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
672 drug discovery papers about Inflammatory myofibroblastic tumor, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
672 drug discovery papers about Inflammatory myofibroblastic tumor, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2025-06-25 | Uterine Inflammatory Myofibroblastic Tumor Mimicking Myoma Treated With Gonadotropin-Releasing Hormone Therapy: A Case Report.
Inflammatory myofibroblastic tumors (IMTs) of the uterus are a rare entity that can be challenging to distinguish from leiomyomas, both radiologically and pathologically. No previous reports have documented the response of uterine IMT to gonadotropin-releasing hormone (GnRH) therapy. A 47-year-old Japanese woman presented to our hospital with excessive menstruation and uterine prolapse. Magnetic resonance imaging (MRI) revealed four well-demarcated uterine masses, with the largest measuring 81 mm. Myomas were suspected. Oral GnRH therapy was initiated to relieve the symptoms and reduce the preoperative volume. After four months, follow-up MRI showed a reduction in the largest mass to 62 mm and increased hyperintense areas on T2-weighted images. At six months, the patient underwent laparoscopic hysterectomy and colporrhaphy. Histopathological examination revealed that the largest tumor was an IMT with abundant myxoid matrix, positive for anaplastic lymphoma kinase (ALK), and ALK gene rearrangement. The remaining three masses were diagnosed as usual-type leiomyomas. This is the first reported case of uterine IMT treated with GnRH therapy, which resulted in notable tumor shrinkage. This case highlights both the potential therapeutic approach for uterine IMT and the diagnostic difficulty in distinguishing it from leiomyomas preoperatively.
2024-07-17 | Recurrent Inflammatory Myofibroblastic Tumor of the Larynx: Presentation and Management
Laser-assisted wide excision of the lesion was performed and since the lesion was confirmed during surgery to be attached to the left vocal process and arytenoid, an area more prone to frictional injury due to phonation, adjuvant treatment of botulinum toxin injection into the left thyroarytenoid muscle was performed.A total dose of 7.5 mu of botulinum toxin was injected during the surgery into the left thyroarytenoid muscle.Histopathological examination revealed a spindle cell tumor (Fig. 2) and immunohistochemistr y was positive for pan-cytokeratin (pan-CK), epithelial membrane antigen (EMA), smooth muscle actin (SMA), and in Ki-67 it showed 1-
2020-06-19 | Inflammatory Myofibroblastic Tumor of the Uterus
Inflammatory myofibroblastic tumors (IMT) of the uterus may be underrecognized as their morphology and immunophenotype may overlap with myxoid variants of uterine smooth muscle tumors and endometrial stromal tumors. Although ALK is a helpful biomarker, not all uterine IMTs are ALK -rearranged, and a small subset of myxoid leiomyosarcomas is ALK-positive. Herein, we evaluated a series of 23 IMTs for the novel endometrial stromal markers interferon-inducible transmembrane protein-1 (IFITM1) and BCOR, the novel myoid marker transgelin, and possible predictive markers p16 and p53 by immunohistochemistry to determine their expression profile and potential prognostic value. Patients’ ages ranged from 8 to 59 (mean 39) years and tumors from 2 to 20 (mean 8.2) cm. Follow-up was available for 12/23 (52%) patients; 9/12 (75%) without evidence of disease, 2/12 (17%) alive with disease, and 1/12 (8%) dead from disease. Four IMTs were classified as malignant due to extrauterine disease at diagnosis and/or recurrence. IFITM1 was positive (combined score>2) in 19/23 (83%), BCOR in 8/20 (40%), and transgelin in 22/23 (96%) of tumors. IFITM1 and BCOR were more often expressed in the myxoid component, and transgelin in the compact areas. p16 expression was absent in 5/23 (22%) of IMTs, while p53 was wildtype in all tumors. p16-negative IMTs included all 4 classified as malignant and one where the patient was lost to follow-up. Molecular data were available in 2 malignant IMTs, both of which harbored CDKN2A deletions. We conclude that caution is advised when using IFITM1, BCOR, and transgelin as markers for endometrial and smooth muscle tumors, as these are commonly expressed in IMTs. However, we did identify an association among lack of p16 staining, CKDN2A deletions, and aggressive behavior that merits corroboration by other studies. As a result of this finding, we recommend the use of p16 in the diagnostic work-up of uterine IMTs due to its potential prognostic significance.
2019-02-26 | Targeting ALK in Cancer: Therapeutic Potential of Proapoptotic Peptides
ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more. This makes ALK an attractive target for cancer therapy. Since ALK–driven tumors are dependent for their proliferation on the constitutively activated ALK kinase, a number of tyrosine kinase inhibitors have been developed to block tumor growth. While some inhibitors are under investigation in clinical trials, others are now approved for treatment, notably in ALK-positive lung cancer. Their efficacy is remarkable, however limited in time, as the tumors escape and become resistant to the treatment through different mechanisms. Hence, there is a pressing need to target ALK-dependent tumors by other therapeutic strategies, and possibly use them in combination with kinase inhibitors. In this review we will focus on the therapeutic potential of proapoptotic ALK-derived peptides based on the dependence receptor properties of ALK. We will also try to make a non-exhaustive list of several alternative treatments targeting ALK-dependent and independent signaling pathways.
2017-02-08 | Cytokine Interferon-γ suppresses the function of capsule myofibroblasts and induces cell apoptosis
ABSTRACT Myofibroblasts (MFs), a contractile subset of fibroblasts, play a pivotal role in physiological wound healing and in the development of many fibroconnective disorders. The complex cytokine network regulating the function of MFs in joint stiffness is still poorly understood. In this in vitro study, we investigated the effect of the cytokine Interferon‐gamma (IFN‐γ) on MFs isolated from human joint capsules. MFs were cultivated either in the presence of increasing concentrations of IFN‐γ alone or in combination with IFN‐γ neutralizing antibodies. Cell viability, cytotoxicity, apoptosis, and mRNA gene expression of the MF markers alpha‐smooth muscle actin (α‐SMA) and collagen type I were analyzed in MF cultures. Contraction potential was analyzed in an established collagen gel contraction assay simulating the extracellular matrix. Using immunofluorescence staining, we could verify that MFs express IFN‐γ‐receptor (R)‐1 on their membrane. IFN‐γ decreased MF viability and significantly elevated the apoptosis rate in a dose‐dependent manner. IFN‐γ down‐regulated α‐SMA and collagen type I mRNA expression which was associated with a diminished MF mediated contraction of the gel matrices. These effects were suppressed by simultaneous treatment of cells with a neutralizing IFN‐γ antibody. Our experiments confirm the hypothesis that the cytokine IFN‐γ is a crucial component of the regulatory network of capsule MFs. IFN‐γ notably influences the ability of MFs to contract collagen matrices by suppressing α‐SMA gene expression. IFN‐γ is toxic for MFs in high concentrations and may negatively regulate the number of pro‐fibrotic MFs during the healing process via induction of cell apoptosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2524–2533, 2017.
cell therapies
2023-10-30 | Heart Transplantation as a Treatment Option for Recurrent Myxofibrosarcoma: A Clinical Case.
