In “Lumps and Bumps Part 1” (“Pediatric Patient Care,” Skin & Aging, September 2006), four common cutaneous lesions in children were reviewed: pilomatricoma, pyogenic granuloma, juvenile xanthogranuloma and nevus sebaceous. In Lumps and Bumps Part 2, three additional common lesions will be reviewed: Spitz nevi, mastocytoses (mastocytoma and urticaria pigmentosa) and epidermal nevi.
The Spitz nevus is a melanocytic lesion with clinical and pathologic features that distinguish it from typical melanocytic nevi. Spitz nevi are often smooth, domed, pink-to-red papules. Pigmented lesions (brown to black) and more verrucous lesions also occur.1 What makes Spitz nevi challenging is that they can have histologic features that make them at times difficult to distinguish from melanoma.
In 1948, Spitz described a series of patients who had “juvenile melanomas”.1 She deemed them to be melanomas because these melanocytic lesions had many features similar to classic malignant melanoma. She distinguished these lesions from adult melanomas, however, by their having a less fatal course, distinct giant cells in about 50% of lesions, and fewer mitoses. These lesions became known as Spitz nevi.
Spitz nevi are usually easy to distinguish from typical melanocytic nevi in children. Many dermatologists accept that “typical” Spitz nevi, with their distinct clinical and histologic features, are benign lesions.2 However, some Spitz nevi demonstrate more atypia than a typical Spitz nevus, but not as much atypia as is seen in melanoma. These lesions have been called a variety of names including atypical Spitz nevi.
Atypical Spitz Nevi and Malignancy
This notion of atypical Spitz nevus generates much controversy. In reviewing the literature, Mones and Ackerman3 extensively make a cogent argument against the concept of the atypical Spitz nevus. They claim that if one upholds the basic principles of pathology and rules for malignancy, this intermediate or indeterminate category cannot exist; either it is a benign lesion or it is a malignant lesion.
Even Spitz’s original series contained a patient who died from metastases.1 Was this lesion a melanoma in the first place? Or can completely benign lesions become malignant? Mones and Ackerman3 would argue that metastases can only exist as part of malignancy and therefore the lesion was always a melanoma. Spatz et al4 describe a lesion considered low-risk for metastases that actually did metastasize. They took this to support the notion that an atypical Spitz nevus can metastasize rather than considering the original lesion to be malignant.
A survey of dermatologists found that 8% had seen melanoma in lesions previously described at Spitz nevi.2
While Mones’ and Ackerman’s2 arguments are compelling, there are clearly many authors who don’t want to label a lesion as a malignant melanoma when the histology deviates somewhat but not dramatically from the mild atypia often accepted in a typical Spitz nevus.
Attempts have been made to determine factors that might help indicate whether a given atypical lesion is benign or malignant. Immunohistochemistry has been used to try to differentiate Spitz from melanoma.
For example, Zhou and Fitzpatrick5 looked at c-kit (CD117) staining, but this showed no statistical difference between Spitz nevi and melanomas.
Hantschke, Bastian, and LeBoit6 describe a sign of “consumption of the epidermis — thinning of the epidermis with attenuation of the basal and suprabasal layers and loss of rete ridges in areas of direct contact with neoplastic melanocytes.” This sign was significantly more evident in clear cases of melanoma compared with Spitz nevi. However, in ambiguous cases — where it is most necessary to have distinguishing features — the consumption of epidermis was not significant in helping to distinguish lesions as benign or malignant.
Spatz et al4 tried to develop a grading system for risk stratification of Spitz nevi. They included in their grading system only the variables that had significance in distinguishing benign from malignant lesions. Then they graded and categorized the 30 cases on which this was based. Fifteen lesions were graded as low risk for metastases, six lesions were graded as intermediate risk, and nine lesions were graded at high risk. In their low-risk group, there was one patient who actually did have metastases and subsequently died.
