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Smaldone MC, Pizzicato P, Cariello V, Baldari D, Rossi A, Pirisi P, Capasso M, Ruotolo S, Capozza MA, Errico ME, Bifano D, Minelli R, Baldazzi M, Paviglianiti G, Napolitano M, Rossi E. Mesenteric inflammatory myofibroblastic tumor (IMT), a rare neoplasm in a pediatric patient: imaging findings and literature review. J Ultrasound 2025; 28:159-166. [PMID: 39951241 PMCID: PMC11947368 DOI: 10.1007/s40477-025-00994-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 01/23/2025] [Indexed: 03/28/2025] Open
Abstract
Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms commonly classified as having "intermediate malignancy" due to their unique clinical, pathological, and molecular features. These tumors can exhibit aggressive biological behavior, including local invasion, recurrence, and, on rare occasions, distant metastasis. IMTs may arise in various anatomical locations, with the lung, mesentery, and omentum being the most frequent sites. Although IMTs can occur at any age, they are more commonly diagnosed in children and young adults. Their clinical manifestations and imaging findings are often nonspecific and may resemble malignant pathology, making diagnosis challenging. Moreover, the histopathological characteristics of IMTs can overlap with those of other conditions. In this report, we present a case of multicentric abdominal IMT in a pediatric patient and review the imaging features of abdominal IMTs in children, as documented in the limited number of available cases. Accurate differential diagnosis requires a comprehensive understanding of both the clinical presentation and radiographic features of these tumors. Radiologists should be familiar with the distinctive imaging characteristics of IMTs to ensure that this rare pathology is considered in the differential diagnosis of any abdominal mass in pediatric patients.
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Affiliation(s)
| | - Paolo Pizzicato
- Department of Radiology, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy.
| | - Valentina Cariello
- Dipartimento Di Medicina Di Precisione, Università Degli Studi Della Campania "L. Vanvitelli, Piazza Luigi Miraglia 2, Naples, Italy
| | - Diana Baldari
- Department of Radiology, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
| | - Antonio Rossi
- University "Campus Biomedico", Via Álvaro del Portillo 21, 00128, Rome, Italy
| | - Pietro Pirisi
- UOSD Chirurgia Pediatrica Oncologica, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
| | - Maria Capasso
- UOC Oncologia Pediatrica, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
| | - Serena Ruotolo
- UOC Oncologia Pediatrica, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
| | | | - Maria Elena Errico
- UOC Anatomia Patologica, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
| | - Delfina Bifano
- UOC Anatomia Patologica, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
| | - Rocco Minelli
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via Francesco De Sanctis 1, Campobasso, Italy
| | - Michelangelo Baldazzi
- Pediatric and Adult CardioThoracic and Vascular, Oncohematologic and Emergency Radiology Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy
| | - Giuseppe Paviglianiti
- Sezione Di Scienze Radiologiche, Dipartimento Di Biomedicina, Neuroscienze E Diagnostica Avanzata (BIND), University of Palermo, Via del Vespro 129, Palermo, Italy
| | - Marcello Napolitano
- Department of Paediatric Radiology and Neuroradiology, V. Buzzi Children's Hospital, 32 Castelvetro St, Milan, Italy
| | - Eugenio Rossi
- Department of Radiology, AORN "Santobono-Pausilipon", Via Posillipo 226, Naples, Italy
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Zhu X, Dong X, Sheng H, Deng R, Duan X. Inflammatory myofibroblastic tumor of the right renal pelvis: A case report. Urol Case Rep 2025; 59:102969. [PMID: 39995766 PMCID: PMC11849649 DOI: 10.1016/j.eucr.2025.102969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 01/21/2025] [Accepted: 01/28/2025] [Indexed: 02/26/2025] Open
Abstract
Inflammatory myofibroblastic tumor(IMT) is an uncommon soft tissue neoplasm rarely reported in the urinary tract. A 54-year-old male presented to our institution with low back and abdominal pain, hematuria, and lower urinary tract symptoms for 2 months. We performed abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), which showed a mass in the right renal pelvis-inferior calyx. Then, we performed the laparoscopic radical nephroureterectomy.
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Affiliation(s)
- Xiaorui Zhu
- Department of Urology, The Second People's Hospital of Baoshan, No.13 Zhengyang South Road, Longyang District, Baoshan, Yunnan, China
| | - Xueli Dong
- Department of Urology, The Second People's Hospital of Baoshan, No.13 Zhengyang South Road, Longyang District, Baoshan, Yunnan, China
| | - Hongzhou Sheng
- Department of Urology, The Second People's Hospital of Baoshan, No.13 Zhengyang South Road, Longyang District, Baoshan, Yunnan, China
| | - Renbin Deng
- Department of Urology, The Second People's Hospital of Baoshan, No.13 Zhengyang South Road, Longyang District, Baoshan, Yunnan, China
| | - Xianzhong Duan
- Department of Urology, The Second People's Hospital of Baoshan, No.13 Zhengyang South Road, Longyang District, Baoshan, Yunnan, China
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Moodley J, Chebib I. Emerging fusion-associated mesenchymal tumours: a tabular guide and appraisal of five 'novel' entities. J Clin Pathol 2025; 78:145-153. [PMID: 39304199 DOI: 10.1136/jcp-2024-209460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 08/08/2024] [Indexed: 09/22/2024]
Abstract
AIMS The field of molecular pathology has undergone significant advancements in the clinical impact of sarcoma diagnosis, resulting in challenges to nosology of bone and soft tissue tumours. The surge in molecular data has led to the identification of novel fusions and description of new 'entities'. To illustrate this, we have selected five emerging entities with novel fusions: clear cell stromal tumour of the lung with YAP1::TFE3 fusion, GAB1::ABL1 fusion spindle cell neoplasm, NUTM1-rearranged sarcomas, NR1D1-rearranged sarcomas and calcified chondroid mesenchymal neoplasms. METHODS Literature for the relevant case reports and case series of these five entities were reviewed and clinicopathological data was collected. Additionally, this review includes a table format of recently described fusion-associated mesenchymal neoplasms. RESULTS The morphological and immunohistochemical features, along with diagnostic challenges, are discussed for each entity. CONCLUSIONS Here, we have provided a review of selected emerging mesenchymal neoplasms, which of these neoplasms will meet the threshold to be 'new entities' remains to be determined.
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Affiliation(s)
- Jinesa Moodley
- Anatomical Pathology, BC Cancer Agency, Vancouver, British Columbia, Canada
| | - Ivan Chebib
- Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
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Huang YL, Hsu CC, Huang DDR, Yang JCH, Wu SG. Identification of the molecular characterization and tumor microenvironment of thoracic inflammatory myofibroblastic tumors. J Formos Med Assoc 2025:S0929-6646(25)00040-3. [PMID: 39880703 DOI: 10.1016/j.jfma.2025.01.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/20/2025] [Accepted: 01/24/2025] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND Inflammatory myofibroblastic tumors (IMTs), rare soft tissue neoplasms, are characterized by a blend of myofibroblastic proliferation and inflammatory features. While generally characterized by slow growth, IMTs can exhibit locally aggressive behavior, and in rare instances, metastasize to distant sites. This study elucidated the clinical characteristics, molecular profile, and tumor microenvironment of thoracic IMTs. METHODS We retrospectively analyzed cases of IMTs diagnosed at the National Taiwan University Hospital between 2000 and 2020. ALK immunohistochemistry (IHC) was performed, followed by fluorescence in situ hybridization (FISH) for confirmation. Next-generation sequencing (NGS) was employed to detect unknown oncogenic drivers, and multiplex immunofluorescence staining was used to characterize the tumor microenvironment. Demographic, clinicopathological characteristics, and treatment outcomes were systematically recorded and analyzed. RESULTS We identified a total of 8 patients with thoracic IMTs, whose median age of the participants was 33.8 years (range: 18.6-58.7). The disease status of all tumors were early-stage, and all patients underwent surgical excision. ALK fusions were detected in 6 tumors (all spindle-cell patterns), with fusion partners including 3 TPM3, 2 DCTN1, and one EML4. In the remaining 2 tumors without ALK fusion, NGS showed NTRK3 alteration with high gene expressions. Multiplex IHC of three cases identified a pronounced infiltration of macrophages cells within the tumor microenvironment. CONCLUSION Patients with thoracic IMT patients are typically young with early-stage disease. ALK fusion were the most common genetic alteration, particularly in spindle-cell patterns. Characterization of the tumor microenvironment indicates the potential of immune profiling in the tumor biology and targeted immunotherapy approaches.
