Key points

Introduction

Pediatric melanoma is extremely rare, especially before puberty. During the last congress of the American Academy of Dermatology, a famous pediatric dermatologist compared childhood melanoma to the legend of “Bigfoot,” a figure everybody is concerned about, but that only a few actually declare to have seen in their life. Of course she was not questioning the existence of childhood melanoma, but wanted to point the accent on the extreme rarity of this event and on the fact that, because of its rarity, no clear-cut clinical features and patterns of presentation are actually known. Most physicians will probably never be confronted with this malignancy, but even if they do encounter it, they might not readily recognize it. Recent findings in fact corroborated previous studies indicating that childhood melanoma does not present with conventional ABCDE criteria for melanoma. Most frequently it may mimic clinically nonmelanocytic lesions, such as angioma, pyogenic granuloma, viral wart, and molluscum. The same lesions are in the differential diagnosis of amelanotic/hypomelanotic Spitz nevi, which actually represent the main clinically and histopathologically challenging lesions to be differentiated from melanoma in this age group. In this scenario, it is not surprising that accuracy in melanoma detection in children still remains low. A recent study tested the accuracy in melanoma detection in children and adolescents over a 10-year period, using the NNE value (number needed to excise; obtained dividing the total number of excised lesions by the number of melanomas). The NNE value for this pediatric population (0–18 years) was 20 times higher than the rates usually found in adult patients, meaning that a very high number of benign nevi (ie, approximately 594) were excised to detect one melanoma. An effective strategy to reduce the number of unnecessary excisions would be to focus on problematic lesions. Epidemiologic data indicate that, apart from immune suppression and genetic conditions (such as xeroderma pigmentosum), the main risk factor for developing melanoma in a pediatric population is represented by the presence of a large congenital nevus. Thus, spitzoid lesions and congenital nevi have to be considered the true problematic lesions in children, representing melanoma simulator and melanoma precursor, respectively. In this article, we describe the main clinical and dermoscopic characteristics and the management options for problematic lesions in children.

Introduction

Pediatric melanoma is extremely rare, especially before puberty. During the last congress of the American Academy of Dermatology, a famous pediatric dermatologist compared childhood melanoma to the legend of “Bigfoot,” a figure everybody is concerned about, but that only a few actually declare to have seen in their life. Of course she was not questioning the existence of childhood melanoma, but wanted to point the accent on the extreme rarity of this event and on the fact that, because of its rarity, no clear-cut clinical features and patterns of presentation are actually known. Most physicians will probably never be confronted with this malignancy, but even if they do encounter it, they might not readily recognize it. Recent findings in fact corroborated previous studies indicating that childhood melanoma does not present with conventional ABCDE criteria for melanoma. Most frequently it may mimic clinically nonmelanocytic lesions, such as angioma, pyogenic granuloma, viral wart, and molluscum. The same lesions are in the differential diagnosis of amelanotic/hypomelanotic Spitz nevi, which actually represent the main clinically and histopathologically challenging lesions to be differentiated from melanoma in this age group. In this scenario, it is not surprising that accuracy in melanoma detection in children still remains low. A recent study tested the accuracy in melanoma detection in children and adolescents over a 10-year period, using the NNE value (number needed to excise; obtained dividing the total number of excised lesions by the number of melanomas). The NNE value for this pediatric population (0–18 years) was 20 times higher than the rates usually found in adult patients, meaning that a very high number of benign nevi (ie, approximately 594) were excised to detect one melanoma. An effective strategy to reduce the number of unnecessary excisions would be to focus on problematic lesions. Epidemiologic data indicate that, apart from immune suppression and genetic conditions (such as xeroderma pigmentosum), the main risk factor for developing melanoma in a pediatric population is represented by the presence of a large congenital nevus. Thus, spitzoid lesions and congenital nevi have to be considered the true problematic lesions in children, representing melanoma simulator and melanoma precursor, respectively. In this article, we describe the main clinical and dermoscopic characteristics and the management options for problematic lesions in children.

