Interpreting Discordant Monosomy 3 FISH and Chromosomal Microarray Analysis Results in Uveal Melanoma

Abstract Background: Uveal melanoma is the most common primary ocular tumor in adults and causes morbidity through lymphovascular metastasis. The presence of monosomy 3 in uveal melanomas is one of the most important prognostic indicators for metastasis. Two major molecular pathology testing modalities to assess monosomy 3 are fluorescent in situ hybridization (FISH) and chromosomal microarray analysis (CMA). Here, we report two cases of discordant monosomy 3 test results in uveal melanoma enucleation specimens using these molecular pathology tests.Case presentation: The first case is a uveal melanoma from a 51-year-old male that showed no evidence of monosomy 3 by CMA, but was subsequently detected by FISH. The second case is a uveal melanoma from a 49-year-old male that showed monosomy 3 at the limit of detection by CMA that was not detected by subsequent FISH.Conclusions: These two cases underscore the differences of each testing modality for monosomy 3. The high percentage of cells with one chromosome 3 signal requisite for a positive monosomy 3 FISH result may not be sensitive enough to detect a low level of monosomy 3 that CMA can detect. Conversely, a small uveal melanoma with monosomy 3 may be missed by CMA owing to background DNA from cytologically normal retina and other ocular tissues. Our cases suggest that both testing methods should be pursued for uveal melanoma, with a single positive result for either test interpreted as presence of monosomy 3.