Case Of Inflammatory Myofibroblastic Tumor Research Articles

ALK Immunoexpression is Specific for Inflammatory Myofibroblastic Tumor Among Vulvovaginal Mesenchymal Neoplasms.

Gynecologic tract origin of inflammatory myofibroblastic tumor (IMT), a receptor tyrosine kinase fusion driven tumor with malignant potential, is uncommon and mostly involves the uterine corpus where misclassification as a smooth muscle tumor may occur due to overlapping morphologic features. With rare exception, uterine IMT involves ALK rearrangements and exhibits ALK immunoexpression. Molecularly confirmed vulvovaginal IMT has not been reported, but several low-grade mesenchymal tumors in this region exhibit myxoid stroma and/or inflammatory infiltrates that may resemble IMT. The aims of this study were to define the diagnostic specificity of ALK immunoexpression for IMT among a broad spectrum (107 cases) of vulvovaginal mesenchymal tumors in the differential diagnosis of IMT and to report the clinicopathologic features of vulvovaginal IMT identified in our archives or via retrospective ALK staining of otherwise classified vulvovaginal tumors. Review of archives from 5 different centers revealed a single case of vulvar IMT in a 62-yr-old woman. The 2.5 cm well-circumscribed tumor exhibited the typical microscopic features of IMT, namely a loose fascicular distribution of bland spindle cells within a myxoid stroma, accompanied by an infiltrate of plasma cells, lymphocytes, and eosinophils. The tumor cells exhibited expression for smooth muscle actin, desmin, h-caldesmon, and ALK. Break-apart fluorescence in situ hybridization confirmed the presence of ALK rearrangement. The patient did not receive any treatment and is alive without disease 32 mo later. No evidence of ALK expression was detected in any of the other 107 vulvovaginal tumors, which included 14 aggressive angiomyxomas, 2 superficial angiomyxomas, 12 angiomyofibroblastomas, 8 cellular angiofibromas, 15 smooth muscle neoplasms, 10 peripheral nerve sheath tumors, 20 fibroepithelial polyps, and a variety of other low grade mesenchymal tumors. Although vulvovaginal ALK- rearranged IMT is exceedingly rare, the behavior remains to be fully understood. ALK immunohistochemistry, which appears specific for IMT in this anatomic site, is advised in the evaluation of vulvovaginal mesenchymal tumors exhibiting myxoid stroma and/or an inflammatory infiltrate.

Renal inflammatory myofibroblastic tumour presenting with a large retroperitoneal abscess

Inflammatory myofibroblastic tumour arising from the kidney is a rare occurrence. In this case report, we present a rare case of inflammatory myofibroblastic tumour arising from the kidney diagnosed after the presentation with a large retroperitoneal abscess for the first time in literature. A 55-year-old woman with diabetes mellitus presented to us with painful lump in the left lumbar region of the back for 1-week duration. On examination, there was a firm, diffuse lump in the left lumbar region of the back. Her inflammatory markers were high, but the serum creatinine and blood urea were within the normal range. Abdominal ultrasonography showed a distorted left kidney with a heterogeneous mass consisting cystic and solid components measuring approximately 7 × 9 × 8 cm in size. A contrast-enhanced computed tomography scan showed an 11 × 9 × 9 cm-sized low-density mass posterior to the left kidney with multiple contrast-enhancing septations which appeared posterior to but separate from the left kidney within the left renal fascia. There was breeching of the Gerota’s fascia with extension posteriorly up to subcutaneous tissue. Since the radiological opinion was in favour of a complex perinephric abscess, open drainage of the abscess was performed after failed attempts of ultrasound-guided drainage. The biopsy of the abscess wall was suggestive of a renal cell carcinoma and radical nephrectomy was planned. Due to tumour invasion, the radical nephrectomy was combined with a splenectomy and the specimen sent for histology. It showed an inflammatory myofibroblastic tumour or pseudotumour with the periphery showing ulceration and abscess formation. The patient had an uneventful recovery following surgery. Thus, we report the first case of renal inflammatory myofibroblastic tumour presenting with a large retroperitoneal abscess extending to the subcutaneous tissue plane. Final diagnosis was made only after radical surgery which was curative.