Spitz/Reed nevi

Since the first description by Sophie Spitz in 1948, much work has been conducted in elucidating the clinico/pathologic variability of spitzoid lesions. Currently, common Spitz and Reed nevi are considered benign melanocytic proliferations that frequently occur in children and are histopathologically classified as benign without difficulty. At the other end of the spectrum of spitzoid lesions, we place “Spitzoid melanomas,” a morphologic type of melanoma with Spitzoid features, which are promptly identified as malignant on histopathologic examination. Between these 2 extremes are a series of Spitzoid lesions that present varying features of clinical and histopathologic atypia and unknown malignant potential that have been referred to with a variety of terms such as “Spitz nevus with atypia,” “atypical Spitz nevus,” “atypical Spitz tumors (AST)” and melanocytic tumors of uncertain malignant potential (MELTUMP). Some investigators have suggested the term of AST as the more widely accepted; however, no adequate histologic criteria exist to clearly classify these lesions as benign or malignant, and even experienced pathologists are unable to predict, in most cases, the outcome of this group of atypical Spitz lesions based on morphologic criteria. These uncertainties are the major reason why evidence-based management guidelines for Spitz tumors have not yet been established.

From a clinical point of view, a “classical” Spitz nevus presents as a pink or flesh-colored papule or nodule, rapidly growing, and appearing most frequently on the lower extremities or the head/neck region in childhood or adolescence. The histopathologic hallmark of Spitz nevi is the presence of large spindle and/or epithelioid cells, usually in the paucity or absence of melanin.

“Reed nevus” is the eponymic designation for a benign melanocytic lesion described by Reed and colleagues in 1975 as “pigmented spindle cell nevus.” It is mostly found in young adults on the lower extremities as a rapidly growing brownish-black macule or papule. On histopathology, it is described as made up of interconnecting junctional fascicles of heavily pigmented spindle cells. The autonomy of Reed nevus from Spitz nevus has been questioned because of the occurrence of cases of spindle and/or epithelioid cell nevi with heavy pigmentation, thus ascribing Reed nevus to the morphologic spectrum of Spitz nevus. At present, some investigators still maintain that Reed nevus is an entity that can be readily differentiated from pigmented spindle cell Spitz nevus. However, a clinicopathologic evaluation of a large case series showed that the histopathologic distinction between these 2 diagnostic categories is often a matter of great debate.

Dermoscopy

On dermoscopy, Spitz/Reed nevi can display 6 main dermoscopic patterns: vascular, globular, starburst, reticular, homogeneous, and atypical.

The vascular pattern is mainly composed of dotted vessels, which are monomorphic, regularly distributed throughout the lesion, and surrounded by regularly intersecting white lines, the so-called “reticular depigmentation.” A slight pigmentation can be present as a diffuse brownish to grayish hue with regular gray-brown, small to medium-sized globules.

In frankly pigmented lesions, globules are brown to black, large, and regularly distributed at the periphery, or surrounded by reticular depigmentation. In most cases of pigmented Spitz nevi, peripheral globules are fused with the central body of the lesion; these regular radial projections, the so-called streaks, give rise to a “starburst” appearance. In a minority of cases, a heavy pigmentation also determines the presence of a regular superficial black network. The homogeneous pattern is characterized by a diffuse dark brown to black-bluish color, which lacks the evidence of clear-cut streaks at the periphery.

Several of these features can be simultaneously present or irregularly distributed within a given lesion, thus giving an atypical pattern. Dermoscopic atypia also can be increased by the presence of a blue-whitish veil. As a general rule, Spitz nevus can be considered as potentially showing all the dermoscopic features of melanoma. The occurrence of an atypical dermoscopic pattern in Spitz nevus is well recognized and is an important mimic of melanoma. Moreover, melanoma may at times show very few or no dermoscopic features suggestive of malignancy, but may mimic Spitz nevus in exhibiting either the globular or the starburst pattern. The latter patterns have been described in such melanomas occurring in adulthood ( Fig. 1 ).

