A fluorescence in situ hybridization (FISH) procedure to assist in differentiating benign from malignant melanocytic lesions

OBJECTIVE: Misdiagnosis of melanocytic lesions can result in unnecessary psychological distress to patients, under- or overtreatment, inaccurate prognosis and improper follow-up and family member surveillance. It is well recognized that, despite many attempts to 1) put forth a set of histologic criteria that can accurately and reproducibly be used to diagnose melanocytic lesions, and 2) identify reliable markers of malignancy as an adjunct to routine histopathology, misdiagnoses still occur in a significant number of cases. METHOD: A multi-color FISH probe mixture has been devised to assist pathologists in differential diagnosis of difficult melanocytic lesions. The mixture includes a centromeric probe for chromosome 6 and unique sequence probes for three other chromosomal regions that have most frequently shown amplifications or deletions in melanoma. We have carried out a preliminary evaluation of this new probe set in 25 cases of benign and malignant pigmented lesions. RESULTS: The tool reliably identified all nevi and ordinary melanomas, and only failed to identify a pigmented epithelioid melanocytoma and two malignant lesions that, by morphology and behavior, have distinct features from common invasive melanomas, i.e., a desmoplastic melanoma and a nevoid melanoma. Considering this, 100% specificity and 75% sensitivity was achieved. CONCLUSION: The FISH tool used in this study was able to separate accurately benign nevi from ordinary melanoma. Failure to identify uncommon melanocytic lesions adds to its advantage and calls for further studies to unveil the molecular profile of these rare entities.