Myxofibrosarcoma is one of the most rare tumors of the heart. Surgical resection is the principal method of treatment; however, in some cases, radical removal of the tumor is not possible. Here, we present a case of heart transplant in a patient who experienced recurrent myxofibrosarcoma of the left atrium and examine the morphological features of this tumor. A 40-year-old female patient presented for treatment for heart failure of a high functional class. An examination revealed a tumor in the left atrial cavity, which was subsequently surgically removed. Morphological examination revealed an inflammatory myofibroblastic tumor. After 2 years, the patient's tumor recurred. The tumor was removed, and a morphological study again diagnosed myxofibrosarcoma of the heart. A year later, recurrence was again diagnosed. Instrumental examination determined that the tumor had incurred into the mitral valve and possibly spread to the myocardium. Tumor resection was not possible, and the need to perform a heart transplant was determined. The given case contributes to the practical conclusion that heart transplant contributes to an increase in the life expectancy for patients with inoperable cases of cardiac sarcoma.
2023-09-28 | Flexible bronchoscope for the treatment of intratracheal inflammatory myofibroblastic tumor in children: a case report and literature review
Abstract Background Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor. In children, it most often occurs in the lung tissue and the trachea is rarely involved. Inflammatory pseudotumor is multifactorial in etiology and generally benign, but it is often mistaken for malignancy given its aggressive appearance. Although IMT is a benign tumor, it has the possibility of malignancy, recurrence and distant metastasis, and surgical resection is the first choice for its treatment. Case Presentation: we report a case of a 5-year-old boy with clinical symptoms of cough, wheezing, shortness of breath, and hemoptysis. Flexible bronchoscopy showed that the mass was obstructing the airway. The patient was diagnosed as anaplastic lymphoma kinase (ALK) positive IMT by pathological and immunohistochemical examination. After multiple times of flexible bronchoscopic cryotherapy under general anesthesia, the mass disappeared completely, and no recurrence was found in 6 years of follow-up. Conclusion IMT in the airway is rare in children and should be distinguished from asthma and other airway obstructive diseases when clinically encountered. The preferred treatment method is surgery. Children with simple IMT who are not suitable for surgery can choose bronchoscopic interventional therapy, which not only has high safety, but also reduces the risk and complications of surgery, and also reduces the financial burden of patients' families.
2023-04-20 | Liver transplantation for hilar inflammatory myofibroblastic tumor: Case report and review of the literature.
Inflammatory myofibroblastic tumors (IMTs) of the liver are rare neoplasms. These tumors are difficult to distinguish from other neoplasms by radiological examination, have uncertain evolution, and there is no consensus on the treatment of these lesions. Hilar tumors can involve the portal vein, hepatic artery, bile duct, and spread to the branches of the portal triad, causing obstructive symptoms, occlusive phlebitis, and portal hypertension. Thus, liver transplantation (LT) is an excellent alternative for locally advanced hilar tumors, since it ensures complete tumor resection with free margins. We present a literature review and a case report showing a 3-year-old boy with liver IMT invading the hepatic hilum and inferior vena cava, who underwent a successful living donor liver transplantation that required portal vein and vena cava replacement. The incidence of hilar IMTs is low and there is no well-established standard treatment. Liver transplantation for a hilar tumor with vascular invasion was acceptable in this case because the radically of the surgery was the key for the cure, and because the tumor was benign in nature.
2016-08-19 | The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation
State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.
2008-07-01 | Successful Orthotopic Heart Transplant in an Infant With an Inflammatory Myofibroblastic Tumor of the Left Ventricle
A female infant was diagnosed with an inflammatory myofibroblastic tumor involving the left ventricle, which compromised cardiac function. The tumor was endocardial in location and resection was not possible. In this study we report the first successful cardiac transplant and long-term follow-up for this indication. A female infant was diagnosed with an inflammatory myofibroblastic tumor involving the left ventricle, which compromised cardiac function. The tumor was endocardial in location and resection was not possible. In this study we report the first successful cardiac transplant and long-term follow-up for this indication.
small molecules
2026-08-13 | Gastric inflammatory myofibroblastic tumor in adults: a case report and literature review.
Gastric inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, with adult cases being particularly uncommon. We report a 64-year-old man with an incidentally detected gastric mass that was preoperatively suspected to be a gastrointestinal stromal tumor (GIST). The relevant literature on adult gastric IMT was also reviewed. Complete surgical resection with negative margins (R0 resection) remains the mainstay of treatment, whereas patients with confirmed ALK rearrangements may benefit from ALK inhibitor therapy. Histopathological confirmation and long-term surveillance are essential because of the potential for recurrence and occasional aggressive behavior.
2026-08-11 | Case Report: Dose-escalated volumetric modulated arc therapy achieving bowel and renal protection for large retroperitoneal inflammatory myofibroblastic tumor invading ureter and inferior vena cava
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm for which definitive radiotherapy in the retroperitoneum remains largely undefined, particularly when dose escalation must be balanced against the preservation of adjacent critical organs. A 59-year-old woman presented with a 10-day history of fever and abdominopelvic pain. Physical examination revealed deep tenderness in the right lower quadrant, and laboratory testing demonstrated leukocytosis. Imaging identified a 9.2 cm retroperitoneal mass invading the right ureter and inferior vena cava. Biopsy confirmed IMT, and capture-based next-generation sequencing revealed no class I actionable alterations. Given the unfavorable surgical anatomy and limited response to corticosteroids, curative-intent resection was precluded. The patient was treated with definitive dose-escalated volumetric modulated arc therapy (VMAT) employing a simultaneous integrated boost strategy (66 Gy/33 fractions to the boost volume and 50 Gy to the conventional planning target volume), with spatial sparing of adjacent organs at risk. Complete radiographic response was achieved at one month, without grade ≥2 treatment-related adverse events. At 19-month follow-up, the patient remained disease-free with stable renal function. This case demonstrates that dose-escalated VMAT with spatial organ avoidance can achieve durable complete remission in unresectable retroperitoneal IMT while preserving organ function, supporting its consideration as a curative-intent strategy in this challenging clinical setting.