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Affiliation(s)
- Yen-Lin Huang
- Department of Pathology, National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan
| | - Chia-Chi Hsu
- Graduate Institute of Oncology, Cancer Research Center, National Taiwan University, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Derek De-Rui Huang
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Oncology, National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan
| | - James Chih-Hsin Yang
- Graduate Institute of Oncology, Cancer Research Center, National Taiwan University, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Oncology, National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan
| | - Shang-Gin Wu
- Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
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Cochin T, Noal S, Stefan D, Bodet D, Rouger J, Dorbeau M, Neviere Z. Case report: Musculoskeletal metastastic inflammatory myofibroblastic tumor (IMT) treated by sequential ALK-TKI with longterm response. Front Oncol 2025; 14:1505257. [PMID: 39931211 PMCID: PMC11808025 DOI: 10.3389/fonc.2024.1505257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 12/23/2024] [Indexed: 02/13/2025] Open
Abstract
Inflammatory myofibroblastic tumors (IMTs) are known to be associated with rearrangements of the anaplastic lymphoma kinase (ALK) gene. The treatment of this type of tumor includes systemic therapies such as chemotherapies or anti-inflammatories; in recent years, targeted anti-ALK therapies have emerged and became the standard of care in ALK rearranged patients. We aimed to present a rare case of musculoskeletal IMT with ALK rearrangement, characterized by metastatic evolution and enhanced responses to sequential treatment with all ALK-TKI. We have outlined a potential treatment pathway involving sequential ALK-TKI targeted therapies and successive local interventions to control the cancer.
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Affiliation(s)
- Thomas Cochin
- Department of Radiation Oncology, Centre François Baclesse, Caen, France
| | - Sabine Noal
- Department of Sarcoma Oncology, Centre François Baclesse, Caen, France
| | - Dinu Stefan
- Department of Radiation Oncology, Centre François Baclesse, Caen, France
| | - Damien Bodet
- Department of Pediatry Oncology, Centre Hospitalier Universitaire, Caen, France
| | - Jérémie Rouger
- Department of Pediatry Oncology, Centre Hospitalier Universitaire, Caen, France
| | - Marine Dorbeau
- Department of Pathology, Centre François Baclesse, Caen, France
| | - Zoé Neviere
- Department of Sarcoma Oncology, Centre François Baclesse, Caen, France
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Al-Ibraheemi A, Zhou Y, Rullo E, Alaggio R. What is new in fibroblastic/myofibroblastic tumors in children. Virchows Arch 2025; 486:127-141. [PMID: 39499317 DOI: 10.1007/s00428-024-03964-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 10/23/2024] [Accepted: 10/26/2024] [Indexed: 11/07/2024]
Abstract
Fibroblastic and myofibroblastic neoplasms represent about 12% of pediatric soft tissue tumors. Most of these neoplasms in children are either benign or locally aggressive with rare metastasis, while malignant cases are uncommon. Diagnosing these tumors is challenging due to overlapping morphologies and the limited utility of immunohistochemistry. Advances in molecular techniques, especially RNA sequencing, have improved our understanding of the molecular drivers of these tumors, leading to better classification. Key molecular alterations, such as RTK and MAPK activation, are central in the development of tumors like infantile fibrosarcoma (IFS) and inflammatory myofibroblastic tumors (IMT). The identification of alternative fusions in IFS and IMT underscores the importance of an integrated diagnostic approach. Furthermore, new RTK-driven lesions, now included in the WHO's "NTRK-rearranged mesenchymal neoplasms", have been identified. This review provides an update on recent findings in RTK-driven myofibroblastic tumors and highlights novel entities still in need of classification.
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Affiliation(s)
- Alyaa Al-Ibraheemi
- Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
| | - Yan Zhou
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA
| | - Emma Rullo
- IRCCS Ospedale Pediatrico Bambino Gesù, Pathology Unit (Rome), Piazza Sant'Onofrio 4, 00165, Rome, Italy
| | - Rita Alaggio
- IRCCS Ospedale Pediatrico Bambino Gesù, Pathology Unit (Rome), Piazza Sant'Onofrio 4, 00165, Rome, Italy.
- Department of Medical-Surgical Biotechnological Sciences, Sapienza University of Rome, Polo Pontino, 00185, Rome, Italy.
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Batou Y, Aissaoui TE, Farhaoui AE, Zeryouh B, Lachkar A, Zouaidia F, Abdeljaouad N, Yacoubi H. A rare case of inflammatory myofibroblastic tumour of the thigh : A case report and literature review. Radiol Case Rep 2024; 19:6528-6533. [PMID: 39391027 PMCID: PMC11465054 DOI: 10.1016/j.radcr.2024.09.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 10/12/2024] Open
Abstract
Towards the beginning of the twentieth century, inflammatory myofibroblastic tumors were described as neoplasms characterized by myofibroblastic spindle cells with an infiltrate of inflammatory cells. These rare tumors occur mainly in children and young adults with a preferential pulmonary and abdominal location. They have intermediate biological potency with a tendency to local recurrence and rarely metastasize. We describe the case of an adolescent who presented with an inflammatory myofibroblastic tumor of the thigh, a very rare entity that has only been reported in the literature as case reports, and its clinical, radiological, echographic and MRI appearance. The patient underwent complete surgical resection of the mass with healthy margins and did not receive any additional treatment. No sign of recurrence was detected after 6 months of follow-up.
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Affiliation(s)
- Yassine Batou
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
| | - Taha El Aissaoui
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
| | - Amine El Farhaoui
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
| | - Brahim Zeryouh
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
| | - Adnane Lachkar
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
| | - Fouad Zouaidia
- Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
- Department of Pathological Anatomy, Ibn Sina University Hospital, Mohammed V University Rabat, Morocco
| | - Najib Abdeljaouad
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
| | - Hicham Yacoubi
- Faculty of Medicine and Pharmacy, Mohammed I University, Oujda, Morocco
- Department of Traumatology, orthopedic Mohammed VI University Hospital Mohammed I University, Oujda, Morocco
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Liu M, Zhu D. Two cases of inflammatory myofibroblastic tumor treated with targeted drugs: A case report. Medicine (Baltimore) 2024; 103:e38136. [PMID: 38787978 PMCID: PMC11124583 DOI: 10.1097/md.0000000000038136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/15/2024] [Indexed: 05/26/2024] Open
Abstract
INTRODUCTION Inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue tumor. Many IMTs are positive for anaplastic lymphoma kinase (ALK) with ALK gene fusion; other gene mutations have also been reported, which indicates a key role for genetic testing and the development of target therapy to optimize treatment strategies. PATIENT CONCERNS We report 2 patients who obtained clinical benefits following targeted treatment with ensartinib. DIAGNOSIS The first patient was diagnosed as IMT, with TFG-ROS1 fusion gene mutation. The second patient was IMT harboring the ALK-STRN fusion gene mutation. INTERVENTIONS We performed gene testing for these 2 patients. According to the test result, both patients received ensartinib 225 mg QD as targeted therapy for a 30-day cycle. OUTCOMES The first patient achieved partial remission and maintained a stable state for 14.7 months. The second patient was treated for 10 months and reached complete remission after 5 months and is currently still benefiting from treatment. Treatment-related side effects were mild in both patients. CONCLUSION Our cases provided some new insights and approaches for the clinical diagnosis and treatment of IMT.
