Differential Diagnosis of Melanomas Using Fluorescence In Situ Hybridization (FISH) – MelanoFISH.
Deloar Hossain, Junqi Qian, Joy Adupe, Krystyna Drewnowska, Stephen Varvel, Melanie M Wilk, David G Bostwick. Bostwick Laboratories, Glen Allen, VA
Background: Malignant melanoma is often difficult to distinguish from benign nevus. In this study, we investigated the utility of chromosomal anomalies in skin biopsy specimens to make this distinction by using multi-targeted fluorescence in situ hybridization (FISH).
Design: Skin biopsy specimens were retrospectively collected from patients with benign diagnoses (compound nevus, blue nevus, melanocytic nevus), dysplastic nevus (Clark's, compound, junctional, and residual), Spitz nevus, and melanoma. Each diagnosis was independently confirmed prior to study by two dermatopathologists. Unstained tissue sections were hybridized for 30 minutes using fluorescence-labeled oligo-DNA probes for chromosomes 6, 7, 11, and 20. Fluorescent signals for each chromosome were enumerated in 30 cells per case. A diagnostic criterion of gain in ten cells of any of these chromosomes or gains of any one chromosome in seven cells was considered positive.
Results: Evaluable FISH results were obtained in 465 cases. Numeric chromosomal anomalies which met the diagnostic criteria were found in 10% (20/205) of benign nevi, 5% (3/55) of dysplastic nevi, 39% (19/49) of Spitz nevi, and 72% (112/156) of melanomas. The mean number of cells with chromosomal changes was 3.4 for benign nevus, 2.8 for dysplastic nevus, 7.8 for Spitz nevus, and 13.8 for melanoma (melanoma vs. all other diagnoses, p<0.0001). The overall percent agreement between histologic diagnosis (melanoma vs. all others) and MelanoFISH results was 82%. The sensitivity = 72% (64-79%), specificity = 86% (82-90%). The area under the ROC curve was 0.79 (0.75-0.83), p < 0.0001.
Conclusions: Multi-targeted fluorescence in situ hybridization directed against chromosomes 6, 7, 11, and 20 can be useful for distinguishing melanoma from other melanocytic diagnoses. FISH appears less useful for distinguishing melanoma from Spitz nevus, an expected result given the known chromosomal anomalies in Spitz nevus similar to melanoma. Unlike other traditional non-oligo-based FISH probes, oligo-DNA probes required shorter hybridization time, allowing faster diagnostic evaluation.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 112, Tuesday Morning