ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours

The aim of this study was to elucidate the pathological features of inflammatory myofibroblastic tumour (IMT) with gene rearrangement other than ALK.

We investigated anaplastic lymphoma kinase (ALK), ROS1, ETV6, NTRK3 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 ROS1 to be positive in 22 of 36 (61.1%) and two of 36 (5.6%) cases, respectively. In one case with ROS1 positivity, IHC staining showed cytoplasmic and dot-like ROS1 expression, and RT-PCR showed the presence of the TFG-ROS1 fusion transcript. Two cases of pulmonary IMT, in a 7-year-old patient and a 23-year-old patient, had ETV6 rearrangement, and the presence of the ETV6-NTRK3 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.

These results suggest that a subset of ALK-negative IMTs have rearrangement of ROS1, ETV6 or NTRK3 as a possible oncogenic mechanism, and that the detection of these alterations may be of diagnostic value and helpful for determining promising therapeutic strategies.