Pulmonary inflammatory myofibroblastic tumor in a breast cancer patient, a rare presentation

Inflammatory myofibroblastic tumor (IMT), a benign and rare neoplasm, of mesenchymal origin, pseudoarcomatous, is responsible for about 0.7% of all neoplastic presentations in the pulmonary region, being the most frequent cause of pulmonary nodules in pediatric patients, approximately 50% of the presentations. Thus, the present study aims to report a rare case of IMT in the lung site in a 31-year-old patient undergoing treatment for breast cancer, according to a literary review, relating the data according to the clinical presentation. Due to scarce documentation in the medical literature, no cases were found similar to the one described in relation to the reported oncological primary condition of the patient, making the present case a clinical challenge in modern medical practice.

Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents.

Inflammatory myofibroblastic tumors (IMT) are rare, intermediate malignant tumors harboring frequent somatic molecular rearrangements. The management of IMT has not been standardized. A retrospective multicenter study was conducted on all pediatric patients treated for IMT between 2000 and 2019. This series included 39 cases of IMT, with a median age at diagnosis of 7years (range 20days to 16years). Tumor location included pelvis-abdomen (n=16), thorax (n=14), head and neck (n=7), and limbs (n=2). One patient had metastatic disease. Immunochemistry showed 21/39 (54%) anaplastic lymphoma kinase (ALK)-positive tumors. Somatic tyrosine kinase rearrangement was present in 31/36 (86%) of the tumors analyzed: 21 ALK, five ROS1, and five NTRK. Immediate surgery was performed in 24 patients (62%), with adjuvant therapy for three patients. Delayed surgery after neoadjuvant therapy was possible in 10 cases. Exclusive systemic therapy was delivered to four patients; one patient with orbital IMT was managed by watchful waiting. After a median follow-up of 33months (range 5-124), eight (20%) recurrences/progressions occurred after surgery (seven after primary surgery and one after delayed surgery), after a median interval of 7months (range 2-21), all in thoracic locations. The 3-year overall and disease-free survivals were 96.8% (95% CI: 79.2%-94.0%) and 77.4% (95% CI: 59.6%-88.1%), respectively. Relapses/progressions were more common in patients with a thoracic primary (p<.001) or after incomplete surgery with no adjuvant therapy (p=.027). Surgery is effective in most cases of pediatric IMT. Systematic analysis of tyrosine kinase rearrangement is recommended. When the tumor is deemed only partially resectable to preserve organs and function, neoadjuvant therapy may be proposed to allow adequate conservative surgery.

Inflammatory myofibroblastic tumors of the urinary bladder: a clinicopathological study of ten cases

0bjective To investigate the clinicopathological features,immunohistochemical phenotypes, molecular genetic alterations,diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT) of the urinary bladder. Methods: Ten cases of IMT of the urinary bladder (three cases at Ningbo Diagnostic Pathology Center from September 2011 to December 2020, five in-house diagnosed cases and two consultation cases at Shanghai Rui Jin Hospital from June 2011 to December 2020) were collected retrospectively. The clinicopathologic features and immunophenotypic profiles were studied by light microscopy and immunohistochemistry (EnVision method). The translocation of ALK gene was detected by fluorescence in situ hybridization (FISH). Results: Of the 10 patients, eight were male and two were female. The patients' age range was 16 to 62 years (median 36 years).The main clinical presentation was hematuria and urinary irritation. Three cases were located at the dome of the urinary bladder, four cases were in the left lateral wall and the remaining three cases were in the right lateral wall. The tumor size ranged from 1.5 cm to 8.5 cm. In eight cases, the tumors were mainly submucosal, and in some cases extending to the muscular layer of the urinary bladder. In two cases, the tumors were mainly located in the muscular layer and focally extended to the submucosa and adventitia. Histologically, four cases had the nodular fasciitis-like pattern, three cases had fibrohistiocytoma-like pattern, two cases had mixed histologic patterns and the remaining case showed leiomyosarcoma-like histologic features. Immunohistochemically, the tumor cells expressed SMA (10/10),calponin (9/10),desmin (6/10) and CKpan (9/10). Cytoplasmic staining for ALK1 and ALK (5A4) was detected in 7 of 10 cases and 8 of 10 cases, respectively. Nuclear and cytoplasmic staining for ALK (D5F3) was detected in 7 of 10 cases. Among eight cases with material available for FISH analysis, ALK rearrangement was present in five cases. Follow-up data were available in eight patients and none had local recurrence nor distant metastasis. Conclusion: IMT of the urinary bladder is an uncommon mesenchymal neoplasm with intermediate malignant potential.It has special clinicopathologic features, and a minority of cases have local tumor recurrence.

