Therapeutic options in inoperable ROS1-rearranged inflammatory myofibroblastic tumor of the tongue in a child: a case report and literature review

Abstract

Inflammatory myofibroblastic tumor (IMT) is a rare borderline malignancy, usually treated with surgery only. Exceedingly rare cases of inoperable, recurrent, or metastatic IMTs pose a therapeutic challenge. We report successful treatment of a 7-year-old girl with an inoperable anaplastic lymphoma kinase (ALK)-negative IMT of the tongue. The patient underwent various antiinflammatory (steroids, nonsteroidal anti-inflammatory drugs, clarithromycin) and antiproliferative (chemotherapy) therapies to enable tumor regression and complete resection. Ultimately, next-generation sequencing of the tumor revealed a TFG-ROS-1 translocation, allowing for an off-label targeted therapy with crizotinib. Crizotinib treatment caused slight tumor regression but evident change of its structure, allowing for complete nonmutilating resection. Two histopathology examinations revealed complete disappearance of neoplastic cells following therapy. The patient remains disease-free 22 months after the delayed surgery. In children with inoperable ALK-negative IMTs, molecular testing must be performed to identify other targetable oncogenic fusions, including TFG-ROS1.

Reclassification of a spindle cell sarcoma after identification of a TFG‐ROS1 fusion: A case demonstrating the clinical benefit of next‐generation sequencing in sarcoma

“…Of the 17 other reports of ROS1 fusion containing IMTs we identified, 10 had a TFG-ROS1 fusion (Ambati et al, 2018;Antonescu et al, 2015;Carcamo et al, 2021;Ingley et al, 2021;Lovly et al, 2014;Mai et al, 2019;Sommer et al, 2024;Styczewska et al, 2021;Yorke et al, 2023), two had a YWHAE1-ROS1 fusion (Lovly et al, 2014;Comandini et al, 2021), and the fusion partner was not reported in five (Antonescu et al, 2015;Vassal et al, 2016). Of 15 cases where demographic data were available, the patients ranged in age from 4 to 61 years.…”

Comment on: Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

“…outcomes of ROS1-fusion positive IMT. 1,6,[8][9][10][11][12][13][14][15] In Pire et al, none of the ROS1-fusion positive IMTs presented with metastases, whereas six patients in recent case reports had metastases. [8][9][10][11]13 These six reported metastatic cases represent 40% of the 15 published cases of ROS1-fusion IMTs with sufficient clinical information to determine whether there were metastases at diagnosis (Table 1).…”

“…Successful treatment of metastatic, recurrent, and non-resectable IMT driven by ALK, ROS, and NTRK fusions with tyrosine kinase inhibitors has been described. 1,4,6,[8][9][10][11][12][13][14][15][16][17][18]…”

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

“…Due to the heterogeneous genetics of IMT and various gene fusions, it is necessary to introduce other targeted therapies. The presence of ROS1 fusion genes has been proven; Reports on the therapy of these patients are poorer, but case reports showed the efficacy of standard ALK inhibitors in this case [ 210 , 226 , 227 ]. As mentioned above in the Genetics section, IMT may harbour neurotrophic tropomyosin receptor kinase (NTRK) gene rearrangements.…”