programs is likely to transform dermoscopy into a widely used tool, akin to the stethoscope, among primary care physicians, medical specialists and those in medical training. The dissemination of dermoscopy among medical professionals will likely have great impact on the early detection of melanoma, translating into lives saved from this potentially fatal malignancy. Dermoscopy seeks to gain a special place in the detection and monitoring of melanocytic neoplasms in children, as the technique assuredly helps guide physicians as to whether or not surgical interventions are necessary. Without a doubt, the ease with which nevoid lesions can be evaluated is enhanced with dermoscopy.

Table 1. Dermoscopic structures and their histopathological correlates.

Dermoscopic structures	Definition	Histopathological correlation
Pigment network (reticulation)	Grid-like network consisting of brown or black pigmented ‘lines’ and hypopigmented ‘holes’	Melanin in keratinocytes and/or melanocytes along the epidermal rete ridges
Pseudonetwork	In facial lesions, diffuse pigmentation interrupted by nonpigmented follicular openings, appearing similar to a network	Pigment in the epidermis or dermis interrupted by follicular and adnexal openings of the face
Structureless (homogenous) areas	Areas devoid of dermoscopic structures and without regression. These areas can be pigmented or hypo-pigmented. In other words, these areas can have the same color as the background skin or slightly darker than background skin, but lighter than the predominant color of the nevus. If the area is uniformly dark, it is referred to as a ‘blotch’ instead of as a structureless area (see below)	Relative decrease in the concentration of melanin and/or fattening of the dermo–epidermal junction
Dots	Small, round structures less than 0.1 mm in diameter that may be black, brown, gray or bluish	Aggregates of melanocytes or melanin granules. Black dots represent pigment in the upper epidermis or stratum corneum. Brown dots represent pigment at the dermo–epidermal junction or in the epidermis. Gray–blue dots represent pigment in the papillary dermis
Peppering	Tiny, blue-gray granules	Melanin deposited as intracellular (mostly within melanophages) or extracellular particles in the upper dermis
Globules	Aggregated sharply circumscribed round to oval structures that may be brown, black or blue in color with diameters measuring greater than 0.1 mm	Nests of melanocytes
Streaks (pseudopods, radial streaming)	Radially arranged, projections of dark pigment (brown to black) at the periphery of the lesion	Confluent junctional nests of melanocytes
Blotches	Dark brown to black, usually homogenous areas of pigment that obscure the ability to visualize underlying structures	Aggregates of melanin in the stratum corneum, epidermis and upper dermis
Regression areas	White, scar-like depigmentation (lighter than the surrounding skin, shiny white under polarized dermoscopy) often combined with or adjacent to blue–gray areas or peppering	Scar-like changes: fibrotic papillary dermis, sparse lymphocytic infiltrates and variable numbers of melanophages
Blue–white veil	Irregular, confluent blue pigmentation with an overlying white ‘ground glass’ haze	Aggregation of heavily pigmented cells (usually melanoma cells and/or melanophages) in the dermis in combination with compact orthokeratosis of the stratum corneum
Vascular pattern	Milky red areas, dotted, globular, linear, comma, serpentine or twisted red structures with differing sizes	Tumor neoangiogenesis and dilated blood vessels in the papillary dermis (‘vascular blush’)
Milia-like cysts	Round whitish or yellowish structures that shine brightly (like ‘stars in the sky’) under nonpolarized dermoscopy	Intraepidermal keratin cysts
Comedo-like openings	‘Blackhead’-like plugs on the surface of the lesion	Concave clefts in the surface of the epidermis, often filled with keratin
Fingerprint-like structures	Thin, light brown parallel lines	Probably represent thin, elongated pigmented epidermal ridges
Ridges (gyri) and fissures (sulci)	Cerebriform surface resulting in gyri (ridges) and sulci (fissures). Confluence of adjacent comedo-like openings will create a fissure (sulcus) or crypts	Keratin filled invaginations on the skin surface
Moth-eaten border	Concave invaginations of the lesion border
Leaf-like areas	Brown to gray-blue discrete bulbous structures resembling a leaf pattern	Pigmented basal cell tumor islands
Spoke-wheel-like structures	Well-circumscribed brown to gray-blue-brown radial projections meeting at a darker brown central hub	Nests of basal cell carcinoma radiating from the follicular epithelium
Large blue-gray ovoid nests	Large, well-circumscribed areas, that are more sizeable than globules	Large nests of basal cell tumor in the dermis
Multiple blue-gray globules	Round, well-circumscribed nonaggregated structures, which in the absence of a pigment network, suggest basal cell carcinoma	Small nests of basal cell tumor in the dermis
Lacunae	Red, maroon or black lagoons	Dilated vascular spaces
Parallel patterns	On the palms and soles, parallel rows of pigmentation following the furrows (nevi) or ridges (melanoma) of the dermatoglyphics	Pigmented melanocytes in the furrows (crista limitants) or ridges (crista intermedia) of acral skin

Table 2. Benign dermoscopic patterns.