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Affiliation(s)
- Mengyao Liu
- Rare Tumors Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Dongyuan Zhu
- Rare Tumors Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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Tong D, Chisholm J, Madden B, Ahmed M. Anaplastic lymphoma kinase-positive pulmonary inflammatory myofibroblastic tumour: a case report. J Med Case Rep 2024; 18:167. [PMID: 38594735 PMCID: PMC11005263 DOI: 10.1186/s13256-024-04472-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 02/23/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Pulmonary inflammatory myofibroblastic tumour (IMT) is a rare condition that usually presents in young individuals and is associated with anaplastic lymphoma kinase (ALK)-translocation. CASE PRESENTATION We report a case of an 18-year-old Caucasian man with ALK-translocated pulmonary IMT treated with multimodality therapy. The patient presented with breathlessness and was found to have a collapsed left lung. Further investigations revealed an ALK-translocated pulmonary IMT. This is usually treated with an ALK-inhibitor but patient declined after discussing potential side-effects and had repeated rigid bronchoscopic interventions for local disease control. Due to persistent local recurrence, patient received radical external beam radiotherapy (EBRT) with pulse steroids, and one year later started on Ibuprofen, a non-steroidal anti-inflammatory agent (NSAID). Following multimodality treatment, he developed a complete response. He remains treatment-free for the past seven years. Eleven years on from his diagnosis, he remains in remission with a ECOG performance status of zero. CONCLUSIONS Achieving long-term local control in pulmonary IMT can be challenging. Multimodality treatment is sometimes needed but the overall outlook remains good.
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Affiliation(s)
- Daniel Tong
- Lung Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
| | - Julia Chisholm
- Children and Young People's Unit, Institute of Cancer Research, Royal Marsden Hospital, Sutton, SM2 5NG, UK
| | - Brendan Madden
- Department of Cardiothoracic Medicine, St Georges Hospital, Blackshaw Road, London, SW17 0QT, UK
| | - Merina Ahmed
- Lung Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK
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Sreepriya PP, Ali MM, Rashi R, Kumar A, Sinha AK, Raj S, Kumar B. Inflammatory Myofibroblastic Tumour in Children: A Report of Two Cases and Review of Literature. Afr J Paediatr Surg 2024; 21:134-137. [PMID: 38546252 PMCID: PMC11003571 DOI: 10.4103/ajps.ajps_106_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 10/03/2022] [Accepted: 10/10/2022] [Indexed: 02/17/2023] Open
Abstract
ABSTRACT Inflammatory myofibroblastic tumour in paediatric patients present with a diagnostic dilemma because of its clinical, radiological and histopathological features overlapping with other mesenchymal tumours common in this age. Because of its rarity, the exact features are still unclear. Here, we are reporting clinical, radiological and histopathological appearances of two such cases. In both cases, the exact diagnosis was confirmed only after immunohistochemistry. There is a need for further detailed study to exactly determine the natural course and prognosis of these tumours.
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Affiliation(s)
- P. P. Sreepriya
- Department of General Surgery, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Md Mokarram Ali
- Department of Paediatric Surgery, Pt B. D. S. PGIMS, Rohtak, Haryana, India
| | - Rashi Rashi
- Department of Paediatric Surgery, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Amit Kumar
- Department of Paediatric Surgery, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Amit Kumar Sinha
- Department of Paediatric Surgery, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Surabhi Raj
- Department of Pathology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Bindey Kumar
- Department of Paediatric Surgery, All India Institute of Medical Sciences, Patna, Bihar, India
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Lim JJ, Chen EY, Schaub SK, Wagner MJ. Reclassification of a spindle cell sarcoma after identification of a TFG-ROS1 fusion: A case demonstrating the clinical benefit of next-generation sequencing in sarcoma. Mol Genet Genomic Med 2024; 12:e2423. [PMID: 38622850 PMCID: PMC11019117 DOI: 10.1002/mgg3.2423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 02/14/2024] [Accepted: 03/19/2024] [Indexed: 04/17/2024] Open
Abstract
BACKGROUND Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal soft tissue sarcomas that often present diagnostic challenges due to their wide and varied morphology. A subset of IMTs have fusions involving ALK or ROS1. The role of next-generation sequencing (NGS) for classification of unselected sarcomas remains controversial. METHODS AND RESULTS We report a case of a metastatic sarcoma in a 34-year-old female originally diagnosed as an unclassified spindle cell sarcoma with myofibroblastic differentiation and later reclassified as IMT after NGS revealed a TFG-ROS1 rearrangement. Histologically, the neoplasm had spindle cell morphology with a lobulated to focally infiltrative growth pattern with scant inflammatory cell infiltrate. Immunohistochemistry demonstrated focal desmin and variable smooth muscle actin staining but was negative for SOX10, S100, and CD34. Fluorescence in situ hybridization was negative for USP6 or ALK gene rearrangements. NGS revealed a TFG-ROS1 rearrangement and the patient was treated with crizotinib with clinical benefit. CONCLUSIONS We discuss the role of NGS as well as its potential benefit in patients with unresectable, ALK-negative metastatic disease. Considering this case and previous literature, we support the use of NGS for patients requiring systemic treatment.
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Affiliation(s)
- John J. Lim
- Division of Medical OncologyUniversity of WashingtonSeattleWashingtonUSA
| | - Eleanor Y. Chen
- Department of Laboratory Medicine and PathologyUniversity of WashingtonSeattleWashingtonUSA
| | | | - Michael J. Wagner
- Division of Medical OncologyUniversity of WashingtonSeattleWashingtonUSA
- Clinical Research DivisionFred Hutchinson Cancer CenterSeattleWashingtonUSA
- Present address:
Center for Sarcoma and Bone OncologyDana Farber Cancer InstituteBostonMassachusettsUSA
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12
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Wachtel M, Surdez D, Grünewald TGP, Schäfer BW. Functional Classification of Fusion Proteins in Sarcoma. Cancers (Basel) 2024; 16:1355. [PMID: 38611033 PMCID: PMC11010897 DOI: 10.3390/cancers16071355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 03/25/2024] [Accepted: 03/27/2024] [Indexed: 04/14/2024] Open
Abstract
Sarcomas comprise a heterogeneous group of malignant tumors of mesenchymal origin. More than 80 entities are associated with different mesenchymal lineages. Sarcomas with fibroblastic, muscle, bone, vascular, adipocytic, and other characteristics are distinguished. Nearly half of all entities contain specific chromosomal translocations that give rise to fusion proteins. These are mostly pathognomonic, and their detection by various molecular techniques supports histopathologic classification. Moreover, the fusion proteins act as oncogenic drivers, and their blockade represents a promising therapeutic approach. This review summarizes the current knowledge on fusion proteins in sarcoma. We categorize the different fusion proteins into functional classes, including kinases, epigenetic regulators, and transcription factors, and describe their mechanisms of action. Interestingly, while fusion proteins acting as transcription factors are found in all mesenchymal lineages, the others have a more restricted pattern. Most kinase-driven sarcomas belong to the fibroblastic/myofibroblastic lineage. Fusion proteins with an epigenetic function are mainly associated with sarcomas of unclear differentiation, suggesting that epigenetic dysregulation leads to a major change in cell identity. Comparison of mechanisms of action reveals recurrent functional modes, including antagonism of Polycomb activity by fusion proteins with epigenetic activity and recruitment of histone acetyltransferases by fusion transcription factors of the myogenic lineage. Finally, based on their biology, we describe potential approaches to block the activity of fusion proteins for therapeutic intervention. Overall, our work highlights differences as well as similarities in the biology of fusion proteins from different sarcomas and provides the basis for a functional classification.
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Affiliation(s)
- Marco Wachtel
- Department of Oncology and Children’s Research Center, University Children’s Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland
| | - Didier Surdez
- Balgrist University Hospital, Faculty of Medicine, University of Zurich (UZH), CH-8008 Zurich, Switzerland
| | - Thomas G. P. Grünewald
- Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
- Hopp-Children’s Cancer Center (KiTZ), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership between DKFZ and Heidelberg University Hospital, 69120 Heidelberg, Germany
- Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Beat W. Schäfer
- Department of Oncology and Children’s Research Center, University Children’s Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland
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Li J, Liu J, Yao X, Yang J. A rare inflammatory myofibroblastic tumor appearing both inside and outside the heart. Eur J Med Res 2024; 29:132. [PMID: 38368344 PMCID: PMC10874007 DOI: 10.1186/s40001-024-01710-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 02/02/2024] [Indexed: 02/19/2024] Open
Abstract
BACKGROUND Inflammatory myofibroblastic tumor (IMT) is an uncommon cardiac tumor that primarily affects infants, children, and young adults. While complete surgical resection generally leads to a favorable prognosis, accurate diagnostic tests remain limited. CASE PRESENTATION We describe the case of a 26-year-old female who had a dual tumor inside and outside the heart and was misdiagnosed by echocardiography and MRI. We also review 71 cases of cardiac IMTs from the literature regarding their epidemiology, clinical presentation, and outcome. CONCLUSION Early detection of this rare disorder is essential for optimal surgical management.