While a grading system might be a helpful tool in analyzing difficult lesions, if even one patient who appeared to have a low-risk lesion dies, one needs to be careful of the utility of applying such a system.
Important Questions to Ask
Is there an intermediate lesion between Spitz and melanoma? Are all atypical Spitz nevi melanomas? Are there subtypes of melanoma that may have different behavior? These are not questions for which there are definite answers.
Were it not that clinicians need to make management decision about these lesions, it could remain in the arena of lively academic debate. Clinicians do need to make decisions about how to manage Spitz nevi as well as “atypical Spitz nevi.”
Management of Spitz Nevi
Gelbard et al2 surveyed dermatologists (general and pediatric) to determine how they approached Spitz nevi. A total of 381 dermatologists responded. Of these, 93% said they would biopsy a suspected Spitz, and 74% considered them benign lesions. Of those who would biopsy the lesion, 43% favored a full excision. For incompletely-excised lesions, 69% would re-excise them. Among those responding, a conservative approach was favored.
Sentinel node biopsy in Spitz nevi. Urso et al7 looked at lesions diagnosed as atypical Spitz nevi in which sentinel lymph node biopsies were done. Of these biopsies, 33% had positive nodes. No significant features could differentiate between the cutaneous lesions in those patients who were node-positive versus node-negative. Thus a lesion could not be considered definitively benign if the node was negative.
Roaten et al8 reviewed all cases of patients less than 21 years of age who had melanocytic lesions and had sentinel node biopsies. Three of 21 had Spitz nevi and of those, two had positive nodes. Complete lymph node dissection was negative. Survival for these cases was considered better than it would have been for a melanoma of similar depth and spread.
When dealing with malignant melanocytic lesions, most practitioners follow established management guidelines based on depth of the lesion and extent of spread of the disease.
In lesions that are clearly typical Spitz nevi, most dermatologists would excise or observe and offer reassurance.
For melanocytic lesions with unknown malignant potential, which includes the “atypical” Spitz nevus, a reasonable approach has been suggested by Kelley and Cockerell.9 If the lesion is less than 1 mm, excision with a 1-cm margin should suffice in conjunction with good clinical follow-up. For equivocal lesions greater than 1 mm in depth, a sentinel node biopsy could be performed. Cells present in the node that were similar to cells in the cutaneous lesion would confirm spread and could be worked up and managed as melanoma.
Not all authors accept that a Spitz nevus that spread to a node automatically confirms a malignant process. Therefore, it is important to be linked with surgeons and oncologists with whom to discuss equivocal lesions.
Four types of cutaneous mastocytosis exist:
1. urticaria pigmentosa (UP)
3. telangiectasia macularis eruptiva perstans (TMEP)
4. diffuse cutaneous mastocytosis.
Of these, only UP and mastocytomas are commonly seen. These are conditions where aggregates of mast cells produce localized lesions and mast cell mediators may produce symptoms. The involvement of other organs is rare in children.
Clinical Features. Urticaria pigmentosa typically presents as small brown papules, sometimes barely palpable. There can be a few scattered lesions or many. Mastocytomas are typically solitary and often larger than UP. Usually they are papules, plaques, or nodules. Bullae are relatively common among both UP and mastocytomas.10,11
Three relatively large retrospective chart reviews of cutaneous mastocytoses showed 65% to 80% of lesions were UP and 17% to 34% of cases were mastocytomas.10, 11, 12
All three retrospective reviews showed a very early onset of lesions. Ben-Amitai, Metzker, and Cohen showed that 93% presented in the first 2 years of life.10 Most (78%) patients had their first lesion before 13 months of age in another series.11 Kiszewski found 92% of patients had their first lesions in the first year of life.12 Interestingly, one study showed a relatively high percentage of congenital lesions — 19% of the UP lesions and 42.5% of the mastocytomas.10
While mastocytosis can present at any age (and many of these patients presented well after their first lesion), it is important to note that the history typically dates back to infancy. The lesions usually persist for several years and may not resolve until puberty.