2026-08-05 | Inflammatory myofibroblastic tumour: unravelling the interplay of inflammation, kinase signalling, and therapeutic resistance.
Inflammatory myofibroblastic tumour (IMT) is a mesenchymal tumour characterised by myofibroblastic cells and the presence of inflammatory cells, such as macrophages, neutrophils, and lymphocytes. IMT can originate from diverse anatomical locations within the body. The macrophage-rich immune microenvironment contributes to cytokine release and inflammation, but IMT is primarily driven by oncogenic alterations. Oncogenic fusions, most commonly involving anaplastic lymphoma kinase (ALK), and other genes, such as ROS1 and NTRK3, are seen in most IMTs. Upregulation of these genes activates downstream signalling pathways such as RAS/MAPK and PI3K/AKT, leading to uncontrolled cell proliferation. Constitutive tyrosine kinase activation disrupts cell-cycle control by suppressing p21/p27, inactivating Rb, and impairing p53-dependent checkpoints, thereby limiting apoptosis. Combining surgery with targeted kinase inhibitors remains the primary therapeutic approach, especially for ALK-positive IMT. On the contrary, ALK-negative IMT harbours distinct oncogenic fusions and is driven by diverse signalling pathways. Thus, it requires therapeutic methods targeting the specific molecular alterations. Resistance to ALK inhibitors can emerge during treatment. This resistance arises through bypass signalling, epigenetic changes, and secondary mutations. This review aims to analyse the interplay between inflammation and genetic fusions in the origin and progression of IMT. The review provides an overview of the therapeutic approaches currently in use, mechanisms of treatment resistance, and potential techniques to improve diagnosis and develop personalised therapeutic strategies.
2026-07-29 | Precision oncology for ALK positive inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with a broad clinical spectrum, ranging from indolent localized lesions to aggressive metastatic disease. Approximately half of IMTs harbor oncogenic anaplastic lymphoma kinase (ALK) gene fusions, which drive constitutive kinase activation and render the tumors sensitive to ALK tyrosine kinase inhibitors (ALK-TKIs). Although ALK-targeted therapy has significantly improved outcomes in IMT patients, durable responses are frequently limited by intrinsic and acquired resistance. In this review, we summarize the molecular taxonomy and functional stratification of ALK fusion variants in IMT, highlighting their diagnostic and therapeutic implications. We outline a tiered diagnostic workflow integrating immunohistochemistry, fluorescence in situ hybridization, and RNA-based next-generation sequencing to optimize fusion detection and guide precision treatment selection. We also discuss the major mechanisms of ALK-TKIs resistance—including on-target kinase domain mutations, off-target bypass pathway activation, and lineage plasticity—and propose corresponding clinical countermeasures. Finally, we review emerging therapeutic strategies such as third-generation ALK-TKIs, TRK-sparing brain-penetrant compounds, PROTAC-based degraders, combination regimens, and ctDNA-guided monitoring, aiming to support precision oncology decision-making and improve long-term outcomes for patients with ALK-positive IMT.
2026-07-22 | Endobronchial mass in an adult: an unusual presentation of inflammatory myofibroblastic tumour.
Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, most commonly affecting children and young adults, with the lung being one of the the most common sites. Its variable clinical, radiological and pathological features often mimic malignancy, making diagnosis challenging. We report a middle-aged man in his early 50s presenting with life-threatening haemoptysis and found to have a right main bronchus mass causing central airway obstruction. Emergency rigid bronchoscopy with cryo-debulking was performed for airway stabilisation and tissue diagnosis. Histopathology confirmed IMT. Immunohistochemistry was anaplastic lymphoma kinase negative, while molecular analysis demonstrated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) positivity, highlighting the molecular heterogeneity of IMT. Following multidisciplinary tumour board discussion, the patient was initiated on targeted therapy with crizotinib, with planned reassessment for surgical resection. This case emphasises the importance of early tissue diagnosis, molecular profiling and multidisciplinary decision-making in achieving personalised and potentially lung-sparing treatment.
antibodies
2026-02-02 | Multifocal Inflammatory Myofibroblastic Tumor Presenting With Hemorrhagic Shock Due to Duodenal Invasion by a Pancreatic Head Mass: A Case Report.
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential. Although typically indolent, IMT can occasionally exhibit aggressive behavior, including distant metastasis or multifocal involvement. Clinical manifestations vary widely according to anatomic location. Gastrointestinal tract involvement has been reported; however, massive gastrointestinal bleeding leading to hemorrhagic shock is exceedingly rare. We present a 56-year-old man who presented with melena and hemorrhagic shock. Imaging demonstrated a pancreatic head mass with duodenal ulceration, along with a pulmonary nodule and multiple renal lesions. Endoscopic hemostasis was unsuccessful, and transcatheter arterial embolization (TAE) achieved temporary bleeding control. The patient subsequently underwent pancreaticoduodenectomy for definitive hemostasis and local disease management. Histopathologic examination of the pancreatic mass demonstrated spindle cell proliferation consistent with IMT and negative immunoreactivity for anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and other relevant markers. Systemic evaluation revealed multifocal disease involving the brain, parotid gland, lungs, heart, liver, pancreatic tail, kidneys, adrenal gland, lymph nodes, and bones. Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the parotid lesion showed gradual, continuous enhancement, consistent with a fibrous-rich lesion. Based on biopsies from multiple sites and the overall clinical course, a diagnosis of multifocal IMT was established. Initial systemic therapy with doxorubicin achieved stable disease at three months. Based on the genomic findings identified following comprehensive genomic profiling, the patient was subsequently enrolled in the DESTINY-PanTumor02 clinical trial and transitioned to treatment with trastuzumab deruxtecan targeting the human epidermal growth factor receptor 2 (HER2) alteration. Our case represents an exceptionally rare presentation of IMT, characterized by life-threatening gastrointestinal bleeding and extensive multifocal dissemination. It illustrates the marked radiologic and clinicopathologic heterogeneity of IMT and emphasizes the importance of comprehensive histopathologic and molecular evaluation to guide management in aggressive disease variants. Close collaboration across cross-disciplinary diagnostic specialties is essential for the assessment and treatment of rare, multi-organ conditions.
2025-11-24 | Unexpected complete resolution of intravesical inflammatory myofibroblastic tumor after immunotherapy for melanoma: A case report
Inflammatory myofibroblastic tumors (IMT) are exceedingly rare, particularly when originating in the bladder. Complete surgical resection is the gold standard treatment for IMTs. We describe a case of IMT of the urinary bladder that achieved complete radiographic and endoscopic resolution after systemic treatment with ipilimumab and nivolumab directed towards metastatic melanoma. This case is noteworthy due to the tumor's serendipitous and remarkable response to immunotherapy.