Global pattern	Definition
Reticular diffuse	Diffuse network with uniform thickness and color of lines. The holes of the network are of relatively uniform size. The network tends to fade at the periphery. This pattern can be seen in congenital nevi, especially those located on the lower extremity, and in acquired nevi
Reticular patchy	Network with uniform thickness and color of lines. However, the network is not contiguous and is interrupted by the presence of homogeneous structureless areas. This pattern can be seen in congenital nevi, especially those located on the lower extremity, and in acquired nevi
Peripheral reticular with central hypopigmentation	A relatively uniform network at the periphery of the lesion with a central homogeneous and hypopigmented structureless area. This type of acquired nevus is more common in fair skinned individuals
Peripheral reticular with central hyperpigmentation	A relatively uniform network at the periphery of the lesion with a central homogeneous and hyperpigmented blotch. This type of acquired nevus is more common in darker skinned individuals
Globular	Globules of similar shape, size and color distributed symmetrically throughout the lesion. This pattern is seen most commonly in congenital nevi
Peripheral reticular with central globules	A relatively uniform network at the periphery of the lesion with a central globules. This pattern is seen most often in nevi with a congenital histopathology pattern
Peripheral globules with central network or homogeneous area	The central component of the this type of nevus is either reticular or homogeneous. Relatively uniform globules surround the entire perimeter of the lesion. This represents an acquired growing nevus that has not yet undergone senescence
Starburst	Streaks (radial streaming or pseudopods) present around the perimeter of the lesion giving the appearance of an exploding star
Homogeneous tan, brown or blue pigmentation	Primarily diffuse structureless pattern with or without reticular networks fragments and/or remnant globules. When tan in color they usually represent acquired nevi in fair skin phenotypes. When brown in color they usually represent congenital nevi. When blue in color they represent blue nevi
Two component	These lesions reveal two different patterns (reticular-globular, reticular-homogeneous or globular-homogeneous). Half of the lesion manifests one pattern, while the other half of the lesion manifests a different pattern
Multicomponent	Symmetrically distributed globules, reticulation, blotches, dots, veil, regression structures and/or structureless areas (three or more of these need to be present)

NB: The term network and reticulation are used interchangeably throughout the manuscript.

Table 3. Histopathologic correlates of dermoscopic structures indicative of melanoma.

Dermoscopic structure	Description	Histopathologic correlate
Atypical pigment network	Reticulated grid of brown lines with broadened, thickened or darkened areas that may end abruptly at the periphery	Atypical lentiginous or nested melanocytic proliferation along the dermo–epidermal junction
Streaks	Linear, radially oriented pigmented projections at the periphery of a lesion	Confluent junctional nests of pigmented melanoma cells at the periphery (radial growth phase)
Negative pigment network	The ‘negative’ of the pigment network, consisting of hypopigmented lines making up the grid, and dark areas filling up the ‘holes’	Thin elongated rete ridges and large tubular melanocytic nests within a widened papillary dermis. May also correspond to bridging of adjacent rete ridges
Chrysalis	Fine, bright white, shiny streaks oriented in an orthogonal fashion within a lesion, visible only under polarized light dermoscopy	Remodeled or new papillary dermal collagen
Atypical dots and globules	Dark, punctate or round to oval structures of varying shape, size, color and distribution within a lesion	Junctional or dermal nests of melanocytes; dots can also represent pagetoid nests
Irregular blotches	Dark areas of diffuse pigmentation with irregular shapes, sharp margins or eccentric locations	Melanin pigmentation throughout the epidermis or dermis or both
Blue–white structures over raised areas	White areas, blue areas or both, overlying raised or thick portions of a lesion	Compact orthokeratosis overlying melanophages, melanocytes or free melanin in the papillary dermis
Blue–white structures over flat areas (also known as regression structures)	White areas, blue areas or both, overlying flat or thin portions of a lesion	Fibrosis within the papillary dermis and melanosis (melanophages and free melanin ‘dust’ within the dermis)
Atypical vascular structures	Milky red areas, dotted, linear, serpentine or twisted red structures with differing sizes	Tumor-induced angiogenesis
Peripheral brown structureless areas	Peripherally arranged light brown or tan areas of variable shape lacking perceptible structures	Flattening of the rete ridges with pagetoid spread of atypical melanocytes

Key issues

• • Children present to pediatricians and dermatologists with a variety of melanocytic lesions, ranging from congenital nevi to acquired nevi to melanoma.

• • Dermoscopy is a tool that improves the physician’s ability to diagnose melanoma and to differentiate benign nevi from melanoma.

• • Knowledge of the dermoscopic colors, patterns and structures of benign versus malignant lesions is imperative for the physician using dermoscopy.

• • Dermoscopy can guide management decisions regarding whether or not to biopsy or excise a clinically atypical or suspicious pigmented lesion.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Dermoscopy of nevi and melanoma in childhood

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Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

1. Which of the following statements about the potential advantages and disadvantages of dermoscopy of melanocytic lesions in children is correct?

• □ A Dermoscopy is invasive

• □ B Dermoscopy allows for the visualization of subsurface colors and structures within pigmented melanocytic skin lesions

• □ C Dermoscopy is not helpful in diagnosing melanomas until the tumors have advanced thickness

• □ D Dermoscopy is used by most US dermatologists

2. Your patient is a 3-year-old, white girl with a suspicious melanocytic lesion on her forearm. Which of the following features seen on dermoscopy is most likely to indicate that the lesion is benign?

• □ A Reticular diffuse global pattern

• □ B Negative pigment network

• □ C Streaks

• □ D Blue–white structures over flat areas

3. Dermoscopy on the patient in question 2 suggests that the lesion is a melanoma. Which of the following statements is most likely to apply to her work-up and management?

• □ A Dermoscopy improves diagnostic accuracy for melanoma by 15% over clinical evaluation alone

• □ B Chrysalis can be visualized without polarized light

• □ C Observation or serial dermoscopy is preferred over biopsy

• □ D Superficial spreading melanoma and nodular melanoma are the most common histopathologic subtypes of melanoma diagnosed in children

4. Which of the following statements about melanocytic neoplasms of childhood is correct?

• □ A There are 5 distinct classes of melanocytic neoplasms of childhood

• □ B Nevus spilus is an acquired melanocytic nevus (AMN)

• □ C Spitz nevi are congenital melanocytic nevi (CMN)

• □ D Melanoma should be included in the differential diagnosis of atypical pigmented or amelanotic lesions in healthy children