Inflammatory Myofibroblastic Tumor of Digestif Truct: Three Case Reports

Inflammatory myofibroblastic tumors (IMT) are a rare soft tissue and viscera neoplasm with unknown etiopathogeny. They were first described in the lung, with a wide range of synonyms. They can invade adjacent organs, recur after excision or give distant metastases. The debate persists about their inflammatory or tumor, benign or malignant nature. On the radioclinical funding, they can mimic a malignant neoplasm. The diagnosis is almost always made on the pathological examination. The treatment is poorly codified but the management is usually surgical. These tumors rarely affect the digestive truct. The only cases of gastrointestinal IMT in adults, at Hassan II university hospital in Fez during last 15 years, are those presented in this article

A case of inflammatory myofibroblastic tumor in the floor of the mouth

A case of inflammatory myofibroblastic tumor in the floor of the mouth

Unusual diagnosis in a patient presenting with fever and bilateral lung infiltrates.

Inflammatory myofibroblastic tumour (IMT) is a rare neoplasm, most commonly described in children and young adults. We present a case of IMT in an elderly man. https://bit.ly/355wf8X

Cervical Sympathetic Trunk-Centered Inflammatory Myofibroblastic Tumor Complicated with Postoperative First Bite Syndrome

Inflammatory myofibroblastic tumors (IMTs) in the head and neck region are common, but those with sympathetic trunk involvement are extremely rare. Here we present a case of cervical sympathetic trunk-centered IMT which is also accompanied by ipsilateral carotid artery, internal jugular vein, and vagus nerve involvement. The patient initially complained of an episodic painful swelling on the right side of the neck and underwent surgery. Preoperative and postoperative serum IgG4 level during 3-year follow-up time is within normal limits. Immunohistochemical study of the tumor has also revealed negativity to IgG4. Postoperative first bite syndrome (FBS) was observed. Surgery seems to be first-line therapy in the patient with IgG4-negative IMT.

Inflammatory myofibroblastic tumor of head of pancreas in a 5 Year-Old child

Inflammatory myofibroblastic tumor (IMT) is assumed as a rare benign tumor that can appear in various organs. Since Umiker et al. introduced inflammatory pseudotumors for the first time in 1954, it was found that occurrence in the head of pancreas is very rare (Baião et al., 2019) [1]. Differentiating non-neoplastic lesions of pancreas from adenocarcinoma remains a challenge despite advances in diagnostic modalities whereas cystic and solid lesions and some normal anatomic variants can mimic malignancy (Okun and Lewin, 2016 Jan 1) [2]. Histologic patterns of IMT can be identified as fibroblastic and myofibroblastic proliferation with inflammatory infiltrate. They are more common in Women and peak of occurrence is between 2 and 16 years of age (Mirshemirani et al., 2011) [3]. In head of pancreas the disease can present with obstructive jaundice and the key for diagnosis is having a tissue specimen by means of needle biopsy. Though in all reported cases surgery is suggested as the lone treatment option, its natural history is obscure still and there can be a challenge in its treatment and also the extent of surgery. Here a new case of IMT of head of pancreas is reported.

Lung cancer mimickers - a case series of seven patients and review of the literature.