2025-10-23 | Fibroblasts in the tumor microenvironment: heterogeneity and dynamic interactions in tumor progression revealed by spatial transcriptomics.
Cancer-associated fibroblasts (CAFs) constitute the most abundant and functionally versatile stromal component of the tumor microenvironment (TME), with their phenotype and spatial location jointly governing tumor growth, immune evasion, metastasis, and therapeutic resistance. While traditional single-cell RNA sequencing has unveiled CAF transcriptional heterogeneity, it forfeits crucial tissue-contextual information; the advent of high-resolution spatial transcriptomics (ST)—encompassing platforms such as 10xVisium, Slide-seq, Stereo-seq, and MERFISH—now overcomes this limitation by preserving native tissue architecture while simultaneously capturing whole-transcriptome data and single-cell spatial coordinates, enabling comprehensive mapping of CAF “spatial atlases.” Recent literature has consolidated CAFs into five functional subtypes: myofibroblastic CAFs (myCAFs), inflammatory CAFs (iCAFs), antigen-presenting CAFs (apCAFs), matrix-remodeling CAFs (matCAFs), and proliferative CAFs (pCAFs), each exhibiting spatial preferences and dynamic plasticity within tumor cores, hypoxic niches, invasive fronts, and tertiary lymphoid structures. Distinct subpopulations form sub-micron-scale interaction networks with SPP1+ macrophages, CXCL13+ CD8+ T cells, natural killer cells, or endothelial cells to orchestrate either immune exclusion or activation. Multi-cancer investigations in colorectal, pancreatic, hepatic, and lung malignancies demonstrate that peri-tumoral enrichment of POSTN+ myCAFs predicts immune exclusion and shortened survival, whereas therapeutic targeting of CAF-immune or CAF-cancer signaling axes—such as IL-34/CSF1R, TGF-β/LOXL2, and JAG1/NOTCH1—can reverse immunotherapy resistance. Looking forward, integrative multi-omics, subcellular-resolution in-vivo tracking, and AI-driven spatial interaction modeling will further decode CAF spatial phenotypes and expedite their incorporation into precision oncology frameworks.
2025-09-16 | Primary Splenic Inflammatory Myofibroblastic Tumor, a rare Case and its Differential Diagnosis
Primary splenic inflammatory myofibroblastic tumor (PS-IMT) is very rare. We are reporting a case of PS-IMT in a 17-year-old female who presented with low-grade fever, weakness, and weight loss of three months’ duration. Radiological workup revealed a large, well-defined splenic mass lesion. Splenectomy was done, the histopathology of which revealed the diagnosis of PS-IMT. It is a tumor with indeterminate malignant potential, and its exact etiology remains unknown. It is primarily seen in children and young adults, but can occur at any age. Its clinical presentation is variable with no pathognomonic symptoms or signs. Radiologically, there is no characteristic appearance, and findings are usually nonspecific. Due to this, the diagnosis is often delayed. The primary treatment of PS-IMT is splenectomy. In unresectable and recurrent cases, corticosteroids and nonsteroidal anti-inflammatory drugs provide short-lived symptomatic benefit. Chemotherapy regimens based on anthracyclines and alkylating agents induce partial remission in some patients. Targeted therapy based on competitive inhibitors of ALK tyrosine kinase, like crizotinib, provides a more durable response in ALK-positive patients. There is a potential role of immunotherapy, especially in ALK-negative cases. The natural history of IMT is variable; the lesions may remain stable, progress slowly, or even spontaneously regress.
2025-08-20 | Treatment of Resistant TPM3::ALK + Fusion Protein Metastatic Inflammatory Myofibroblastic Tumor with ALK Targeting and Immune Checkpoint Inhibitor Combined Therapy
Background and Clinical Significance: Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms with low metastatic potential but a high recurrence rate. Approximately 60–80% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors (ALKis) a key therapeutic option. However, resistance to ALKis remains a significant clinical challenge, necessitating alternative treatment strategies. Case Presentation: We report the case of a 23-year-old woman diagnosed with a metastatic TPM3::ALK fusion-positive IMT, initially managed with crizotinib and ceritinib. Disease progression prompted a switch to alectinib, followed by lorlatinib in combination with immune checkpoint inhibitors (nivolumab + ipilimumab). The patient tolerated this regimen well, with manageable side effects, and has remained progression-free for over three years, demonstrating the potential efficacy of ALK-ICI combination therapy. Conclusions: This case highlights the rapid development of resistance to first- and second-generation ALKis and the emerging role of immune checkpoint inhibitors (ICIs) in IMT treatment. PD-L1 expression in ALK-positive IMTs suggests an immune escape mechanism, supporting combination ALK-ICI therapy as a viable approach. The successful long-term disease control achieved in this case underscores the importance of molecular profiling in guiding personalized treatment strategies for IMT. This report contributes to the growing body of evidence supporting precision medicine and immunotherapy in rare sarcomas.
other
2023-12-01 | Unraveling the Spectrum of Inflammatory Myofibroblastic Tumors in the Lung: A Comprehensive Case Series Highlighting Endobronchial, Pleural, and Lung Parenchymal Tumors
Diverse cases of inflammatory myofibroblastic tumors (IMTs) in the lung (pleural, endobronchial, and parenchymal) are presented while discussing the (preoperative) diagnostic challenges and treatment modalities. Other objectives include emphasizing the significance of gene rearrangements and highlighting the multidisciplinary approach in addressing IMTs. Four cases of IMT in the lung are presented, including a young adolescent girl with an ETV6-neurotrophic tyrosine receptor kinase 3 (NTRK3) gene rearrangement, a 5-year-old boy with challenging preoperative diagnosis, and 2 middle-aged women with respectively pleural and endobronchial tumors with one peribronchial relapse. The cases demonstrate the diverse clinical presentations and diagnostic complexities associated with IMT in the lung. Surgical resection remains the primary treatment modality, with complete resection leading to a cure in most patients. Unfortunately, aggressive relapse can occur, as in our last case of an endobronchial tumor. Frozen section may confirm the presence of malignant cells perioperatively and impact further treatment. The presence of gene rearrangements, such as ETV6-NTRK3, suggests potential therapeutic implications. Early detection and complete surgical removal of IMT are crucial for effective treatment. Identifying gene rearrangements such as ETV6-NTRK3 holds promise for targeted therapies. Diagnostic challenges, including the controversy of biopsies and preoperative evaluations, underscore the importance of a multidisciplinary approach. Anatomopathological recognition of IMT stays demanding. Close surveillance is necessary due to potential relapse, whereas frozen section perioperatively can help further treatment. This case series emphasizes the diagnostic challenges and therapeutic considerations for IMT in the lung.
proteins
2025-06-25 | Uterine Inflammatory Myofibroblastic Tumor Mimicking Myoma Treated With Gonadotropin-Releasing Hormone Therapy: A Case Report.