The many dermoscopic faces of Spitz/Reed nevi. ( A ) Hypomelanotic Spitz nevus showing a vascular pattern composed of dotted vessels regularly distributed throughout the lesion, and intersected by a white network. A few, regular, light brown globules are visible at the periphery. ( B ) Amelanotic Spitz nevus showing fairly regularly arranged dotted vessels on a “milky pink” background. ( C ) Atypical dermoscopic pattern of a Spitz nevus, showing linear irregular vessels, and an atypical pigment network on the upper right side of the lesion. ( D ) Typical starburst pattern in a small (“baby”) Reed nevus. ( E ) Dark brown and black globules irregularly distributed in a pigmented Spitz nevus. Blue-white blotches are also present centrally. ( F ) Heavily pigmented lesion (Reed nevus), with streaks at the periphery and a very evident superficial black network.

Management

Based on the inverse age distribution of Spitz nevi versus melanoma, with the number of Spitz nevi being highest in the first decade of life, some investigators have proposed conservative management for a classical or pigmented Spitz nevus appearing up to puberty. Relatively small (up to 1 cm) Spitz/Reed nevi, showing no atypical clinical and dermoscopic features, can be managed conservatively, with clinical and dermoscopic controls every 3 to 6 months. In the absence of sudden and marked changes in color, shape, or size, such a follow-up protocol can be continued until the appearance of a homogeneous pattern; thereafter, annual follow-up can be performed. During monitoring, the observed changes in dermoscopic patterns appear to represent different phases of the natural evolution of the nevus: the globular and starburst pattern are typical of the growth phase and the homogeneous or reticular pattern appears when the lesion becomes stable ( Figs. 2 and 3 ). During the growth phase, a marked increase in the diameter of the lesion, and substantial changes in the dermoscopic features, can be observed. These changes can sometimes produce a somewhat worrisome clinical and dermoscopic appearance, even after a very short follow-up period. In a recent study by Argenziano and colleagues, the investigators followed a series of 64 lesions in pediatric patients (mean age: 10.4 years) for a mean follow-up period of 25 months. In this study, 79.7% (n = 51) of the lesions showed an involution pattern and 20.3% (n = 13) showed a growing (n = 4) or stable pattern (n = 9). The great majority of growing lesions were pigmented or partially pigmented (92.3%), whereas 47.1% of lesions in involution were amelanotic ( P = .005). One pigmented growing lesion was excised by the investigators, and 6 were excised per patient request. All were histopathologically classified as Spitz nevi.

Different phases in the evolution of a pigmented Spitz nevus arising on the leg of a 2-year-old girl. ( A–C ) Clinical view at baseline, and after 4-month, and 12-month follow-up, respectively. ( D–F ) Corresponding dermoscopic images, showing a marked increase in the size of the nevus and increase in the number of peripheral globules and streaks around the lesion.

Involuting pigmented Spitz nevus arising in a 9-year-old boy. ( A, B ) Clinical view at baseline and after 8 months follow-up, respectively. ( C ) Heavily pigmented, reticular pattern under dermoscopy. ( D ) Partial involution of the network pattern, a blue-gray area of peppering is now visible in approximately half of the lesion surface.