Background: Lung is the third most frequent identified site of malignancy and lung cancer is the most lethal type of cancer in the world. Several benign lung diseases or proliferations may mimic lung carcinoma in its clinical, pathological, and radiological presentation, which makes the differential diagnosis life changing. This case series was designed to describe the main diagnosis encountered in a multidisciplinary emergency hospital during the last years in Romania. Results: The most challenging cases encountered during the recent years were those of lung hamartoma associated with eosinophilic pneumonia because of the multicentricity of the disease and the suspicion for metastasis in the clinical setting, pulmonary aspergillosis that presented as a cystic lesion with a 9 mm mural nodule, actinomycosis discovered as firm nodule showing aspects of false pleural invasion, cryptococcosis – a hilar mass for which a pneumectomy was prepared, pulmonary parasitosis that presented as a nodule with irregular borders, causing pleural retraction, one case of inflammatory myofibroblastic tumor of the lung, one case of tumorlet type neuroendocrine lesion in a patient with history of melanoma and renal oncocytoma, admitted under the suspicion of lung metastasis. Conclusions: These are some of the main mimickers of primary or secondary lung cancers and one must be aware of these similitudes to avoid higher cost procedures, psychological stress for the patient and higher mortality.

Clinicopathological features of inflammatory myofibroblastic tumor

Objective: To investigate the clinicopathological diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT). Methods: Thirty-two cases of IMT collected at the People's Hospital of Jiangsu Province from May 2010 to May 2020 were evaluated for their clinical, histologic, immunohistochemical and genomic features, and relevant literature was reviewed. Results: There were 19 male and 13 female patients, with age ranging from 5 to 65 years (mean, 37 years). The tumors were located in the lung and mediastinum (10 cases), gastrointestinal tract and mesentery/omentum (12 cases), urinary bladder (5 cases), head and neck (3 cases), somatic soft tissue (1 case), and retroperitoneum (1 case). Four cases of epithelioid inflammatory myofibroblastic sarcoma (EIMS) were all located intra-abdominally. Histologically, the tumor cells were myofibroblasts and fibroblasts arranged in predominantly fusiform pattern, with variably edematous to myxoid background or sclerotic collagenized stroma, and variably mixed chronic or acute inflammatory cells infiltration. EIMS were composed mainly of epithelioid tumor cells, with myxoid stroma and numerous neutrophils. Immunohistochemically, the tumor cells expressed cytoplasmic ALK (25/32, 78%), whereas the four EIMS showed nuclear membrane ALK staining pattern. The tumor cells also expressed CKpan (8/19), SMA (24/32, 75%) and desmin (12/32, 38%); all four EIMS also showed strong positivity for desmin. Fluorescence in situ hybridization (FISH) for ALK gene rearrangement showed split apart signals in 12 of 15 cases, most commonly with atypical signals. Next-generation sequencing (NGS) was performed in three tumors and showed that one case of lower leg IMT harbored a novel CLIP2-ALK fusion, and two cases of EIMS harbored RANBP2-ALK fusion. Follow-up data were available in 29 patients. Twenty-two patients were alive with no evidence of tumor, four patients had tumor recurrences (three patients were treated with crizotinib and were alive with tumor), and three patients died of the disease (including two patients with EIMS). Conclusions: IMTs show a wide morphologic spectrum, and should be differentiated form a variety of benign or malignant tumors. Immunohistochemistry (ALKp80, ALKD5F3) and FISH (ALK break-apart probe) could assist the diagnosis of IMT, with NGS recommended for the atypical cases.

Inflammatory Myofibroblastic Tumor After Treatment of Wilms Tumor in a 6-Year-Old Boy: A Case Report and Literature Review

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with an indolent course. It is less often reported as a second tumor that occurs after treatment of malignant tumors in pediatric patients. Here, we report a case of IMT following Wilms tumor (WT), and conduct a literature review concerning IMTs and WT to evaluate the diagnostic possibility of IMT as a second tumor. The coexistence of the 2 tumors may cause confusion as to whether they share genetic links or that IMTs may appear as late effects of the treatment of WT.

Clinical characteristics and outcomes of 17 cases of inflammatory myofibroblastic tumor at a University Hospital in China.