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Affiliation(s)
- Jiarong Li
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China
| | - Jijia Liu
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China
| | - Xingwang Yao
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
| | - Jinfu Yang
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China.
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14
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Sakoda S, Tanaka K, Koga Y, Mikumo H, Tsuchiya‐Kawano Y, Harada E, Tamiya S, Okamoto I. A case of inflammatory myofibroblastic tumor harboring EML4-ALK fusion with a brain metastasis responding to alectinib. Thorac Cancer 2024; 15:415-418. [PMID: 38213097 PMCID: PMC10864117 DOI: 10.1111/1759-7714.15203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/07/2023] [Indexed: 01/13/2024] Open
Abstract
Metastatic inflammatory myofibroblastic tumor (IMT) is very rare and detailed reports on diagnosis and treatment are limited. Here, we report a case of metastatic IMT with ALK rearrangement. A 73-year-old woman was diagnosed with IMT involving a brain metastasis. Next generation sequencing (NGS) panel testing with Oncomine dx target test revealed that her tumor was positive for EML4-ALK. Treatment with alectinib was initiated, resulting in remarkable shrinkage of both the primary tumor and the brain metastasis. This report is the first to identify ALK rearrangement in IMT using a commercially available NGS panel testing, followed by treatment with alectinib. This case suggests that NGS panel testing may be useful in the diagnosis and treatment of patients with metastatic IMT.
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Affiliation(s)
- Soichiro Sakoda
- Department of Respiratory Medicine, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Respiratory MedicineKitakyushu Municipal Medical CenterFukuokaJapan
| | - Kentaro Tanaka
- Department of Respiratory Medicine, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Yuichiro Koga
- Department of Respiratory MedicineKitakyushu Municipal Medical CenterFukuokaJapan
| | - Hironori Mikumo
- Department of Respiratory MedicineKitakyushu Municipal Medical CenterFukuokaJapan
| | - Yuko Tsuchiya‐Kawano
- Department of Respiratory MedicineKitakyushu Municipal Medical CenterFukuokaJapan
| | - Eiji Harada
- Department of Respiratory MedicineKitakyushu Municipal Medical CenterFukuokaJapan
| | - Sadafumi Tamiya
- Department of PathologyKitakyushu Municipal Medical CenterFukuokaJapan
| | - Isamu Okamoto
- Department of Respiratory Medicine, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
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15
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Rerkpichaisuth V, Hung YP. Mesenchymal tumours of the pleura: review and update. Histopathology 2024; 84:163-182. [PMID: 37691389 DOI: 10.1111/his.15035] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 08/10/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023]
Abstract
Primary mesenchymal tumours of the pleura are uncommon and can be diagnostically challenging due to their overlapping histopathologic and immunophenotypic features. Herein we discuss selected mesenchymal tumours of the pleura, including solitary fibrous tumour, calcifying fibrous tumour, desmoid fibromatosis, synovial sarcoma, schwannoma, malignant peripheral nerve sheath tumour, inflammatory myofibroblastic tumour, follicular dendritic cell sarcoma, epithelioid hemangioendothelioma, and desmoplastic small round cell tumour. We review their clinicopathologic characteristics, along with an update on the relevant immunohistochemical and molecular features.
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Affiliation(s)
- Vilasinee Rerkpichaisuth
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Yin P Hung
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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16
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Sommer S, Schmutz M, Schaller T, Mayr P, Dintner S, Märkl B, Huss R, Golas MM, Kuhlen M, Jordan F, Claus R, Heinrich B. Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT). Cancer Rep (Hoboken) 2024; 7:e1916. [PMID: 37950626 PMCID: PMC10809190 DOI: 10.1002/cnr2.1916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/16/2023] [Accepted: 10/08/2023] [Indexed: 11/13/2023] Open
Abstract
BACKGROUND Inflammatory myofibroblastic tumor (IMTs) are rare mesenchymal neoplasms with slow growth. Resection is considered as therapeutic standard, with chemotherapy being insufficiently effective in advanced disease. ALK translocations are present in 50% of cases, ROS1 fusions (YWHAE::ROS1, TFG::ROS1) are extremely rare. Here, we present a case with TFG::ROS1 fusion and highlight the significance of molecular tumor boards (MTBs) in clinical precision oncology for post-last-line therapy. CASE PRESENTATION A 32-year-old woman presented with IMT diagnosed at age 27 for biopsy and treatment evaluation. Previous treatments included multiple resections and systemic therapy with vinblastine, cyclophosphamide, and methotrexate. A computed tomography scan showed extensive tumor infiltration of the psoas muscles and the posterior abdomen. Next generation sequencing revealed an actionable ROS1 fusion (TFG::ROS1) with breakpoints at exon 4/35 including the kinase domain and activating the RAS-pathway. TFG, the Trk-fused gene, exerts functions such as intracellular trafficking and exhibits high sequence homology between species. Based on single reports about efficacy of ROS1-targeting in ROS1 translocation positive IMTs the patient was started on crizotinib, an ATP-competitive small molecule c-MET, ALK and ROS1-inhibitor. With a follow-up of more than 9 months, the patient continues to show a profound response with major tumor regression, improved quality of life and no evidence for severe adverse events. CONCLUSION This case underscores the importance of the availability of modern molecular diagnostics and interdisciplinarity in precision oncology to identify rare, disease-defining genotypes that make an otherwise difficult-to-treat disease targetable.
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Affiliation(s)
- Sebastian Sommer
- Department of Hematology and OncologyFaculty of Medicine, University of AugsburgAugsburgGermany
| | - Maximilian Schmutz
- Department of Hematology and OncologyFaculty of Medicine, University of AugsburgAugsburgGermany
| | - Tina Schaller
- General Pathology and Molecular Diagnostics, Faculty of MedicineUniversity of AugsburgAugsburgGermany
| | - Patrick Mayr
- Department of Hematology and OncologyFaculty of Medicine, University of AugsburgAugsburgGermany
| | - Sebastian Dintner
- General Pathology and Molecular Diagnostics, Faculty of MedicineUniversity of AugsburgAugsburgGermany
| | - Bruno Märkl
- General Pathology and Molecular Diagnostics, Faculty of MedicineUniversity of AugsburgAugsburgGermany
| | - Ralf Huss
- General Pathology and Molecular Diagnostics, Faculty of MedicineUniversity of AugsburgAugsburgGermany
| | - M. Monika Golas
- Department of Hematology and OncologyFaculty of Medicine, University of AugsburgAugsburgGermany
- Human Genetics, Faculty of MedicineUniversity of AugsburgAugsburgGermany
| | - Michaela Kuhlen
- Pediatrics and Adolescent Medicine, Faculty of MedicineUniversity of AugsburgAugsburgGermany
- Swabian Children's Cancer CenterUniversity Medical Center AugsburgAugsburgGermany
| | - Frank Jordan
- Department of Hematology and OncologyFaculty of Medicine, University of AugsburgAugsburgGermany
| | - Rainer Claus
- General Pathology and Molecular Diagnostics, Faculty of MedicineUniversity of AugsburgAugsburgGermany
- Comprehensive Cancer Center Augsburg (CCCA), Faculty of MedicineUniversity of AugsburgAugsburgGermany
| | - Bernhard Heinrich
- Heinrich/BangerterHämatologie‐Onkologie im Zentrum MVZAugsburgGermany
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17
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Wang QA, Chen HW, Wu RC, Wu CE. Update of Diagnosis and Targeted Therapy for ALK + Inflammation Myofibroblastic Tumor. Curr Treat Options Oncol 2023; 24:1683-1702. [PMID: 37938503 PMCID: PMC10781869 DOI: 10.1007/s11864-023-01144-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2023] [Indexed: 11/09/2023]
Abstract
OPINION STATEMENT: Inflammatory myofibroblastic tumor (IMT), characterized by intermediate malignancy and a propensity for recurrence, has presented a formidable clinical challenge in diagnosis and treatment. Its pathological characteristics may resemble other neoplasms or reactive lesions, and the treatment was limited, taking chemotherapies as the only option for those inoperable. However, discovering anaplastic lymphoma kinase (ALK) protein expression in approximately 50% of IMT cases has shed light on a new diagnostic approach and application of targeted therapies. With the previous success of combating ALK+ non-small-cell lung cancers with ALK tyrosine kinase inhibitors (TKIs), crizotinib, a first-generation ALK-TKI, was officially approved by the U.S. Food and Drug Administration in 2020, to treat unresectable ALK+ IMT. After the approval of crizotinib, other ALK-TKIs, such as ceritinib, alectinib, brigatinib, and lorlatinib, have proven their efficacy on ALK+ IMT with sporadic case reports. The sequential treatments of targeted therapies in may provide the insight into the choice of ALK-TKIs in different lines of treatment for unresectable ALK+ IMT.