Inflammatory myofibroblastic tumors (IMTs) of the uterus are a rare entity that can be challenging to distinguish from leiomyomas, both radiologically and pathologically. No previous reports have documented the response of uterine IMT to gonadotropin-releasing hormone (GnRH) therapy. A 47-year-old Japanese woman presented to our hospital with excessive menstruation and uterine prolapse. Magnetic resonance imaging (MRI) revealed four well-demarcated uterine masses, with the largest measuring 81 mm. Myomas were suspected. Oral GnRH therapy was initiated to relieve the symptoms and reduce the preoperative volume. After four months, follow-up MRI showed a reduction in the largest mass to 62 mm and increased hyperintense areas on T2-weighted images. At six months, the patient underwent laparoscopic hysterectomy and colporrhaphy. Histopathological examination revealed that the largest tumor was an IMT with abundant myxoid matrix, positive for anaplastic lymphoma kinase (ALK), and ALK gene rearrangement. The remaining three masses were diagnosed as usual-type leiomyomas. This is the first reported case of uterine IMT treated with GnRH therapy, which resulted in notable tumor shrinkage. This case highlights both the potential therapeutic approach for uterine IMT and the diagnostic difficulty in distinguishing it from leiomyomas preoperatively.
2024-07-17 | Recurrent Inflammatory Myofibroblastic Tumor of the Larynx: Presentation and Management
Laser-assisted wide excision of the lesion was performed and since the lesion was confirmed during surgery to be attached to the left vocal process and arytenoid, an area more prone to frictional injury due to phonation, adjuvant treatment of botulinum toxin injection into the left thyroarytenoid muscle was performed.A total dose of 7.5 mu of botulinum toxin was injected during the surgery into the left thyroarytenoid muscle.Histopathological examination revealed a spindle cell tumor (Fig. 2) and immunohistochemistr y was positive for pan-cytokeratin (pan-CK), epithelial membrane antigen (EMA), smooth muscle actin (SMA), and in Ki-67 it showed 1-
2020-06-19 | Inflammatory Myofibroblastic Tumor of the Uterus
Inflammatory myofibroblastic tumors (IMT) of the uterus may be underrecognized as their morphology and immunophenotype may overlap with myxoid variants of uterine smooth muscle tumors and endometrial stromal tumors. Although ALK is a helpful biomarker, not all uterine IMTs are ALK -rearranged, and a small subset of myxoid leiomyosarcomas is ALK-positive. Herein, we evaluated a series of 23 IMTs for the novel endometrial stromal markers interferon-inducible transmembrane protein-1 (IFITM1) and BCOR, the novel myoid marker transgelin, and possible predictive markers p16 and p53 by immunohistochemistry to determine their expression profile and potential prognostic value. Patients’ ages ranged from 8 to 59 (mean 39) years and tumors from 2 to 20 (mean 8.2) cm. Follow-up was available for 12/23 (52%) patients; 9/12 (75%) without evidence of disease, 2/12 (17%) alive with disease, and 1/12 (8%) dead from disease. Four IMTs were classified as malignant due to extrauterine disease at diagnosis and/or recurrence. IFITM1 was positive (combined score>2) in 19/23 (83%), BCOR in 8/20 (40%), and transgelin in 22/23 (96%) of tumors. IFITM1 and BCOR were more often expressed in the myxoid component, and transgelin in the compact areas. p16 expression was absent in 5/23 (22%) of IMTs, while p53 was wildtype in all tumors. p16-negative IMTs included all 4 classified as malignant and one where the patient was lost to follow-up. Molecular data were available in 2 malignant IMTs, both of which harbored CDKN2A deletions. We conclude that caution is advised when using IFITM1, BCOR, and transgelin as markers for endometrial and smooth muscle tumors, as these are commonly expressed in IMTs. However, we did identify an association among lack of p16 staining, CKDN2A deletions, and aggressive behavior that merits corroboration by other studies. As a result of this finding, we recommend the use of p16 in the diagnostic work-up of uterine IMTs due to its potential prognostic significance.
2019-02-26 | Targeting ALK in Cancer: Therapeutic Potential of Proapoptotic Peptides
ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more. This makes ALK an attractive target for cancer therapy. Since ALK–driven tumors are dependent for their proliferation on the constitutively activated ALK kinase, a number of tyrosine kinase inhibitors have been developed to block tumor growth. While some inhibitors are under investigation in clinical trials, others are now approved for treatment, notably in ALK-positive lung cancer. Their efficacy is remarkable, however limited in time, as the tumors escape and become resistant to the treatment through different mechanisms. Hence, there is a pressing need to target ALK-dependent tumors by other therapeutic strategies, and possibly use them in combination with kinase inhibitors. In this review we will focus on the therapeutic potential of proapoptotic ALK-derived peptides based on the dependence receptor properties of ALK. We will also try to make a non-exhaustive list of several alternative treatments targeting ALK-dependent and independent signaling pathways.
2017-02-08 | Cytokine Interferon-γ suppresses the function of capsule myofibroblasts and induces cell apoptosis
ABSTRACT Myofibroblasts (MFs), a contractile subset of fibroblasts, play a pivotal role in physiological wound healing and in the development of many fibroconnective disorders. The complex cytokine network regulating the function of MFs in joint stiffness is still poorly understood. In this in vitro study, we investigated the effect of the cytokine Interferon‐gamma (IFN‐γ) on MFs isolated from human joint capsules. MFs were cultivated either in the presence of increasing concentrations of IFN‐γ alone or in combination with IFN‐γ neutralizing antibodies. Cell viability, cytotoxicity, apoptosis, and mRNA gene expression of the MF markers alpha‐smooth muscle actin (α‐SMA) and collagen type I were analyzed in MF cultures. Contraction potential was analyzed in an established collagen gel contraction assay simulating the extracellular matrix. Using immunofluorescence staining, we could verify that MFs express IFN‐γ‐receptor (R)‐1 on their membrane. IFN‐γ decreased MF viability and significantly elevated the apoptosis rate in a dose‐dependent manner. IFN‐γ down‐regulated α‐SMA and collagen type I mRNA expression which was associated with a diminished MF mediated contraction of the gel matrices. These effects were suppressed by simultaneous treatment of cells with a neutralizing IFN‐γ antibody. Our experiments confirm the hypothesis that the cytokine IFN‐γ is a crucial component of the regulatory network of capsule MFs. IFN‐γ notably influences the ability of MFs to contract collagen matrices by suppressing α‐SMA gene expression. IFN‐γ is toxic for MFs in high concentrations and may negatively regulate the number of pro‐fibrotic MFs during the healing process via induction of cell apoptosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2524–2533, 2017.
cell therapies
2023-10-30 | Heart Transplantation as a Treatment Option for Recurrent Myxofibrosarcoma: A Clinical Case.