The aim of the present study was to explore the clinical and pathological characteristics, diagnosis, and treatment of inflammatory myofibroblastic tumor (IMT). A total of 17 patients with IMT diagnosed between July 2010 and February 2020 were included in the present study, and the clinical characteristics, pathological features, treatment and prognosis were analyzed retrospectively. The cohort consisted of 17 participants, including 12 men and 5 women, with a mean age of 34.76 years. The most common locations of tumors were the bronchi and the lungs (9 cases, including 1 case involving the mediastinum), followed by the colon and bladder (2 cases each), and the omentum majus, mesocolon, stomach and peritoneal cavity (1 case each). Immunohistochemical staining demonstrated that the tumor cells exhibited positive staining for anaplastic lymphoma kinase p80 (13/17), smooth muscle actin (12/17), cytokeratin pan (6/17), vimentin (5/17) and desmin (4/17). The follow-up time was 18–114 months. A patient with epithelial inflammatory myofibroblast sarcoma (EIMS) succumbed to the disease, 1 case was lost to follow-up, 2 cases relapsed and the other 13 cases were considered cured. IMTs may be malignant or low-grade. EIMS is a rare and invasive variant of IMT. The clinical and imaging manifestations are often unique and vary among individuals. Once confirmed by pathology, radical surgery should be the first choice of treatment.

A Rare Case of Inflammatory Myofibroblastic Tumour in a young Female Presenting with Pancoast Tumour of Left Lung

A Rare Case of Inflammatory Myofibroblastic Tumour in a young Female Presenting with Pancoast Tumour of Left Lung

Infantile Inflammatory Myofibroblastic Tumor of Spleen

Background: Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm with unknown etiology and recurrent potential. They are widely reported in children and young adults. Nearly 50% of inflammatory myofibroblastic tumor harbor rearrangement in anaplastic lymphoma kinase (ALK) gene with the majority expressing ALK protein. ALK-negative IMTs harbor alteration in ROS1 gene in a subset of cases. Few reports have shown association of IMT with Epstein–Barr virus (EBV). Case report: We report a case of IMT of the spleen in an 18-month-old infant presenting with abdominal distention and failure to thrive. Workup for ALK-1, ROS1, and EBV small-encoded RNA in-situ hybridization using immunohistochemistry was negative. Conclusions: IMT can arise in an infant spleen.

A NOVEL TREATMENT APPROACH FOR A RARE TRACHEAL TUMOR

SESSION TITLE: Fellows Procedures Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: The differential diagnosis for tracheal tumors is broad and often requires direct endobronchial evaluation for management. Neoplastic tumors account for 10% of tracheal masses. Herein, we describe a rare adult tracheal tumor that was successfully treated bronchoscopically. CASE PRESENTATION: A 48 year-old non-smoking female with childhood asthma presented to pulmonary clinic with a chronic cough for 4 months despite multiple courses of antibiotics and steroid bursts for suspected bronchitis. Due to persistent symptoms, she ultimately underwent a computed tomography scan of the chest which revealed a 0.9x0.6x0.5 cm polypoid-like density at the tracheal carina. Initial endobronchial biopsies showed inflammatory cells without evidence of malignancy. Due to concern for sampling artifact, she underwent a flexible/rigid bronchoscopy with tumor excision by snare electrocautery, argon plasma coagulation, and cryotherapy. Pathologic examination revealed an inflammatory myofibroblastic tumor (IMT) without an ALK rearrangement. A tumor board recommended curative tracheal resection versus surveillance bronchoscopy and imaging. The patient opted for surveillance as her symptoms had resolved. She has had annual bronchoscopies without any evidence of recurrence, and she remains asymptomatic. DISCUSSION: IMTs are slow growing quasi-neoplastic lesions that mostly affect children under 16 years old and are rarely reported in adults, accounting for 0.04-0.07% of all lung neoplasms. Most commonly affecting the lungs, these tumors can also involve a multitude of different organs. The etiology remains unknown although it is theorized to arise from an inflammatory process like a prior infection, trauma or surgery. However, the ALK rearrangement, which has been noted in 50% of IMTs, suggests a possible neoplastic origin. Classic pathologic features include myxoid spindle myofibroblasts with abundant inflammatory cells of plasma cells, lymphocytes, and eosinophils. Up to 80% of patients are asymptomatic but few may present with symptoms suggestive of, and commonly mistaken for, asthma. IMT treatment typically requires surgical resection via thorascoscopy or thoractomy. Chemotherapy, ALK directed therapies, and/or steroids have been used in nonsurgical cases. Few case reports have described effective bronchoscopic resection. A case series of 7 patients reported successful resection with one recurrence. Unfortunately, due to the tumor’s rarity, no robust studies exist for evaluating bronchoscopic treatment. A bronchoscopic approach offers a minimally invasive and potentially curative option but requires regular follow up for recurrence. CONCLUSIONS: IMTs are rare adult tracheal tumors, and treatment often entails surgical tracheal resection, which carries significant peri-operative risks with prolonged recovery. This case of IMT was successfully treated by bronchoscopic resection with curative effect. Reference #1: Jain S, Chopra P, Agarwal A, et al. Inflammatory myofibroblastic tumor of trachea. J Bronchol Intervent Pulmonol 2013;20:80-83. Reference #2: Oztuna F, Pehlivanlar M, Abul Y, et al. Adult inflammatory myofibroblastic tumor of the trachea: case report and literature review. Respir Care 2013;58:e72-6. DISCLOSURES: Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by Tao He, source=Web Response No relevant relationships by Leeyen Hsu, source=Web Response No relevant relationships by Scott Oh, source=Web Response

