Abstract
Morphologic heterogeneity among melanocytic proliferations is a common challenge in the diagnosis of melanoma. In particular, atypical melanocytic lesions in children, adolescents, and young adults may be difficult to classify because of significant morphologic overlap with melanoma. Recently a four-probe fluorescence in situ hybridization (FISH) protocol to detect chromosomal abnormalities in chromosomes 6 and 11 has shown promise for improving the classification of melanocytic lesions. We sought to determine the correlation between FISH results, morphology, and clinical outcomes in a series of challenging melanocytic proliferations in young patients. We retrospectively performed the standard four-probe FISH analysis on 21 melanocytic neoplasms from 21 patients younger than 25 years of age (range 5–25 years, mean 14.6 years) from Stanford University Medical Center who were prospectively followed for a median of 51 months (range 1–136 months). The study cohort included patients with 5 confirmed melanomas, 2 melanocytic tumors of uncertain malignant potential (MelTUMPs), 10 morphologically challenging atypical Spitz tumors (ASTs), and 4 typical Spitz nevi. FISH detected chromosomal aberrations in all five melanomas and in one MelTUMP, in which the patient developed subsequent lymph node and distant metastasis. All 10 ASTs, 4 Spitz nevi, and 1 of 2 MelTUMPs were negative for significant gains or losses in chromosomes 6 and 11q. Our findings demonstrated a strong correlation between positive FISH results and the histomorphologic impression of melanoma. This finding was also true for the MelTUMP with poor clinical outcome. Therefore FISH may serve as a helpful adjunct in the classification of controversial melanocytic tumors in young patients.
Highlights
A four-probe Fluorescence in situ hybridization (FISH) panel (6p25, centromere 6, 6q23, and 11q13), originally established by Gerami et al [12], has been used to analyze a range of melanocytic lesions, with more than 80% of known melanomas demonstrating positivity in the FISH panel [12], 34.7% of atypical Spitz tumors (ASTs) demonstrating negativity [13], and 15% of benign Spitz nevi demonstrating positivity for a gain in 11p [14], but current studies have not focused on a young patient population
Our study demonstrates the strong correlation between positive FISH results in melanocytic neoplasia in children and young adults ages 25 years and younger with morphologic features of melanoma, whereas negative FISH in patients with typical Spitz tumors and ASTs had a favorable long-term outcome
We focused our analysis on a group of controversial melanocytic neoplasms in which differentiation between malignant and benign was considered in 12 cases: 10 ASTs and 2 MelTUMPs
Summary
A four-probe FISH panel (6p25, centromere 6, 6q23, and 11q13), originally established by Gerami et al [12], has been used to analyze a range of melanocytic lesions, with more than 80% of known melanomas demonstrating positivity in the FISH panel [12], 34.7% of atypical Spitz tumors (ASTs) demonstrating negativity [13], and 15% of benign Spitz nevi demonstrating positivity for a gain in 11p [14], but current studies have not focused on a young patient population. There is increasing interest in the histopathologic diagnostic criteria and long-term outcomes of melanocytic lesions in younger age groups [3,4,5], and FISH provides a potential means of improved classification. We sought to determine the correlation between four-probe FISH results, morphology, and clinical outcomes in a series of challenging melanocytic proliferations in young patients with long-term prospective follow-up
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