Myxofibrosarcoma is one of the most rare tumors of the heart. Surgical resection is the principal method of treatment; however, in some cases, radical removal of the tumor is not possible. Here, we present a case of heart transplant in a patient who experienced recurrent myxofibrosarcoma of the left atrium and examine the morphological features of this tumor. A 40-year-old female patient presented for treatment for heart failure of a high functional class. An examination revealed a tumor in the left atrial cavity, which was subsequently surgically removed. Morphological examination revealed an inflammatory myofibroblastic tumor. After 2 years, the patient's tumor recurred. The tumor was removed, and a morphological study again diagnosed myxofibrosarcoma of the heart. A year later, recurrence was again diagnosed. Instrumental examination determined that the tumor had incurred into the mitral valve and possibly spread to the myocardium. Tumor resection was not possible, and the need to perform a heart transplant was determined. The given case contributes to the practical conclusion that heart transplant contributes to an increase in the life expectancy for patients with inoperable cases of cardiac sarcoma.
2023-09-28 | Flexible bronchoscope for the treatment of intratracheal inflammatory myofibroblastic tumor in children: a case report and literature review
Abstract Background Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor. In children, it most often occurs in the lung tissue and the trachea is rarely involved. Inflammatory pseudotumor is multifactorial in etiology and generally benign, but it is often mistaken for malignancy given its aggressive appearance. Although IMT is a benign tumor, it has the possibility of malignancy, recurrence and distant metastasis, and surgical resection is the first choice for its treatment. Case Presentation: we report a case of a 5-year-old boy with clinical symptoms of cough, wheezing, shortness of breath, and hemoptysis. Flexible bronchoscopy showed that the mass was obstructing the airway. The patient was diagnosed as anaplastic lymphoma kinase (ALK) positive IMT by pathological and immunohistochemical examination. After multiple times of flexible bronchoscopic cryotherapy under general anesthesia, the mass disappeared completely, and no recurrence was found in 6 years of follow-up. Conclusion IMT in the airway is rare in children and should be distinguished from asthma and other airway obstructive diseases when clinically encountered. The preferred treatment method is surgery. Children with simple IMT who are not suitable for surgery can choose bronchoscopic interventional therapy, which not only has high safety, but also reduces the risk and complications of surgery, and also reduces the financial burden of patients' families.
2023-04-20 | Liver transplantation for hilar inflammatory myofibroblastic tumor: Case report and review of the literature.
Inflammatory myofibroblastic tumors (IMTs) of the liver are rare neoplasms. These tumors are difficult to distinguish from other neoplasms by radiological examination, have uncertain evolution, and there is no consensus on the treatment of these lesions. Hilar tumors can involve the portal vein, hepatic artery, bile duct, and spread to the branches of the portal triad, causing obstructive symptoms, occlusive phlebitis, and portal hypertension. Thus, liver transplantation (LT) is an excellent alternative for locally advanced hilar tumors, since it ensures complete tumor resection with free margins. We present a literature review and a case report showing a 3-year-old boy with liver IMT invading the hepatic hilum and inferior vena cava, who underwent a successful living donor liver transplantation that required portal vein and vena cava replacement. The incidence of hilar IMTs is low and there is no well-established standard treatment. Liver transplantation for a hilar tumor with vascular invasion was acceptable in this case because the radically of the surgery was the key for the cure, and because the tumor was benign in nature.
2016-08-19 | The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation
State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.
2008-07-01 | Successful Orthotopic Heart Transplant in an Infant With an Inflammatory Myofibroblastic Tumor of the Left Ventricle
A female infant was diagnosed with an inflammatory myofibroblastic tumor involving the left ventricle, which compromised cardiac function. The tumor was endocardial in location and resection was not possible. In this study we report the first successful cardiac transplant and long-term follow-up for this indication. A female infant was diagnosed with an inflammatory myofibroblastic tumor involving the left ventricle, which compromised cardiac function. The tumor was endocardial in location and resection was not possible. In this study we report the first successful cardiac transplant and long-term follow-up for this indication.
small molecules
2026-08-13 | Gastric inflammatory myofibroblastic tumor in adults: a case report and literature review.
Gastric inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, with adult cases being particularly uncommon. We report a 64-year-old man with an incidentally detected gastric mass that was preoperatively suspected to be a gastrointestinal stromal tumor (GIST). The relevant literature on adult gastric IMT was also reviewed. Complete surgical resection with negative margins (R0 resection) remains the mainstay of treatment, whereas patients with confirmed ALK rearrangements may benefit from ALK inhibitor therapy. Histopathological confirmation and long-term surveillance are essential because of the potential for recurrence and occasional aggressive behavior.
2026-08-11 | Case Report: Dose-escalated volumetric modulated arc therapy achieving bowel and renal protection for large retroperitoneal inflammatory myofibroblastic tumor invading ureter and inferior vena cava
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm for which definitive radiotherapy in the retroperitoneum remains largely undefined, particularly when dose escalation must be balanced against the preservation of adjacent critical organs. A 59-year-old woman presented with a 10-day history of fever and abdominopelvic pain. Physical examination revealed deep tenderness in the right lower quadrant, and laboratory testing demonstrated leukocytosis. Imaging identified a 9.2 cm retroperitoneal mass invading the right ureter and inferior vena cava. Biopsy confirmed IMT, and capture-based next-generation sequencing revealed no class I actionable alterations. Given the unfavorable surgical anatomy and limited response to corticosteroids, curative-intent resection was precluded. The patient was treated with definitive dose-escalated volumetric modulated arc therapy (VMAT) employing a simultaneous integrated boost strategy (66 Gy/33 fractions to the boost volume and 50 Gy to the conventional planning target volume), with spatial sparing of adjacent organs at risk. Complete radiographic response was achieved at one month, without grade ≥2 treatment-related adverse events. At 19-month follow-up, the patient remained disease-free with stable renal function. This case demonstrates that dose-escalated VMAT with spatial organ avoidance can achieve durable complete remission in unresectable retroperitoneal IMT while preserving organ function, supporting its consideration as a curative-intent strategy in this challenging clinical setting.
2026-08-05 | Inflammatory myofibroblastic tumour: unravelling the interplay of inflammation, kinase signalling, and therapeutic resistance.
