Pan-TRK Immunohistochemistry: An Example-Based Practical Approach to Efficiently Identify Patients With NTRK Fusion Cancer.

CONTEXT.­: Food and Drug Administration-approved TRK inhibitors with impressive overall response rates are now available for patients with multiple cancer types that harbor NTRK rearrangements, yet the identification of NTRK fusions remains a difficult challenge. These alterations are highly recurrent in extremely rare malignancies or can be detected in exceedingly small subsets of common tumor types. A 2-step approach has been proposed, involving a screening by immunohistochemistry (IHC) followed by a confirmatory method (fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction, or next-generation sequencing) in cases expressing the protein. However, there is no interpretation guide for any of the available IHC clones. OBJECTIVE.­: To provide a pragmatic update on the use of pan-TRK IHC. Selected examples of the different IHC staining patterns across multiple histologies are shown. DATA SOURCES.­: Primary literature review with PubMed, combined with personal diagnostic and research experience. CONCLUSIONS.­: In-depth knowledge of pan-TRK IHC will help pathologists implement a rational approach to the detection of NTRK fusions in human malignancies.