Background Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases. Methods This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.6‐15.8 years). RNA and cDNA were successfully obtained in 29 cases. The molecular analysis included sequential tests for 5′/3′‐end unbalanced gene expression, variant‐specific PCR, and next‐generation sequencing (NGS). Results 5′/3′‐end unbalanced ALK expression was revealed in 15/29 (52%) IMTs. Strikingly, all these tumors demonstrated high amount of ALK protein detected by immunohistochemistry. Variant‐specific PCR was capable of identifying the type of ALK rearrangement in 11/15 IMTs with 5′/3′‐end unbalanced ALK expression. The remaining four tumors were analyzed by NGS; two known and two novel (CLTC‐ins6del84‐ALK and EEF1G‐ALK) ALK rearrangements were detected. Five IMTs demonstrated 5′/3′‐end unbalanced ROS1 expression, and all these tumors carried TFG‐ROS1 fusion. Nine tumors, which were negative for 5′/3′‐end unbalanced ALK/ROS1 expression, were subjected to further analysis. Variant‐specific PCR revealed two additional tumors with gene rearrangements (TFG‐ROS1 and ETV6‐NTRK3). The remaining seven IMTs were tested by NGS; single instances of TFG‐ROS1 and novel SRF‐PDGFRb translocations were detected. Conclusions Twenty‐four of 29 IMTs (83%) were shown to have druggable rearrangements involving tyrosine kinases, 20 of these 24 gene fusions were detectable by simple and inexpensive PCR assay, which is based on the detection 5′/3′‐end unbalanced gene expression.

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Ewing’s sarcoma is a highly malignant small round cell tumor with a unique rearrangement of the EWSR1 (FUS) gene with partners genes of ETS family. Tumors with Ewing's sarcoma morphological features lacking without specific EWSR1 rear-rangement called undifferentiated small round cell sarcomas of bone and soft tissue. This group includes: sarcomas with СIC gene rearrangement, sarcomas with BCOR gene rearrangement and sarcomas with EWSR1 (FUS) gene rearrangement with non-ETS gene-partner. Clinical, morphological and molecular genetic characteristics of these groups of tumors will be described below