Inflammatory myofibroblastic tumour (IMT) is a mesenchymal tumour characterised by myofibroblastic cells and the presence of inflammatory cells, such as macrophages, neutrophils, and lymphocytes. IMT can originate from diverse anatomical locations within the body. The macrophage-rich immune microenvironment contributes to cytokine release and inflammation, but IMT is primarily driven by oncogenic alterations. Oncogenic fusions, most commonly involving anaplastic lymphoma kinase (ALK), and other genes, such as ROS1 and NTRK3, are seen in most IMTs. Upregulation of these genes activates downstream signalling pathways such as RAS/MAPK and PI3K/AKT, leading to uncontrolled cell proliferation. Constitutive tyrosine kinase activation disrupts cell-cycle control by suppressing p21/p27, inactivating Rb, and impairing p53-dependent checkpoints, thereby limiting apoptosis. Combining surgery with targeted kinase inhibitors remains the primary therapeutic approach, especially for ALK-positive IMT. On the contrary, ALK-negative IMT harbours distinct oncogenic fusions and is driven by diverse signalling pathways. Thus, it requires therapeutic methods targeting the specific molecular alterations. Resistance to ALK inhibitors can emerge during treatment. This resistance arises through bypass signalling, epigenetic changes, and secondary mutations. This review aims to analyse the interplay between inflammation and genetic fusions in the origin and progression of IMT. The review provides an overview of the therapeutic approaches currently in use, mechanisms of treatment resistance, and potential techniques to improve diagnosis and develop personalised therapeutic strategies.
2026-07-29 | Precision oncology for ALK positive inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with a broad clinical spectrum, ranging from indolent localized lesions to aggressive metastatic disease. Approximately half of IMTs harbor oncogenic anaplastic lymphoma kinase (ALK) gene fusions, which drive constitutive kinase activation and render the tumors sensitive to ALK tyrosine kinase inhibitors (ALK-TKIs). Although ALK-targeted therapy has significantly improved outcomes in IMT patients, durable responses are frequently limited by intrinsic and acquired resistance. In this review, we summarize the molecular taxonomy and functional stratification of ALK fusion variants in IMT, highlighting their diagnostic and therapeutic implications. We outline a tiered diagnostic workflow integrating immunohistochemistry, fluorescence in situ hybridization, and RNA-based next-generation sequencing to optimize fusion detection and guide precision treatment selection. We also discuss the major mechanisms of ALK-TKIs resistance—including on-target kinase domain mutations, off-target bypass pathway activation, and lineage plasticity—and propose corresponding clinical countermeasures. Finally, we review emerging therapeutic strategies such as third-generation ALK-TKIs, TRK-sparing brain-penetrant compounds, PROTAC-based degraders, combination regimens, and ctDNA-guided monitoring, aiming to support precision oncology decision-making and improve long-term outcomes for patients with ALK-positive IMT.
2026-07-22 | Endobronchial mass in an adult: an unusual presentation of inflammatory myofibroblastic tumour.
Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, most commonly affecting children and young adults, with the lung being one of the the most common sites. Its variable clinical, radiological and pathological features often mimic malignancy, making diagnosis challenging. We report a middle-aged man in his early 50s presenting with life-threatening haemoptysis and found to have a right main bronchus mass causing central airway obstruction. Emergency rigid bronchoscopy with cryo-debulking was performed for airway stabilisation and tissue diagnosis. Histopathology confirmed IMT. Immunohistochemistry was anaplastic lymphoma kinase negative, while molecular analysis demonstrated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) positivity, highlighting the molecular heterogeneity of IMT. Following multidisciplinary tumour board discussion, the patient was initiated on targeted therapy with crizotinib, with planned reassessment for surgical resection. This case emphasises the importance of early tissue diagnosis, molecular profiling and multidisciplinary decision-making in achieving personalised and potentially lung-sparing treatment.
antibodies
2026-02-02 | Multifocal Inflammatory Myofibroblastic Tumor Presenting With Hemorrhagic Shock Due to Duodenal Invasion by a Pancreatic Head Mass: A Case Report.
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential. Although typically indolent, IMT can occasionally exhibit aggressive behavior, including distant metastasis or multifocal involvement. Clinical manifestations vary widely according to anatomic location. Gastrointestinal tract involvement has been reported; however, massive gastrointestinal bleeding leading to hemorrhagic shock is exceedingly rare. We present a 56-year-old man who presented with melena and hemorrhagic shock. Imaging demonstrated a pancreatic head mass with duodenal ulceration, along with a pulmonary nodule and multiple renal lesions. Endoscopic hemostasis was unsuccessful, and transcatheter arterial embolization (TAE) achieved temporary bleeding control. The patient subsequently underwent pancreaticoduodenectomy for definitive hemostasis and local disease management. Histopathologic examination of the pancreatic mass demonstrated spindle cell proliferation consistent with IMT and negative immunoreactivity for anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and other relevant markers. Systemic evaluation revealed multifocal disease involving the brain, parotid gland, lungs, heart, liver, pancreatic tail, kidneys, adrenal gland, lymph nodes, and bones. Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the parotid lesion showed gradual, continuous enhancement, consistent with a fibrous-rich lesion. Based on biopsies from multiple sites and the overall clinical course, a diagnosis of multifocal IMT was established. Initial systemic therapy with doxorubicin achieved stable disease at three months. Based on the genomic findings identified following comprehensive genomic profiling, the patient was subsequently enrolled in the DESTINY-PanTumor02 clinical trial and transitioned to treatment with trastuzumab deruxtecan targeting the human epidermal growth factor receptor 2 (HER2) alteration. Our case represents an exceptionally rare presentation of IMT, characterized by life-threatening gastrointestinal bleeding and extensive multifocal dissemination. It illustrates the marked radiologic and clinicopathologic heterogeneity of IMT and emphasizes the importance of comprehensive histopathologic and molecular evaluation to guide management in aggressive disease variants. Close collaboration across cross-disciplinary diagnostic specialties is essential for the assessment and treatment of rare, multi-organ conditions.
2025-11-24 | Unexpected complete resolution of intravesical inflammatory myofibroblastic tumor after immunotherapy for melanoma: A case report
Inflammatory myofibroblastic tumors (IMT) are exceedingly rare, particularly when originating in the bladder. Complete surgical resection is the gold standard treatment for IMTs. We describe a case of IMT of the urinary bladder that achieved complete radiographic and endoscopic resolution after systemic treatment with ipilimumab and nivolumab directed towards metastatic melanoma. This case is noteworthy due to the tumor's serendipitous and remarkable response to immunotherapy.
