RARE DISEASE
Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor
Drug discovery
1
drug
With orphan designation
Overview
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential, characterized by myofibroblastic spindle cells, chronic inflammatory infiltrates, and frequent ALK gene rearrangements (50-80% of cases). It primarily affects young individuals, with local recurrence rates up to 30% and rare metastasis. Definitive diagnosis requires histopathology (spindle cells + inflammation) and molecular testing for ALK/ROS1/NTRK fusions.
Therapies
Localized disease: Complete surgical resection (curative in 70-80% of cases) [3][16][18].
Advanced/unresectable: ALK inhibitors (crizotinib, alectinib) for ALK-positive tumors (≥50% response), chemotherapy (anthracycline or methotrexate-based regimens), or radiotherapy [2][8][18].
Emerging options: Targeted therapy for ROS1/NTRK/RET fusions and immunotherapy trials [8][13].
Categories: rare neoplastic diseases
Research Papers
661 drug discovery papers about Inflammatory myofibroblastic tumor, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
661 drug discovery papers about Inflammatory myofibroblastic tumor, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-29 | Case Report: Recurrent uterine inflammatory myofibroblastic tumor harboring IGFBP5-ALK fusion with sustained response to iruplinalkib.
Inflammatory myofibroblastic tumor (IMT) is an extremely rare mesenchymal tumor with approximately 50% of cases harbor anaplastic lymphoma kinase (ALK) gene rearrangements. The tyrosine kinase inhibitor (TKI) treatment has been increasingly common for IMTs with ALK fusions, but evidence for the efficacy of TKIs in uterine IMT is lacking. In this report, we present a case of patient with recurrent uterine IMT harboring IGFBP5-ALK fusion. The patient was initially misdiagnosed as uterine myxoid leiomyoma and then leiomyosarcoma after recurring. Then the patient was recommended ALK-TKIs treatment after detecting ALK rearrangement, and achieved complete response (CR) from a second-generation ALK-TKI inhibitor, iruplinalkib, after resistance to the first-generation inhibitor crizotinib. This is the first case of iruplinalkib achieved therapeutic success in uterine IMT, suggesting that a sequential ALK-TKIs with iruplinalkib could be an optimal targeted therapeutic strategy for ALK-rearranged IMTs.
2026-05-28 | Molecular profiling and perioperative management of inflammatory myofibroblastic tumors at a single institution.
e23519 Background: Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm often driven by kinase fusions, most commonly involving anaplastic lymphoma kinase (ALK). Although tyrosine kinase inhibitors (TKIs) have demonstrated activity in unresectable IMT, the role of targeted therapy perioperatively is not well established. We evaluated the molecular profiles and clinical outcomes of IMTs at a single institution, describing the prevalence of actionable gene fusions and use of neoadjuvant targeted therapy. Methods: We performed a retrospective review of all patients with IMT at Columbia University Irving Medical Center from 2005 to 2025. Clinical and treatment data were analyzed. RNA-based fusion testing was performed on archival tumor specimens when available, and prior DNA/RNA sequencing results were reviewed when available. Results: Twenty-seven IMT patients were included. 59% were male and the average age at diagnosis was 41 years (range 1.5-81). Tumors arose in multiple sites, including the lung (22%), kidney (15%), head and neck (15%), and gastrointestinal tract (15%). 14 tumors underwent successful RNA-based sequencing, of which 12 (86%) harbored kinase fusions. ALK fusions were present in 9 (64%), ROS1 in 2 (14%), and a VCAN-IL23R fusion in one case. FN1-ALK was the most common fusion subtype (n=3), all occurring in bladder IMTs. Surgical resection was the primary treatment for 26/27 patients. Four patients received neoadjuvant therapy. Two patients with ALK-rearranged IMTs were treated with neoadjuvant ALK inhibition, resulting in one complete metabolic response (alectinib) and one partial response (crizotinib) prior to resection. The VCAN-IL23R case demonstrated recurrence and progression despite multimodal therapy. Two additional patients developed recurrence managed surgically. Conclusions: Kinase fusions were common (86% of sequenced tumors) and molecularly diverse in this IMT cohort, supporting routine use of RNA-based fusion profiling. Despite the high prevalence of actionable alterations, TKI use remained limited. The favorable responses to neoadjuvant ALK inhibition demonstrate the potential role for perioperative targeted therapy. The aggressive clinical phenotype seen in the VCAN-IL23R fusion case suggests that rare non-ALK fusions may represent biologically distinct IMT subsets with limited treatment options. Together, these findings support earlier incorporation of molecular testing with expanded investigation of rare gene fusions and highlight the need for prospective evaluation of perioperative TKI strategies. IMT molecular fusion profiles. Fusion Type N (%) Fusion partner(s) Tumor location Age range ALK 9 (64) FN1 (3), CLTC, MCC, TMP4, CLIP2, CSTF3, KIF5B Bladder (3), lung (3), head/neck (2), breast 2-77 ROS1 2 (14) FN1, TFG Lung, small intestine 13-18 IL23R 1 (7) VCAN Liver 12 No fusion detected 2 (14) N/A Epididymis, head/neck 70-78
2026-05-28 | Uterine Myxoid Inflammatory Myofibroblastic Sarcoma (MIMS) Harboring Pathogenic KRAS Mutations and Expressing ER, PR, and CD10.
