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Atypical negative ALK break-apart FISH harboring a crizotinib-responsive ALK rearrangement in non-small-cell lung cancer.

Anaplastic lymphoma kinase rearranged (ALK+) non–small-cell lung cancer demonstrates remarkable sensitivity to crizotinib.1 Although other methods exist, the dominant method for determining ALK positivity uses the Abbott (Abbott Molecular, Des Plaines, IL) ALK break-apart fluorescent in situ hybridization (FISH) assay.2 The assay has clearly defined positivity criteria but borderline or atypical negative cases occur. Here we describe a case with an atypical negative FISH result that was later confirmed as ALK+ by both immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) and responded well to crizotinib.