2025-10-23 | Fibroblasts in the tumor microenvironment: heterogeneity and dynamic interactions in tumor progression revealed by spatial transcriptomics.
Cancer-associated fibroblasts (CAFs) constitute the most abundant and functionally versatile stromal component of the tumor microenvironment (TME), with their phenotype and spatial location jointly governing tumor growth, immune evasion, metastasis, and therapeutic resistance. While traditional single-cell RNA sequencing has unveiled CAF transcriptional heterogeneity, it forfeits crucial tissue-contextual information; the advent of high-resolution spatial transcriptomics (ST)—encompassing platforms such as 10xVisium, Slide-seq, Stereo-seq, and MERFISH—now overcomes this limitation by preserving native tissue architecture while simultaneously capturing whole-transcriptome data and single-cell spatial coordinates, enabling comprehensive mapping of CAF “spatial atlases.” Recent literature has consolidated CAFs into five functional subtypes: myofibroblastic CAFs (myCAFs), inflammatory CAFs (iCAFs), antigen-presenting CAFs (apCAFs), matrix-remodeling CAFs (matCAFs), and proliferative CAFs (pCAFs), each exhibiting spatial preferences and dynamic plasticity within tumor cores, hypoxic niches, invasive fronts, and tertiary lymphoid structures. Distinct subpopulations form sub-micron-scale interaction networks with SPP1+ macrophages, CXCL13+ CD8+ T cells, natural killer cells, or endothelial cells to orchestrate either immune exclusion or activation. Multi-cancer investigations in colorectal, pancreatic, hepatic, and lung malignancies demonstrate that peri-tumoral enrichment of POSTN+ myCAFs predicts immune exclusion and shortened survival, whereas therapeutic targeting of CAF-immune or CAF-cancer signaling axes—such as IL-34/CSF1R, TGF-β/LOXL2, and JAG1/NOTCH1—can reverse immunotherapy resistance. Looking forward, integrative multi-omics, subcellular-resolution in-vivo tracking, and AI-driven spatial interaction modeling will further decode CAF spatial phenotypes and expedite their incorporation into precision oncology frameworks.
2025-09-16 | Primary Splenic Inflammatory Myofibroblastic Tumor, a rare Case and its Differential Diagnosis
Primary splenic inflammatory myofibroblastic tumor (PS-IMT) is very rare. We are reporting a case of PS-IMT in a 17-year-old female who presented with low-grade fever, weakness, and weight loss of three months’ duration. Radiological workup revealed a large, well-defined splenic mass lesion. Splenectomy was done, the histopathology of which revealed the diagnosis of PS-IMT. It is a tumor with indeterminate malignant potential, and its exact etiology remains unknown. It is primarily seen in children and young adults, but can occur at any age. Its clinical presentation is variable with no pathognomonic symptoms or signs. Radiologically, there is no characteristic appearance, and findings are usually nonspecific. Due to this, the diagnosis is often delayed. The primary treatment of PS-IMT is splenectomy. In unresectable and recurrent cases, corticosteroids and nonsteroidal anti-inflammatory drugs provide short-lived symptomatic benefit. Chemotherapy regimens based on anthracyclines and alkylating agents induce partial remission in some patients. Targeted therapy based on competitive inhibitors of ALK tyrosine kinase, like crizotinib, provides a more durable response in ALK-positive patients. There is a potential role of immunotherapy, especially in ALK-negative cases. The natural history of IMT is variable; the lesions may remain stable, progress slowly, or even spontaneously regress.
2025-08-20 | Treatment of Resistant TPM3::ALK + Fusion Protein Metastatic Inflammatory Myofibroblastic Tumor with ALK Targeting and Immune Checkpoint Inhibitor Combined Therapy
Background and Clinical Significance: Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms with low metastatic potential but a high recurrence rate. Approximately 60–80% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors (ALKis) a key therapeutic option. However, resistance to ALKis remains a significant clinical challenge, necessitating alternative treatment strategies. Case Presentation: We report the case of a 23-year-old woman diagnosed with a metastatic TPM3::ALK fusion-positive IMT, initially managed with crizotinib and ceritinib. Disease progression prompted a switch to alectinib, followed by lorlatinib in combination with immune checkpoint inhibitors (nivolumab + ipilimumab). The patient tolerated this regimen well, with manageable side effects, and has remained progression-free for over three years, demonstrating the potential efficacy of ALK-ICI combination therapy. Conclusions: This case highlights the rapid development of resistance to first- and second-generation ALKis and the emerging role of immune checkpoint inhibitors (ICIs) in IMT treatment. PD-L1 expression in ALK-positive IMTs suggests an immune escape mechanism, supporting combination ALK-ICI therapy as a viable approach. The successful long-term disease control achieved in this case underscores the importance of molecular profiling in guiding personalized treatment strategies for IMT. This report contributes to the growing body of evidence supporting precision medicine and immunotherapy in rare sarcomas.
other
2023-12-01 | Unraveling the Spectrum of Inflammatory Myofibroblastic Tumors in the Lung: A Comprehensive Case Series Highlighting Endobronchial, Pleural, and Lung Parenchymal Tumors
Diverse cases of inflammatory myofibroblastic tumors (IMTs) in the lung (pleural, endobronchial, and parenchymal) are presented while discussing the (preoperative) diagnostic challenges and treatment modalities. Other objectives include emphasizing the significance of gene rearrangements and highlighting the multidisciplinary approach in addressing IMTs. Four cases of IMT in the lung are presented, including a young adolescent girl with an ETV6-neurotrophic tyrosine receptor kinase 3 (NTRK3) gene rearrangement, a 5-year-old boy with challenging preoperative diagnosis, and 2 middle-aged women with respectively pleural and endobronchial tumors with one peribronchial relapse. The cases demonstrate the diverse clinical presentations and diagnostic complexities associated with IMT in the lung. Surgical resection remains the primary treatment modality, with complete resection leading to a cure in most patients. Unfortunately, aggressive relapse can occur, as in our last case of an endobronchial tumor. Frozen section may confirm the presence of malignant cells perioperatively and impact further treatment. The presence of gene rearrangements, such as ETV6-NTRK3, suggests potential therapeutic implications. Early detection and complete surgical removal of IMT are crucial for effective treatment. Identifying gene rearrangements such as ETV6-NTRK3 holds promise for targeted therapies. Diagnostic challenges, including the controversy of biopsies and preoperative evaluations, underscore the importance of a multidisciplinary approach. Anatomopathological recognition of IMT stays demanding. Close surveillance is necessary due to potential relapse, whereas frozen section perioperatively can help further treatment. This case series emphasizes the diagnostic challenges and therapeutic considerations for IMT in the lung.
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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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