Background: The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions. Methods: A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens. Results: Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9% of nevus without atypia, while genetic abnormalities were identified in 6.3%, 6.7%, and 10.3% of nevus identified with mild, moderate and severe atypia, respectively. Conclusions: Based on this study, inheritable genetic damage/instability identified by FISH testing is a hallmark of a progressive malignant process, and a valuable diagnostic tool for the identification of high risk lesions.
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