Classic and Atypical Spitz Nevi: Review of the Literature

Problems Differentiating Classic and Atypical Spitz Nevi From Melanoma

Melanoma is a major part of the differential diagnosis of Spitz nevi. The classic Spitz nevus typically has a benign nature, while the atypical Spitz nevus displays unpredictable behavior that appears to be dependent on the degree of atypia.^1,3,16 In contrast, melanoma is potentially fatal. Fortunately, Spitz nevi typically occur in children and the risk for having childhood melanoma is rare.^6,8,19 Though risk is minimal, rare cases of melanoma have been reported in children.^{8,11,14,15,19-21} Therefore, making a correct diagnosis and ruling out melanoma is important.

Unfortunately, even with clinical and histologic guidelines, sometimes it is difficult to distinguish classic and atypical Spitz nevi from melanoma. The major problem is histologic overlap with Spitz nevi and melanoma. Many researchers have emphasized that there is no single discriminating factor for Spitz nevi and melanoma because virtually every trait of Spitz nevi has been described in melanoma.^{2,10,13,20,22,23} Results of multiple studies show variability among researchers on the analysis of melanocytic nevi and melanoma lesions, and the final diagnosis was subjective.^5,22 In one retrospective study where clinical outcome was already known, 30 melanocytic lesions were evaluated independently by a panel of 10 dermatopathologists and categorized as either a typical Spitz nevus, atypical Spitz nevus, melanoma, tumor with unknown biologic potential, or other melanocytic lesion.⁵ The dermatopathologists were blinded to the clinical data. Evaluation of 17 Spitzoid lesions yielded no clear diagnostic consensus and a few lethal lesions were identified by most dermatopathologists as either typical or atypical Spitz nevi. The authors maintain that these results show that current objective criteria are deficient and inadequate to permit the discrimination of Spitz nevi with atypical features from melanoma.⁵

Given these histologic analysis limitations, many investigators are researching other tools and techniques that may help enhance diagnostic accuracy. Promising genetic analysis techniques include comparative genomic hybridization and fluorescent in situ hybridization.²⁴ In one study,²⁴ researchers compared Spitz nevi with primary cutaneous melanomas using comparative genomic hybridization and fluorescent in situ hybridization and discovered differences. In the study, Spitz nevi were found to have no chromosomal aberrations or gains in chromosome 11p or 7q21qter. In comparison, primary cutaneous melanomas had frequent chromosome deletions of chromosomes 9p, 10q, 6q, and 8p, and gains of chromosomes 7, 8, 6p, and 1q.^24,25 Immunohistochemistry is another potential tool for improving diagnostic accuracy. Examples of promising immunohistochemical markers include antibody MIB-1,^26-28 BCL-2,²⁹ and anti-S100A6.³⁰ Studies have shown that most melanomas are immunoreactive to MIB-1 and BCL-2, whereas Spitz nevi are not.^26-29 Recently, anti-S100A6 protein also was shown to be a potential immunohistochemical marker to differentiate a Spitz nevus from melanoma.³⁰ Anti-S100A6 is different from anti-S100 because it is more specific to a subclass of normal cell types and certain cancer cell lines. Investigators found strong, uniform, and diffuse S100A6 protein expression in the junctional and dermal components of all 42 Spitz nevi they studied versus weak and patchy S100A6 protein expression found mainly in the dermal component of 35 of 105 melanoma specimens they studied.³⁰ Although these techniques show exceptional potential, further research will be required to prove their reliability.

Management of Classic and Atypical Spitz Nevi

There is controversy regarding the treatment of a classic Spitz nevus. Some investigators recommend conservative treatment because a Spitz nevus is benign. They find that the Spitz nevus may be removed or left alone.³ Others agree but would add that complete excision with clinical follow-up is appropriate if there are atypical features found on the Spitz nevus.^16,23,31 Other investigators are more aggressive and recommend complete excision with clear margins of all Spitz nevi, unequivocal or not, because Spitz nevi have histologic overlap with melanoma, and recurrent lesions may present with pseudomelanomatous changes, which makes differentiation more difficult later.^4,32 They conclude that the benefits of complete excision outweigh the risks of partial treatment.⁴ Regardless of how a Spitz nevus case is managed, regular follow-up with a dermatologist is recommended to look for any changes or recurrences suggestive of malignancy.

Currently, there are no available evidence-based recommendations with predictive value for the specific management of atypical Spitz nevi because their clinical course is mostly unknown and unpredictable. Most articles that do address the management of atypical Spitz nevi state that they should be completely excised and followed periodically.^11,33 Murphy et al³⁴ suggest that an atypical Spitz nevus should be completely excised to avoid the rare possibility of a melanoma masquerading as an atypical Spitz nevus. Furthermore, if the physician is suspicious of malignancy, it is recommended that the lesion be managed like a melanoma and be removed in accordance with current melanoma margin guidelines or with comprehensive margin control via Mohs micrographic surgery.^34,35 Gurbuz et al¹⁷ stated that surgical margin excision, sentinel lymph node dissection, and clinical follow-up is recommended for atypical Spitz tumors. However, currently there are no prospective studies that have tested these various recommendations on atypical Spitz nevi management.