Inflammatory myofibroblastic tumors associated with the placenta: a series of 9 cases

Inflammatory myofibroblastic tumors (IMTs) of the uterus are often associated with pregnancy and are delivered with the placenta. We describe the clinical, pathologic, and molecular findings in nine cases of placenta-associated IMT (PaIMT). All the lesions were incidentally discovered at delivery or on placental pathological examination. The maternal age ranged from 21 to 41 (mean = 30.6) years. Eight patients had high-risk pregnancies, and when known, all patients were multigravida. Macroscopically, eight tumors were well defined, ranging in size from 2 to 6cm present at the maternal surface of the placenta (n=3) and membranes (n=4) or separately delivered with the placenta (n=2). All nine lesions revealed classical IMT morphology with spindle cells associated with a lymphoplasmacytic infiltrate and thin elongated vessels. Five showed decidualization, and five showed coagulative necrosis. All tumors expressed CD10. Of the seven tumors that were anaplastic lymphoma kinase (ALK) positive, six were confirmed to have an ALK rearrangement by fluorescence in situ hybridization (FISH), whereas one failed FISH testing. Fusions included TIMP3-ALK (n=3), THBS1-ALK (n=2), and a novel SYN3-ALK fusion (n=1). Clinical follow-up was available in three patients, with no recurrence reported. There appears to be an increased frequency of uterine IMTs in pregnancy and associated with the placenta. No PaIMT has behaved aggressively, although follow-up has been quite limited. This may speak to a specific behavior of these tumors when associated with pregnancy.

Characteristic Of Inflammatory Myofibrinoblastic Tumor: Retrospective Analysis Of 4 Cases In Children Hospital Number 2

Introduction: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that involves various organs. Surgery is the mainstay of therapy for this tumor. Approximately half of all IMT cases have anaplastic lymphoma kinase (ALK) rearrangements; therefore, the ALK inhibitor crizotinib is suggested as a promising treatment for unresectable cases with ALK rearrangements. In cases withoutALK rearrangement, chemotherapy is an alternative treatment for unresectable tumors. Cases report: We report 4 cases of IMT treated in Children Hospital Number 2 since 2018. There was one case with mesenteric tumor, one with perineal tumor detected at birth, one with inferior mediastinal tumor and one with intestinal tumor. We evaluated ALK expression by immunohistochemistry and ALK rearrangement by fluorescence in situ hybridization (FISH) in 3 cases and all negative. Treatments included tumor resection or biopsy and chemotherapy with methotrexate (30mg/m2) day 1 and vincristine (1.5mg/m2) day 1 and 7 in a 3 week cycle together with NSAID or steroid for inflammatory control. There was one case with complete response to surgery and chemotherapy; the other 3 cases ended in death due to tumor recurrence (3 cases) and metastasis (1 case). Conclusions: IMT has a diverse clinical presentation, appears in many different locations, and the clinical course can progress quickly with high rate of recurrence after incomplete surgical resection. Surgery is the optimal approach, but in those without complete resection and in those with tumor progression, tyrosine kinase inhibition should be considered if there is ALK rearrangement. In the absence of ALK rearrangement, additional tyrosine kinase rearrangements and other potentially efficacious chemotherapy regimens need to be studied for these patients.