AST

A clear-cut description of the clinico-dermoscopic features of ASTs has not yet been formally defined. However, according to retrospective histopathology studies, AST could be broadly outlined as a medium to large, nodular, sometimes ulcerated, hypopigmented or amelanotic spitzoid lesion. Thus, large (>1 cm), nodular, ulcerated, rapidly changing, or otherwise atypical Spitz nevi of childhood must be excised. Surgical excision is also recommended when Spitz nevi appear after puberty and during adulthood, regardless the presence of atypical clinical/dermoscopic features. Because of the absence of criteria that allow an accurate differentiation of nonpigmented Spitz nevi from pyogenic granuloma (lobular hemangioma), histopathologic examination is also recommended for those lesions showing features of pyogenic granuloma, independently of age ( Fig. 4 ). Of note, Requena and colleagues, in a recent clinico-pathologic study on 349 histologically proven Spitz nevi, found that only 18% of lesions were correctly diagnosed clinically. Clinical diagnoses included, among others, hemangioma, viral wart, xanthogranuloma, and molluscum contagiosum.

Spitz nevus and pyogenic granuloma. ( A, B ) Clinical photographs of a Spitz nevus ( A ) and a pyogenic granuloma ( B ) arising on the upper arm of an 11-year-old and 4-year-old boy, respectively. ( C, D ) Corresponding dermoscopy shows 2 amelanotic nodules surrounded by a collarette. The presence of a brownish background pigmentation and a few brown globules in the first lesion ( C ) could suggest the diagnosis of a melanocytic tumor; however, the exclusion of nonpigmented melanoma in both cases is extremely difficult and histopathologic examination is warranted.

When a diagnosis of AST is given by histopathologic examination, the clinician is faced with the challenging responsibility of choosing the best management option for their young patients ( Fig. 5 ). The management of AST is matter of great debate. In 2000, Kelley and Cockerell proposed that, in addition to wide excision, sentinel lymph node biopsy (SLN biopsy) should be considered for these patients. The presence of metastatic tumor deposits in the lymph node would support the malignant nature of the primary tumor. Against this theory is the evidence that none of the patients with primary ambiguous Spitz tumor and positive lymph nodes in the 7 published series died of metastatic melanoma to date. These findings may support the hypothesis that not all atypical Spitz tumors represent misdiagnosed conventional melanomas, but are perhaps a distinct category of “less aggressive” melanocytic tumors with loco-regional malignant behavior. Thus, SLN biopsy cannot be considered a diagnostic procedure, and moreover it has not been proven to represent a valuable prognostic tool in children. In addition to the known controversies around its survival benefit in adults, these considerations support the conclusion that, currently, the best treatment option for children diagnosed with AST is represented by complete excision of the primary lesion (ie, with sufficiently wide margin) and careful follow-up.

Atypical Spitz tumor. ( A ) A 2-cm plaque arising on the gluteal region of a 2-year-old girl. ( B ) Close-up view showing the presence of a central nodular area and variegated pigmentation. ( C ) Under dermoscopy, the lesion is spitzoid, showing reticular depigmentation, dot vessels, and peripheral streaks, but also displays centrally located milky red areas. Complete excision with narrow margins was performed and the histopathologic diagnosis of AST was confirmed by 2 experienced pathologists.

A recent survey among 175 pediatric dermatologists in the United States and around the world revealed that the previously mentioned management for Spitz nevi and atypical spitzoid lesions appears to be largely applied among physicians. Interestingly, in this survey, clinical follow-up was chosen by 49.3% of respondents for small, stable, and nonpigmented clinically suspected Spitz nevi, and by 29.7% of respondents for a pigmented lesion with a typical starburst pattern on dermoscopy. Furthermore, approximately 80% of the dermatologists surveyed reported using dermoscopy for their lesion assessments. These data show that conservative management for typical Spitz nevi is a clinical option chosen by many pediatric dermatologists, and highlight the widespread use of dermoscopy for the diagnosis of melanocytic lesions in the pediatric population. Importantly, the respondents to the survey had cared for only 2 patients who were thought to have died because of a lesion initially diagnosed as a Spitz nevus or atypical spitzoid neoplasm, an extremely small fraction of the approximately 20,000 Spitz nevi diagnosed by these dermatologists. Moreover, no deaths had resulted from the approximately 10,000 Spitz nevi and atypical spitzoid neoplasms seen by the 91 respondents with academic or hospital-based practices.