ALK,ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours

Aims The aim of this study was to elucidate the pathological features of inflammatory myofibroblastic tumour ( IMT ) with gene rearrangement other than ALK . Methods and results We investigated anaplastic lymphoma kinase ( ALK ), ROS 1, ETV 6, NTRK 3 and RET in 36 cases of IMT by using immunohistochemical ( IHC ) staining, fluorescence in‐situ hybridization, and reverse transcription polymerase chain reaction ( RT ‐ PCR ). IHC staining showed ALK and ROS 1 to be positive in 22 of 36 (61.1%) and two of 36 (5.6%) cases, respectively. In one case with ROS 1 positivity, IHC staining showed cytoplasmic and dot‐like ROS 1 expression, and RT ‐ PCR showed the presence of the TFG – ROS 1 fusion transcript. Two cases of pulmonary IMT , in a 7‐year‐old patient and a 23‐year‐old patient, had ETV 6 rearrangement, and the presence of the ETV 6– NTRK 3 fusion transcript was confirmed in one case. These tumours were composed of hypocellular myxoid areas and highly cellular areas with rich plasmacytic infiltration; the histological features were different from those of infantile fibrosarcoma. RET rearrangement was not detected. Conclusions These results suggest that a subset of ALK ‐negative IMT s have rearrangement of ROS 1 , ETV 6 or NTRK 3 as a possible oncogenic mechanism, and that the detection of these alterations may be of diagnostic value and helpful for determining promising therapeutic strategies.