Myxoid inflammatory myofibroblastic sarcoma (MIMS) is a recently described aggressive sarcoma with deceptively bland spindled cells with a myofibroblastic phenotype and myxoid stroma. These tumors are negative for ALK gene rearrangements, but have been shown to harbor gene fusions involving PDGFRA/B, JAK1, and PML and/or mutations involving KRAS. Only one uterine case has been previously reported. Here we report the second case of uterine MIMS. This tumor arose in a 40-yr-old woman patient and showed a conspicuously whorled architecture with myxoid stroma and so-called organoid aggregates. By immunohistochemistry, the tumor was positive for CD10, estrogen receptor (ER), and progesterone receptor (PR) with focal smooth muscle actin expression and no staining for ALK, desmin, h-caldesmon, HMB-45, or cathepsin-K. Next-generation sequencing analysis revealed the presence of 2 pathogenic mutations in KRAS, as well as pathogenic mutations in RAD51B and LATS1. No gene fusions in PDGFRA/B, JAK1, PML, ALK, ROS1, PLAG1, or any other gene were identified by whole transcriptomic RNA sequencing. Given its deceptively bland appearance and its propensity, at least in the uterus, to express both CD10 and ER with only focal SMA expression, MIMS can be mistaken for an endometrial stromal tumor, an ALK and ROS1-negative uterine inflammatory myofibroblastic tumor, or other cytologically bland fusion-driven uterine mesenchymal neoplasms.
2026-06-29 | Case Report: Recurrent uterine inflammatory myofibroblastic tumor harboring IGFBP5-ALK fusion with sustained response to iruplinalkib.
Inflammatory myofibroblastic tumor (IMT) is an extremely rare mesenchymal tumor with approximately 50% of cases harbor anaplastic lymphoma kinase (ALK) gene rearrangements. The tyrosine kinase inhibitor (TKI) treatment has been increasingly common for IMTs with ALK fusions, but evidence for the efficacy of TKIs in uterine IMT is lacking. In this report, we present a case of patient with recurrent uterine IMT harboring IGFBP5-ALK fusion. The patient was initially misdiagnosed as uterine myxoid leiomyoma and then leiomyosarcoma after recurring. Then the patient was recommended ALK-TKIs treatment after detecting ALK rearrangement, and achieved complete response (CR) from a second-generation ALK-TKI inhibitor, iruplinalkib, after resistance to the first-generation inhibitor crizotinib. This is the first case of iruplinalkib achieved therapeutic success in uterine IMT, suggesting that a sequential ALK-TKIs with iruplinalkib could be an optimal targeted therapeutic strategy for ALK-rearranged IMTs.