Abstract 3191: Detection of molecular drivers in inflammatory myofibroblastic tumor: study on archival tissue from EORTC 90101 “CREATE” phase II clinical trial

Abstract Background. Inflammatory myofibroblastic tumor (IMFT) is a rare mesenchymal neoplasm, mainly driven by anaplastic lymphoma kinase (ALK) rearrangement, which is present in 50% of cases and target for ALK inhibition. For the current project we used tumor material from IMFT patients treated with the ALK/ROS1/MET inhibitor crizotinib in the frame of EORTC 90101, where IMFT patients were attributed to ALK+/- sub-cohorts based on the presence (&amp;gt;15% of cells) or absence (&amp;lt;15%) of ALK rearrangement by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC) [Schöffski at al. Lancet Respir Med. 2018]. The aim of the project was to evaluate the frequency of ALK rearrangement, compare different methods of ALK detection, perform a detailed characterization of ALK rearrangement partners, and to identify other potential molecular drivers with potential pharmacodynamic relevance. Material and Methods. Archival material from 24 IMFT cases, both primary or metastatic samples, was analyzed by IHC using ALK antibodies: ALK1 (DAKO) and ALK-D5F3 (Cell Signalling), and pan-NTRK (Ventana, clone EPR17341). ALK and ROS1 rearrangement were studied by FISH and fusion genes were detected using the Archer CTL Fusion Panel. Results. ALK immunopositivity by ALK1 and ALK-D5F3 was observed in 14 out of 24 cases and 11/21, respectively. ALK rearrangement by FISH was found in 13/23 samples. With Archer, fusion transcripts were identified in 13/20 specimens, all but one involving ALK with 11 different fusion partners. In one case we detected an ETV6-NTRK3 fusion; NTRK positivity was confirmed by IHC. Interestingly, the NTRK fusion case responded to crizotinib, which shows cone anti-NTRK activity [Okamura et al. JCO Precis Oncol 2019]. We did not detect ROS1 rearrangement by FISH in any sample. Two samples with ALK rearrangement by Archer were negative by FISH, with 11% and 0% of cells with ALK split signal, but both showed protein expression with both antibodies used. They responded to crizotinib with either a RECIST 1.1 complete response or stable disease, for 43 and 9 months, respectively. All but one case with ALK rearrangement by Archer were positive by ALK IHC with ALK1 antibody. The only immunonegative sample had an EML4-ALK1 fusion. Two cases were positive with ALK-D5F3 antibody but no ALK positivity was detected using ALK1, and no ALK rearrangement was detected by FISH or Archer panel, suggesting false positive results. Conclusions. ALK rearrangement is the most common driver in IMFT and the fusion can involve multiple partners. ALK1 but not the ALK-D5F3 antibody shows high ALK specificity in IMFT. The Archer CTL Fusion panel is a reliable and sensitive method for detecting fusion transcripts in IMFT, also allowing to detect alternative fusion genes, which may be responsible for the sensitivity to kinase inhibitors. Citation Format: Agnieszka Wozniak, Che-Jui Lee, Tom van Wezel, Jozef Sufliarsky, Hans Gelderblom, Jean-Yves Blay, Maria Debiec-Rychter, Raf Sciot, Judith V.M.G. Bovee, Patrick Schöffski. Detection of molecular drivers in inflammatory myofibroblastic tumor: study on archival tissue from EORTC 90101 “CREATE” phase II clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3191.