Risk Assessment for Atypical Spitzoid Melanocytic Neoplasms Using FISH to Identify Chromosomal Copy Number Aberrations

*Department of Dermatology †Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago §§Abbott Molecular Laboratories, Des Plaines IL §Department of Pathology, University of Pennsylvania, Philadelphia, PA Departments of ∥Pathology ¶Dermatology, University of Michigan Medical Center, Ann Arbor, MI #Department of Pathology, Section of Dermatopathology **Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX ††Departments of Pathology and Dermatology, University of California, San Francisco ‡‡Department of Pathology and Laboratory Medicine, Dermatopathology, UCLA Medical Center, Los Angeles, CA ∥∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY ‡Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, The University of Sydney, NSW, Australia.
The American journal of surgical pathology (Impact Factor: 5.15). 02/2013; 37(5). DOI: 10.1097/PAS.0b013e3182753de6
Source: PubMed


Risk assessment for atypical Spitz tumors remains an enigma for physicians. Many prognosticators including sentinel lymph node biopsy fail to show the same prognostic significance in these tumors as seen in conventional melanoma. We conducted a case-controlled collaborative study involving multiple major melanoma treatment centers in the United States and Australia. Sixty-four atypical Spitz tumors with 5 years of uneventful follow-up and 11 atypical Spitz tumors resulting in advanced locoregional disease, distant metastasis, or death were evaluated by fluorescence in situ hybridization using 2 probe sets targeting 6 chromosomal loci. Predetermined criteria were utilized to detect the presence or absence of copy number aberrations for each locus. Logistic regression analysis, Fisher exact test, and multivariate analysis were performed to determine chromosomal copy number aberrations with statistically significant association with aggressive clinical behavior. Gains in 6p25 or 11q13 and homozygous deletions in 9p21 had statistically significant association with aggressive clinical behavior with P-values of 0.02, 0.02, and <0.0001, respectively. In multivariate analysis, homozygous 9p21 deletion was highly associated with clinically aggressive behavior (P<0.0001) and death due to disease (P=0.003). Fluorescence in situ hybridization detecting a limited number of chromosomal copy number aberrations can provide clinically useful and statistically significant risk assessment for atypical Spitz tumors. Cases with homozygous 9p21 deletions have the greatest risk. Cases with 6p25 or 11q13 gains also have higher risk for aggressive clinical behavior than FISH-negative atypical Spitz tumors or cases with 6q23 deletions.

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Available from: Douglas R Fullen, Mar 13, 2015
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