2026-05-28 | Molecular profiling and perioperative management of inflammatory myofibroblastic tumors at a single institution.
e23519 Background: Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm often driven by kinase fusions, most commonly involving anaplastic lymphoma kinase (ALK). Although tyrosine kinase inhibitors (TKIs) have demonstrated activity in unresectable IMT, the role of targeted therapy perioperatively is not well established. We evaluated the molecular profiles and clinical outcomes of IMTs at a single institution, describing the prevalence of actionable gene fusions and use of neoadjuvant targeted therapy. Methods: We performed a retrospective review of all patients with IMT at Columbia University Irving Medical Center from 2005 to 2025. Clinical and treatment data were analyzed. RNA-based fusion testing was performed on archival tumor specimens when available, and prior DNA/RNA sequencing results were reviewed when available. Results: Twenty-seven IMT patients were included. 59% were male and the average age at diagnosis was 41 years (range 1.5-81). Tumors arose in multiple sites, including the lung (22%), kidney (15%), head and neck (15%), and gastrointestinal tract (15%). 14 tumors underwent successful RNA-based sequencing, of which 12 (86%) harbored kinase fusions. ALK fusions were present in 9 (64%), ROS1 in 2 (14%), and a VCAN-IL23R fusion in one case. FN1-ALK was the most common fusion subtype (n=3), all occurring in bladder IMTs. Surgical resection was the primary treatment for 26/27 patients. Four patients received neoadjuvant therapy. Two patients with ALK-rearranged IMTs were treated with neoadjuvant ALK inhibition, resulting in one complete metabolic response (alectinib) and one partial response (crizotinib) prior to resection. The VCAN-IL23R case demonstrated recurrence and progression despite multimodal therapy. Two additional patients developed recurrence managed surgically. Conclusions: Kinase fusions were common (86% of sequenced tumors) and molecularly diverse in this IMT cohort, supporting routine use of RNA-based fusion profiling. Despite the high prevalence of actionable alterations, TKI use remained limited. The favorable responses to neoadjuvant ALK inhibition demonstrate the potential role for perioperative targeted therapy. The aggressive clinical phenotype seen in the VCAN-IL23R fusion case suggests that rare non-ALK fusions may represent biologically distinct IMT subsets with limited treatment options. Together, these findings support earlier incorporation of molecular testing with expanded investigation of rare gene fusions and highlight the need for prospective evaluation of perioperative TKI strategies. IMT molecular fusion profiles. Fusion Type N (%) Fusion partner(s) Tumor location Age range ALK 9 (64) FN1 (3), CLTC, MCC, TMP4, CLIP2, CSTF3, KIF5B Bladder (3), lung (3), head/neck (2), breast 2-77 ROS1 2 (14) FN1, TFG Lung, small intestine 13-18 IL23R 1 (7) VCAN Liver 12 No fusion detected 2 (14) N/A Epididymis, head/neck 70-78
2026-05-28 | Uterine Myxoid Inflammatory Myofibroblastic Sarcoma (MIMS) Harboring Pathogenic KRAS Mutations and Expressing ER, PR, and CD10.
Myxoid inflammatory myofibroblastic sarcoma (MIMS) is a recently described aggressive sarcoma with deceptively bland spindled cells with a myofibroblastic phenotype and myxoid stroma. These tumors are negative for ALK gene rearrangements, but have been shown to harbor gene fusions involving PDGFRA/B, JAK1, and PML and/or mutations involving KRAS. Only one uterine case has been previously reported. Here we report the second case of uterine MIMS. This tumor arose in a 40-yr-old woman patient and showed a conspicuously whorled architecture with myxoid stroma and so-called organoid aggregates. By immunohistochemistry, the tumor was positive for CD10, estrogen receptor (ER), and progesterone receptor (PR) with focal smooth muscle actin expression and no staining for ALK, desmin, h-caldesmon, HMB-45, or cathepsin-K. Next-generation sequencing analysis revealed the presence of 2 pathogenic mutations in KRAS, as well as pathogenic mutations in RAD51B and LATS1. No gene fusions in PDGFRA/B, JAK1, PML, ALK, ROS1, PLAG1, or any other gene were identified by whole transcriptomic RNA sequencing. Given its deceptively bland appearance and its propensity, at least in the uterus, to express both CD10 and ER with only focal SMA expression, MIMS can be mistaken for an endometrial stromal tumor, an ALK and ROS1-negative uterine inflammatory myofibroblastic tumor, or other cytologically bland fusion-driven uterine mesenchymal neoplasms.
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Drug Discovery Landscape
1 orphan drug designation for Inflammatory myofibroblastic tumor, including 1 approved therapy.
1 orphan drug designation for Inflammatory myofibroblastic tumor, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
crizotinib [Xalkori] | small molecules | FDA | 2021-12-20 | 2022-07-14 | Pfizer Inc. |
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