Diagnostic utility of pan-Trk immunohistochemistry for inflammatory myofibroblastic tumours

Aims Inflammatory myofibroblastic tumour (IMT) is a spindle cell neoplasm of intermediate malignancy, and the diagnosis is often challenging due to the morphological overlap with other spindle cell neoplasms and reactive lesions. More than half of IMTs have the ALK gene rearrangement, and a minor subset have ROS1, NTRK3 or RET gene rearrangements. We sought to determine the potential diagnostic utility of pan-Trk immunohistochemistry for IMTs. Methods and results We retrospectively examined 40 cases of IMT using immunohistochemistry with a rabbit monoclonal pan-Trk antibody. Gene rearrangement was confirmed by fluorescence in-situ hybridisation and/or reverse transcription-polymerase chain reaction. The IMTs were classified as the ALK (n = 29), ROS1 (n = 2), NTRK3 (n = 2), RET (n = 0) and 'quadruple-negative' (n = 7) genotypes by molecular analyses. Both of the ETV6-NTRK3 fusion-positive cases showed nuclear and cytoplasmic staining for pan-Trk in the majority of tumour cells. None of the ALK, ROS1 or quadruple-negative-type IMTs showed nuclear staining for pan-Trk, but approximately one-third of these IMTs showed focal and weak cytoplasmic staining. One exceptional case of a RANBP2-ALK-positive epithelioid inflammatory myofibroblastic sarcoma (an aggressive variant of IMT) showed moderate cytoplasmic staining for pan-Trk. Conclusions These results suggest that pan-Trk immunoreactivity with a nuclear and cytoplasmic staining pattern may be useful to identify ETV6-NTRK3-positive IMTs and may be helpful in selecting patients for Trk-targeted therapy.