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Affiliation(s)
- Qi-An Wang
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Huan-Wu Chen
- Division of Emergency and Critical Care Radiology, Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taiwan
| | - Ren-Chin Wu
- Department of Pathology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Chiao-En Wu
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
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18
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Shreenivas A, Janku F, Gouda MA, Chen HZ, George B, Kato S, Kurzrock R. ALK fusions in the pan-cancer setting: another tumor-agnostic target? NPJ Precis Oncol 2023; 7:101. [PMID: 37773318 PMCID: PMC10542332 DOI: 10.1038/s41698-023-00449-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 09/05/2023] [Indexed: 10/01/2023] Open
Abstract
Anaplastic lymphoma kinase (ALK) alterations (activating mutations, amplifications, and fusions/rearrangements) occur in ~3.3% of cancers. ALK fusions/rearrangements are discerned in >50% of inflammatory myofibroblastic tumors (IMTs) and anaplastic large cell lymphomas (ALCLs), but only in ~0.2% of other cancers outside of non-small cell lung cancer (NSCLC), a rate that may be below the viability threshold of even large-scale treatment trials. Five ALK inhibitors -alectinib, brigatinib, ceritinb, crizotinib, and lorlatinib-are FDA approved for ALK-aberrant NSCLCs, and crizotinib is also approved for ALK-aberrant IMTs and ALCL, including in children. Herein, we review the pharmacologic tractability of ALK alterations, focusing beyond NSCLC. Importantly, the hallmark of approved indications is the presence of ALK fusions/rearrangements, and response rates of ~50-85%. Moreover, there are numerous reports of ALK inhibitor activity in multiple solid and hematologic tumors (e.g., histiocytosis, leiomyosarcoma, lymphoma, myeloma, and colorectal, neuroendocrine, ovarian, pancreatic, renal, and thyroid cancer) bearing ALK fusions/rearrangements. Many reports used crizotinib or alectinib, but each of the approved ALK inhibitors have shown activity. ALK inhibitor activity is also seen in neuroblastoma, which bear ALK mutations (rather than fusions/rearrangements), but response rates are lower (~10-20%). Current data suggests that ALK inhibitors have tissue-agnostic activity in neoplasms bearing ALK fusions/rearrangements.
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Affiliation(s)
- Aditya Shreenivas
- Medical College of Wisconsin (MCW) Cancer Center, Milwaukee, WI, USA.
| | | | - Mohamed A Gouda
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hui-Zi Chen
- Medical College of Wisconsin (MCW) Cancer Center, Milwaukee, WI, USA
| | - Ben George
- Medical College of Wisconsin (MCW) Cancer Center, Milwaukee, WI, USA
| | - Shumei Kato
- Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA
| | - Razelle Kurzrock
- Medical College of Wisconsin (MCW) Cancer Center, Milwaukee, WI, USA.
- University of Nebraska, Omaha, NE, USA.
- Worldwide Innovative Network (WIN) for Personalized Cancer Therapy, Chevilly-Larue, France.
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19
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Ohba S, Matsumoto F, Kojima M, Fujimaki M, Fukumura Y, Ikeda K. Inflammatory Myofibroblastic Tumor (IMT) of the Trachea Excised by Transtracheal Surgery: Case Report. EAR, NOSE & THROAT JOURNAL 2023; 102:511-515. [PMID: 34006125 DOI: 10.1177/01455613211014076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
This report describes an extremely rare case of a primary inflammatory myofibroblastic tumor of the trachea. The patient underwent surgical resection by a transtracheal approach and reconstruction with esophageal tracheoplasty. This case report highlights the rarity of such tumors and a minimally invasive and safe surgical technique for tumors around the central neck structures.
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Affiliation(s)
- Shinichi Ohba
- Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Hongo, Bunkyo-ku, Japan
| | - Fumihiko Matsumoto
- Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Hongo, Bunkyo-ku, Japan
| | - Masataka Kojima
- Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Hongo, Bunkyo-ku, Japan
| | - Mitsuhisa Fujimaki
- Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Hongo, Bunkyo-ku, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Hongo, Tokyo, Japan
| | - Katsuhisa Ikeda
- Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Hongo, Bunkyo-ku, Japan
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20
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Cordier F, Hoorens A, Ferdinande L, Van Dorpe J, Creytens D. Inflammatory myofibroblastic tumor of the distal common bile duct: Literature review with focus on pathological examination. World J Clin Cases 2023; 11:4734-4739. [PMID: 37584005 PMCID: PMC10424039 DOI: 10.12998/wjcc.v11.i20.4734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 05/31/2023] [Accepted: 06/26/2023] [Indexed: 07/06/2023] Open
Abstract
Inflammatory myofibroblastic tumor (IMT) of the biliary tract is rare, and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features. Histologically, IMTs are (myo)fibroblastic neoplasms with a prominent inflammatory infiltrate. They are characterized by receptor tyrosine kinase gene rearrangements, most often involving an anaplastic lymphoma kinase (ALK) translocation. The final diagnosis of IMT depends on histopathology and immunohistochemical examination. In this manuscript, we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.
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Affiliation(s)
- Fleur Cordier
- Department of Pathology, Ghent University Hospital, Ghent 9000, Belgium
| | - Anne Hoorens
- Department of Pathology, Ghent University Hospital, Ghent 9000, Belgium
| | | | - Jo Van Dorpe
- Department of Pathology, Ghent University Hospital, Ghent 9000, Belgium
| | - David Creytens
- Department of Pathology, Ghent University Hospital, Ghent 9000, Belgium
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21
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Nayyar V, Bhutia O, Kakkar A, Mishra D. Epithelioid inflammatory myofibroblastic sarcoma arising in the maxilla: first reported case in the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 2023; 136:e15-e19. [PMID: 37246059 DOI: 10.1016/j.oooo.2023.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 02/11/2023] [Accepted: 03/06/2023] [Indexed: 05/30/2023]
Abstract
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare variant of inflammatory myofibroblastic tumors located mostly in the intra-abdominal region. Herein, we present a case of a 32-year-old male with a lobulated growth in the right maxilla. Radiology revealed a solitary osteolytic lesion with an irregular margin, causing buccal and palatal cortex erosion. Histopathology revealed a tumor composed of spindle-shaped fascicles that blend into sheets of round to ovoid-shaped epithelioid cells, areas of myxoid changes, and necrosis. Tumor cells showed a moderate amount of eosinophilic cytoplasm, large vesicular nuclei with coarse chromatin, nuclear pleomorphism, and increased mitoses. Tumor cells were immunopositive for ALK-1, focal positivity for smooth muscle actin, panCK, epithelial membrane antigen, and immunonegativity for CD 30, desmin, CD34, and STAT6. P53 showed a wild-type staining pattern, and INI-1 expression was retained. The Ki-67 proliferative index was 22%. To the best of our knowledge, this is the first case of EIMS occurring in the maxilla.
