Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis

Abstract

A subset of Spitz nevi poses substantial diagnostic difficulty, even among experts, due to its resemblance to malignant melanoma. These lesions are termed atypical Spitz nevi/tumors and there is currently a lack of objective criteria for predicting their biologic behavior. We compared the expression of Ki-67, p21, and fatty acid synthase by immunohistochemistry in 10 atypical Spitz nevi, 28 typical Spitz nevi, 19 compound melanocytic nevi and 18 invasive malignant melanomas. There was a progressive increase in fatty acid synthase cytoplasmic expression with statistically significant differences observed between Spitz nevi and atypical Spitz nevi (P ¼ 0.003) and between atypical Spitz nevi and malignant melanoma (Po0.050). Ki-67 nuclear staining was lower in both typical and atypical forms of Spitz lesions than in malignant melanoma (Po0.001). The degree of P21 nuclear expression in atypical Spitz nevi was not significantly different than in Spitz nevi, but was significantly greater than expression in conventional nevi and approached significance after multiple comparisons corrections for malignant melanoma. Thus, a high level of P21 expression makes a tumor more likely to be a typical or atypical Spitz nevus than a malignant melanoma, especially when coupled with a low Ki-67 index and weak expression of fatty acid synthase. These immunohistochemical observations support the concept that atypical Spitz nevi are distinct lesions of borderline biologic behavior residing between Spitz nevi and malignant melanoma. The study also compared a large array of histologic features of 16 cases of typical Spitz nevi in children with 12 typical Spitz nevi in adults. The adult lesions were significantly more likely to be intradermal and to display dermal fibroplasia, but were histologically similar to their pediatric counterparts in all other respects.

Fatty acid synthase expression in cutaneous melanocytic neoplasms

“…Some of these cases have been previously published. 16 Of the primary malignant melanomas, the Breslow depth was less than 0.75 mm in 25 cases, between 0.75 and 1.50 mm in seven cases, and greater than 1.50 mm in 16 cases. The following clinical information was obtained from the patients' medical records: age, sex, location of lesion, size of the lesion, duration, therapy, and follow-up.…”

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

“…19 For CD117, nestin, clusterin, SOX10 and CD271 (p75NTR), cut-off values for scoring were the following: negative or 0 ¼ o10%, 1 ¼ 11-25%, 2 ¼ 26-50% and 3 ¼ 450%. For purposes of statistical analyses, cases with 11% or more were considered positive.…”

The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study

“…[2][3][4][5] Furthermore, most lesions do not show many of the conventional criteria that are used routinely for the histopathologic diagnosis of the tumor, thus emphasizing the lack of objective criteria for predicting the biologic behavior of such lesions. 3,6,7 The classification of some cases as metastasizing Spitz nevi 1 illustrates the difficulty of accurately distinguishing some Spitz nevi from melanoma based solely on histological criteria.…”