Darier’s sign was positive in 89.5% of those in whom it was tested and documented.11 This was similar in Kiszewki’s series, which had positive Darier’s sign in 94%.12 This confirms this simple test as a useful diagnostic tool. It is not a perfect test, and the absence of a positive Darier’s sign does not preclude the diagnosis of mastocytosis.
Symptoms were reported in up to 50% of patients.11 Pruritus was most common, followed by flushing.11,12 Palpitations and hypotension were rare but reported.11
Management of Mastocytosis
Systemic work-up is not typically required as these patients rarely have systemic mastocytosis. Patients should have complete histories and physical exams with further work-up if abnormalities are detected. In one large retrospective review, all patients had routine physical exams, but no routine bloodwork.10
Management of cutaneous mastocytosis is aimed at symptom control and prevention of mast cell degranulation where possible. All patients who experience symptoms such as pruritus or flushing should be considered for treatment. The most common treatments are topical corticosteroids, oral antihistamines, and ketotifen.11 Some patients require daily antihistamines to prevent frequent symptoms. For solitary symptomatic mastocytomas, consider surgical excision.11
Epidermal Nevi (EN)
Clinical Features. Epidermal nevi are hamartomas that tend to follow Blaschko’s lines. They present at birth or in the first year.13 They often appear as coalescent grouped papules in a linear distribution and can become quite verrucous. They range in color from yellow-tan to dark brown. Uncommon variants include an acanthosis nigricans-like EN.14 Inflammatory linear verrucous epidermal nevus (ILVEN) is another variant of epidermal nevus that can be hard to distinguish from typical EN, lichen striatus and psoriasis.15
The pathogenesis of epidermal nevi is speculated to be related to cutaneous mosaicism. The specific phenotype may be associated with the type of genetic mutation or the timing of the mutation.16
Epidermal Nevus Syndrome (ENS) is a systemic disorder with epidermal nevus in association with central nervous system, ophthalmic, and skeletal abnormalities; there may sometimes be other organ involvement as well.16
A wide range of neurologic problems that may be associated include brain malformations, tumors and vascular malformation. Seizures, developmental delay and neurologic signs can ensue.
ENS may be a constellation of syndromes including: Proteus syndrome, congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome, phakomatosis pigmentokeratotica, sebaceous nevus syndrome, Becker’s nevus syndrome and nevus comidonicus syndrome.17
One series of EN patients describes 8% of their EN population as having an associated syndrome.17 They could fit most of their cases into the above categories, although none had Becker’s nevus syndrome. They also describe 13 patients who had epidermal nevi and one or more of CNS, eye problems, or musculoskeletal problems but without the cutaneous features of the other above syndromes. They propose that this be a distinct category.
Prognosis and Management of EN
Typically, EN are benign lesions that grow with a child. Early on, the lesion may appear to grow out of proportion to the child as its full extent is not always evident when it first appears. The lesions do not typically regress. While these lesions are often just cosmetic issues, there have been very rare cases of malignancy reported including squamous cell carcinoma.18
It is important with EN to perform a full history and exam to rule out the various associated syndromes. There is no routine work-up and any investigation would be based on findings from the history and exam.
Many treatment modalities have been tried, and size and location of the lesion may dictate the best option.
Small lesions may be amenable to surgical excision. Topical treatments with retinoids and keratolytics have been tried to improve appearance. A variety of lasers have been tried as well. Oral treatments such as isotretinoin (Accutane, Amnesteem, Claravis, Sotret) have been tried. There is also a report that etanercept (Enbrel) was able to improve pruritus, roughness and erythema in a case of ILVEN.19 As ILVEN is inflammatory, it is plausible that anti-inflammatory regimens might work.
Routine dermatological follow-up may be useful in selected cases. Typically, lesions could likely be monitored by primary-care
physicians and referred back to dermatology if any changes occur.