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Affiliation(s)
- Vivek Nayyar
- Department of Oral Pathology and Microbiology, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Ongkila Bhutia
- Department of Oral and Maxillofacial Surgery, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Aanchal Kakkar
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Deepika Mishra
- Department of Oral Pathology and Microbiology, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India.
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22
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Son SM, Woo CG, Lee OJ, Kim YJ, Lee HC. Inflammatory myofibroblastic tumor of the urinary bladder with FN1‑ALK gene fusion: A case report. Oncol Lett 2023; 25:227. [PMID: 37153035 PMCID: PMC10157617 DOI: 10.3892/ol.2023.13813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 03/29/2023] [Indexed: 05/09/2023] Open
Abstract
Inflammatory myofibroblastic tumors (IMTs), which are rare tumors, exhibit myofibroblastic differentiation, often with anaplastic lymphoma kinase (ALK) gene rearrangements. A subset of IMTs identified in the urinary tract have been shown to harbor a fibronectin 1 (FN1)-ALK gene fusion. In this case report, a case of an IMT with FN1-ALK fusion in the urinary bladder was presented, and its clinicopathological characteristics were reviewed. A 45-year-old female was referred to Chungbuk National University Hospital with gross hematuria. Cystoscopy revealed a solid mass in the bladder. The patient subsequently underwent transurethral resection of the lesion. The mass comprised stellate and spindled myofibroblastic cells that were arranged in loose fascicles, with a myxoid background and a mixed inflammatory infiltrate. Immunohistochemical analysis revealed that the tumor cells were positive for vimentin, cytokeratin AE1/AE3 and ALK, and focal-positive for desmin. Targeted next-generation sequencing was subsequently employed to identify the FN1-ALK fusion. To date, the patient has undergone outpatient follow-up for 18 months, with no signs of tumor recurrence. To conclude, in total, FN1 has been identified as an ALK fusion partner almost exclusively in cases of genitourinary IMTs [13 bladder IMTs (including the present case) and two uterine IMTs]. In the present case, the FN1-ALK fusion was found to involve ALK exon 19 and FN1 exon 23. By contrast, the majority of the other IMTs with an ALK fusion have involved ALK exon 20, whereas ALK fusion involving ALK exon 18 or 19 has been reported only in genitourinary IMTs. Therefore, the FN1-ALK fusion involving ALK exon 18 or 19 may be specific to a subset of IMTs arising in the urinary bladder.
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Affiliation(s)
- Seung-Myoung Son
- Department of Pathology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, North Chungcheong 28644, Republic of Korea
| | - Chang Gok Woo
- Department of Pathology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, North Chungcheong 28644, Republic of Korea
| | - Ok-Jun Lee
- Department of Pathology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, North Chungcheong 28644, Republic of Korea
| | - Yong June Kim
- Department of Urology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, North Chungcheong 28644, Republic of Korea
| | - Ho-Chang Lee
- Department of Pathology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, North Chungcheong 28644, Republic of Korea
- Correspondence to: Dr Ho-Chang Lee, Department of Pathology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, 1 Chungdae-ro, Seowon, Cheongju, North Chungcheong 28644, Republic of Korea, E-mail:
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23
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Devins KM, Samore W, Nielsen GP, Deshpande V, Oliva E. Leiomyoma-like Morphology in Metastatic Uterine Inflammatory Myofibroblastic Tumors. Mod Pathol 2023; 36:100143. [PMID: 36806735 DOI: 10.1016/j.modpat.2023.100143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 02/06/2023] [Accepted: 02/10/2023] [Indexed: 02/19/2023]
Abstract
Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that frequently harbor ALK gene rearrangements and have a low risk of metastasis. We reported 3 of these tumors mimicking the appearance of leiomyoma in their recurrence. These patients were 34, 43, and 45 years old. Two uterine tumors demonstrated classic morphology, with combined myxoid, compact fascicular, and hyalinized patterns and spindled cells with bipolar cytoplasmic processes, moderate atypia, and lymphoplasmacytic inflammatory infiltrates. The third had a "leiomyoma-like" appearance, with fascicles of plump spindled cells and a sparse lymphoplasmacytic infiltrate. ALK immunohistochemistry was positive in all the tumors, and all demonstrated ALK rearrangements using fluorescence in situ hybridization (n = 2) and/or RNA sequencing (n = 2). Two classic IMTs recurred at 3 and 50 months in the lung and abdomen, respectively, and recurrent tumors had a "leiomyoma-like" appearance, with 0 and 1 mitosis per 10 high-power fields, no inflammation in 1, and a sparse lymphocytic infiltrate in the other. ALK was positive in both tumors; 1 with available tissue showed an IGFBP5::ALK fusion using RNA sequencing. The third patient, who had a "leiomyoma-like" uterine tumor, experienced multiple recurrences, first in the abdomen at 100 months showing a similar appearance. Subsequent recurrence at 105 months showed transmural invasion of the sigmoid colon and a similar microscopic appearance but with the addition of infiltrative borders, moderate cellularity, mild-to-moderate atypia, and 10 mitoses per 10 high-power fields. Both recurrences were positive for ALK, and RNA sequencing revealed the same ACTG2::ALK fusion transcript identified in the primary tumor. The patient was treated with crizotinib, resulting in prolonged clinical remission, with no evidence of disease at 168 months from the initial surgery. Although "leiomyoma-like" uterine IMTs have been recently described, to our knowledge, this is the first report of recurrence of these tumors and the first report of a "leiomyoma-like" appearance in the recurrences of conventional uterine IMTs. A low threshold for performing ALK immunohistochemistry on recurrent uterine tumors can identify patients who may benefit from tyrosine kinase inhibitors.
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Affiliation(s)
- Kyle M Devins
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Wesley Samore
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - G Petur Nielsen
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Vikram Deshpande
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Esther Oliva
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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24
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Zhang Y, Liu J. Inflammatory myofibroblastic tumor of the thyroid gland. Front Endocrinol (Lausanne) 2023; 14:1156117. [PMID: 37255972 PMCID: PMC10225677 DOI: 10.3389/fendo.2023.1156117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 05/01/2023] [Indexed: 06/01/2023] Open
Abstract
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor with low incidence, which is extremely rare in the thyroid. At present, there is a lack of understanding regarding the etiology, pathogenesis, diagnosis and treatment of thyroid IMT. To improve the understanding of the disease, this article reviews the pathogenesis, clinical manifestations, pathology and immunohistochemistry, diagnosis, therapy and prognosis of thyroid IMT.
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25
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Prijovic N, Santric V, Babic U, Stankovic B, Acimovic M, Cekerevac M, Nikolic G, Cegar B. Inflammatory Myofibroblastic Tumour of the Urinary Bladder in a Middle-Aged Man-A Case Report of an Unusual Localization of a Rare Tumour. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59040791. [PMID: 37109749 PMCID: PMC10144372 DOI: 10.3390/medicina59040791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/04/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023]
Abstract
Inflammatory myofibroblastic tumour (IMT) is a rare tumour with an intermediate biological behaviour. It usually occurs in children and adolescents, primarily in the abdomen or lungs. Histopathologically, IMT consists of spindle cells, i.e., myofibroblasts, and a variable inflammatory component. Localization in the urinary bladder is rare. We are presenting a rare case of IMT in the bladder in a middle-aged man treated by partial cystectomy. A 62-year-old man consulted a urologist because of haematuria and dysuric disturbances. A tumorous mass was detected by an ultrasound in the urinary bladder. CT urography described the tumorous mass at the dome of the urinary bladder measuring 2 × 5 cm. A smooth tumorous mass was cystoscopically observed at the dome of the urinary bladder. Transurethral resection of the bladder tumour was performed. Histopathological analysis of the specimen identified spindle cells with a mixed inflammatory infiltrate; immunohistochemical findings showed positivity for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA) and vimentin. A histopathological diagnosis of IMT was established. It was decided that the patient would undergo a partial cystectomy. A complete excision of the tumour from the dome of the urinary bladder with surrounding healthy tissue was performed. Histopathological and immunohistochemical findings of the sample confirmed the diagnosis of IMT, without the presence of the tumour at the surgical margins. The postoperative course went smoothly. IMT is a rare tumour in adults, especially localised in the urinary bladder. IMT of the urinary bladder is difficult to distinguish from urinary bladder malignancy both clinically and radiologically, as well as histopathologically. If the location and size of the tumour allow it, bladder-preserving surgeries such as partial cystectomy represent a reasonable modality of operative treatment.
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Affiliation(s)
- Nebojsa Prijovic
- Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Veljko Santric
- Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Uros Babic
- Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Branko Stankovic
- Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Miodrag Acimovic
- Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Milica Cekerevac
- Department of Pathology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Gorana Nikolic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Bojan Cegar
- Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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Velez Torres JM, Mata DA, Briski LM, Green DC, Cloutier JM, Kerr DA, Montgomery EA, Rosenberg AE. Sinonasal Myxoma: A Distinct Entity or a Myxoid Variant of Desmoid Fibromatosis? Mod Pathol 2023; 36:100189. [PMID: 37059229 DOI: 10.1016/j.modpat.2023.100189] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/23/2023] [Accepted: 04/05/2023] [Indexed: 04/16/2023]
Abstract
Sinonasal myxoma (SNM) is a rare benign mesenchymal tumor that arises in the sinonasal cavity or maxilla and almost exclusively affects young children. Currently, it is considered a specific entity, but its molecular characteristics have not been reported. Lesions diagnosed as SNM and odontogenic myxoma/fibromyxoma (OM/OFM) were identified from the participating institutions, and the clinicopathologic features were recorded. Immunohistochemistry for β-catenin was performed on all cases with available tissue. Next-generation sequencing (NGS) was performed on all SNM cases. Five patients with SNM were identified, including 3 boys and 2 girls with an age range of 20-36 months (mean: 26 months). The tumors were well-defined, centered in the maxillary sinus, surrounded by a rim of woven bone, and composed of a moderately cellular proliferation of spindle cells oriented in intersecting fascicles in a variably myxocollagenous stroma that contained extravasated erythrocytes. Histologically, the tumors resembled myxoid desmoid fibromatosis. Three tested cases showed nuclear expression of β-catenin. In 3 tumors, NGS revealed intragenic deletions of APC exons 5-6, 9 and 15, or 16, respectively, with concurrent loss of the other wild-type copy of APC, predicted to result in biallelic inactivation. The deletions were identical to those that occur in desmoid fibromatosis, and copy-number analysis raised the possibility that they were germline. In addition, one case showed possible deletion of APC exons 12-14, and another case exhibited a CTNNB1 p.S33C mutation. Ten patients with OM/OFM were identified, including 4 women and 6 men (mean age: 42 years). Seven tumors involved the mandible, and 3 the maxilla. Histologically, the tumors differed from SNM, and all cases lacked nuclear expression of β-catenin. These findings suggest that SNM represents a myxoid variant of desmoid fibromatosis that often arises in the maxilla. Because the APC alterations might be germline, genetic testing of the affected patients should be considered.
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Affiliation(s)
- Jaylou M Velez Torres
- Department of Pathology and Laboratory Medicine, University of Miami Hospital, and University of Miami Miller School of Medicine, Miami, FL, USA.
| | | | - Laurence M Briski
- Department of Pathology and Laboratory Medicine, University of Miami Hospital, and University of Miami Miller School of Medicine, Miami, FL, USA
| | - Donald C Green
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, and Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Jeffrey M Cloutier
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, and Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Darcy A Kerr
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, and Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Elizabeth A Montgomery
- Department of Pathology and Laboratory Medicine, University of Miami Hospital, and University of Miami Miller School of Medicine, Miami, FL, USA
| | - Andrew E Rosenberg
- Department of Pathology and Laboratory Medicine, University of Miami Hospital, and University of Miami Miller School of Medicine, Miami, FL, USA
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Han Q, Zhang Z, He X, Chen M, Pang X, Chen C, Du T, Zhang H. Primary inflammatory myofibroblastic tumour of the liver: a clinicopathological and genetic study including a subset with ETV6::NTRK3 fusion. Histopathology 2023; 82:925-936. [PMID: 36748182 DOI: 10.1111/his.14881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 01/31/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023]
Abstract
AIMS Inflammatory myofibroblastic tumour (IMT) is an intermediate neoplasm and rarely occurs in the liver. The aim of this study was to analyse the clinicopathological and genetic features of the largest primary hepatic IMT. METHODS AND RESULTS A total of 10 cases were identified (four males and six females aged 1-48 years, median = 35 years) from 2011 to 2021, which accounted for 2.5% of IMTs occurring in all organ systems. Histological findings revealed that myofibroblastic/fibroblastic cells with inflammatory infiltration and focal hypocellularity were observed in three children. Immunostaining showed ALK-diffuse cytoplasmic positive in six cases (six of 10; 60%) and pan-TRK nuclear positive in three cases (three of 10; 30%). Hypercellular pattern was detected in ALK-positive IMTs and obvious collagenous/myxoid matrix was observed in the pan-TRK-positive subgroup. ALK rearrangement was demonstrated in three of five interpretable ALK-positive IMTs by fluorescence in-situ hybridisation (FISH), and one case failed due to poor sample quality. Next-generation sequencing indicated an IMT with TFG::ALK and FCHSD2::ALK fusion and TP53 mutation. ETV6::NTRK3 fusion was confirmed by RT-PCR, but FISH-negative results were found in two of three cases with pan-TRK-positive IMTs. No genetic alteration was detected in one tumour. One patient died 1 year after biopsy, while nine patients survived without evidence of disease in the follow-up surveillance (17-119 months). CONCLUSIONS This article describes the first example of primary paediatric hepatic IMTs with ETV6::NTRK3 fusion. Besides the common ALK-positive subgroup, the proportion of NTRK3 fusion is high. Recognising the association between clinicopathological and molecular alterations is critical to accurate diagnosis of hepatic IMTs.
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Affiliation(s)
- Qianqian Han
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhang Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xin He
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Min Chen
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaojun Pang
- Department of Pathology, Mian yang Hospital of Traditional Chinese Medicine, Mian yang, Sichuan, China
| | - Chen Chen
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tianhai Du
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hongying Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Moyers JT, Pestana RC, Roszik J, Hong DS, Naing A, Fu S, Piha-Paul S, Yap TA, Karp D, Rodon J, Livingston A, Zarzour MA, Ravi V, Patel S, Benjamin RS, Ludwig J, Herzog C, Ratan R, Somaiah N, Conley A, Gorlick R, Meric-Bernstam F, Subbiah V. Examining Stripes on a Herd of Zebras: Impact of Genomic Matching for Ultrarare Sarcomas in Phase 1 Clinical Trials (SAMBA 102). Clin Cancer Res 2023; 29:401-409. [PMID: 36288393 PMCID: PMC9843435 DOI: 10.1158/1078-0432.ccr-22-2509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/04/2022] [Accepted: 10/24/2022] [Indexed: 01/21/2023]
Abstract
PURPOSE Recently, the Connective Tissue Oncology Society published consensus guidelines for recognizing ultrarare sarcomas (URS), defined as sarcomas with an incidence ≤1 per 1,000,000. We assessed the outcomes of 56 patients with soft tissue, and 21 with bone sarcomas, enrolled in Phase 1 trials. EXPERIMENTAL DESIGN In this Sarcoma-Matched Biomarker Analysis (SAMBA-102 study), we reviewed records from patients on Phase 1 trials at the University of Texas MD Anderson Cancer Center between January 2013 and June 2021. RESULTS Among 587 sarcomas, 106 (18.1%) were classified as URS. Fifty (47%) were male, and the median age was 44.3 years (range, 19-82). The most common subtypes were alveolar soft part sarcoma (ASPS), chordoma, dedifferentiated chondrosarcoma, and sclerosing epithelioid fibrosarcoma. Compared with common sarcomas, median OS was similar 16.1 months [95% confidence interval (CI), 13.6-17.5] versus 16.1 (95% CI, 8.2-24.0) in URS (P = 0.359). Objective response to treatment was higher in URS 13.2% (n = 14/106) compared with common sarcomas 6.9% (n = 33/481; P = 0.029). Median OS for those treated on matched trials was 27.3 months (95% CI, 1.9-52.7) compared with 13.4 months (95% CI, 6.3-20.6) for those not treated on matched trials (P = 0.291). Eight of 33 (24%) molecularly matched treatments resulted in an objective response, whereas 6 of 73 unmatched treatments (8.2%) resulted in an objective response (P = 0.024). Clinical benefit rate was 36.4% (12/33) in matched trials versus 26.0% (19/73) in unmatched trials (P = 0.279). CONCLUSIONS The results demonstrate the benefit of genomic selection in Phase 1 trials to help identify molecular subsets likely to benefit from targeted therapy.
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Affiliation(s)
- Justin T. Moyers
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.,Division of Hematology and Oncology, Department of Medicine, University of California, Irvine, Orange, California
| | - Roberto Carmagnani Pestana
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.,Centro de Oncologia e Hematologia Einstein Familia Dayan-Daycoval, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Jason Roszik
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - David S. Hong
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Aung Naing
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Siqing Fu
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sarina Piha-Paul
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Timothy A. Yap
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Daniel Karp
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jordi Rodon
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Andy Livingston
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Maria Alejandra Zarzour
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Vinod Ravi
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Shreyaskumar Patel
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Robert S. Benjamin
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Joseph Ludwig
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Cynthia Herzog
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ravin Ratan
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Neeta Somaiah
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Anthony Conley
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Richard Gorlick
- Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Funda Meric-Bernstam
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Vivek Subbiah
- Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.,Corresponding Author: Vivek Subbiah, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 455, PO Box 301402, Houston, TX 77030. E-mail:
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29
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Rodrigues HC, Videira W, Rodrigues L, Pinheiro R, Ferro F. Inflammatory myofibroblastic tumor of the lung - an explosive metastatic case. J Bras Pneumol 2022; 48:e20220127. [PMID: 36629632 PMCID: PMC9747178 DOI: 10.36416/1806-3756/e20220127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Affiliation(s)
| | - Wanda Videira
- . Serviço de Pneumologia, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Luís Rodrigues
- . Serviço de Pneumologia, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Rita Pinheiro
- . Serviço de Pneumologia, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Filipa Ferro
- . Serviço de Pneumologia, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
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30
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Tang F, Dai G, Huang X, Wang D. Uterine inflammatory myofibroblastic tumor presented as abnormal uterine bleeding: Two cases report and literature review. Medicine (Baltimore) 2022; 101:e32141. [PMID: 36550868 PMCID: PMC9771253 DOI: 10.1097/md.0000000000032141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
RATIONALE Inflammatory myofibroblastic tumor (IMT) is an extremely rare soft tissue neoplasm consisting of the proliferation of fibroblastic-myofibroblastic cells with inflammatory infiltrates. It is known to occur in many parts of the body and can generally present with benign or locally recurrent behavior. Anaplastic lymphoma kinase is a specific diagnostic marker for IMT, and approximately 50% of IMT patients have anaplastic lymphoma kinase gene rearrangements. Reports of the female genital tract are rare. PATIENT CONCERNS Two patients (a 32-year-old multigravida and a 22-year-old nullipara) visited our clinic because of abnormal uterine bleeding and a uterine mass. DIAGNOSES Histopathological examination, immunohistochemical markers, and fluorescence in situ hybridization confirmed the presence of a rare uterine IMT. INTERVENTIONS The masses were completely resected via hysteroscopy. The multigravida recurred rapidly in terms of symptoms and images, whereas the nullipara was complaint-free during the follow-up period. Finally, the multigravida underwent hysterectomy and bilateral salpingectomies. OUTCOMES AND LESSONS Uterine IMTs can be easily overlooked because of their extremely low incidence rate and insufficient awareness among clinicians; however, uterine IMTs need to be considered in the differential diagnosis of uterine masses. Possible differences in the biological behavior of IMT may exist in different individuals.
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Affiliation(s)
- Furong Tang
- Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Guanlin Dai
- Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Xing Huang
- Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Danqing Wang
- Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
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31
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Nesteryuk V, Hamdani O, Gong R, Almog N, Alexander BM, Soosman S, Yoneda K, Ali SM, Borowsky AD, Riess JW. A Common Cell of Origin for Inflammatory Myofibroblastic Tumor and Lung Adenocarcinoma with ALK rearrangement. Clin Lung Cancer 2022; 23:e550-e555. [PMID: 36253270 DOI: 10.1016/j.cllc.2022.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 08/26/2022] [Accepted: 09/01/2022] [Indexed: 01/27/2023]
Abstract
This case signifies the importance of obtaining tumor comprehensive genomic profiling (CGP) as it has utility in cancer type classification and helping in diagnosing recurrence/metastasis or separately occurring primary tumors. CGP can also help guiding treatment as in this case separately occurring Inflammatory Myofibroblastic Tumor had ALK fusion and responded to crizotinib. As treatment progresses, new biopsies should be obtained and CGP used to evaluate for appearance of any new genomic alterations, in order to guide further therapy.
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Affiliation(s)
- Vasyl Nesteryuk
- Department of Medicine.Division of Hematology/Oncology, UC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Davis, CA
| | - Omar Hamdani
- Clinical Genomics Scientist, Clinical Development and Medical Affairs, Foundation Medicine, Inc., Cambridge, MA
| | - Raymond Gong
- Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Davis, CA
| | - Nava Almog
- Clinical Genomics Scientist, Clinical Development and Medical Affairs, Foundation Medicine, Inc., Cambridge, MA
| | - Brian M Alexander
- Clinical Genomics Scientist, Clinical Development and Medical Affairs, Foundation Medicine, Inc., Cambridge, MA
| | | | - Ken Yoneda
- Department of Medicine. Division of Pulmonary and Critical Care Medicine,UC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Davis, CA
| | - Siraj M Ali
- Clinical Genomics Scientist, Clinical Development and Medical Affairs, Foundation Medicine, Inc., Cambridge, MA
| | - Alexander D Borowsky
- Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Davis, CA
| | - Jonathan W Riess
- Department of Medicine.Division of Hematology/Oncology, UC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Davis, CA.
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32
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Mhashal S, Dokania V, Bhargava S, Gite V, Mayashankar V, Shetty N, Haneef M. S-100 Immuno-Positive Low Grade Myofibroblastic Sarcoma of Nasal Cavity: A Rare Case Presentation and Review of Literature. Indian J Otolaryngol Head Neck Surg 2022; 74:1388-1395. [PMID: 36452705 PMCID: PMC9701993 DOI: 10.1007/s12070-021-02522-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 03/22/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction Myofibroblastic neoplasms comprise a spectrum of benign/malignant neoplasms. Only low-grade malignant forms have been reproducibly characterized as a diagnostic entity in the WHO classification. Low grade myofibroblastic sarcoma (LGMFS) confined to the nasal cavity is extremely rare. Objective To review previously reported cases of nasal cavity LGMFS and provide a better insight regarding its clinical and immunohistochemical features. Data synthesis A review was performed involving two databases (PubMed and Google Scholar). Four cases of nasal cavity LGMFS were included. The lesion showed no gender or nasal-side predilection. All cases underwent wide excision. None showed distant metastasis while half recurred locally. Histologically, mitotic rate ranged from 1 to 3/10 high-power-field (HPF) and none exhibited spontaneous necrosis. Immuno-expression of calponin, smooth muscle actin (SMA) and vimentin were seen in either all four or three-fourth of cases. Diffuse S-100 expression was a unique finding in present case and not reported previously, that caused a diagnostic dilemma with schwannomas. Conclusion LGMFS of nasal cavity is extremely rare. A wide resection is the primary treatment of choice. Adjuvant therapies (chemotherapy or radiotherapy) are of uncertain significance. Distant metastasis is rather unusual. Calponin, SMA and vimentin are highly sensitive immuno-markers. Diffuse S-100 expression is a possible finding. Mitotic rate < 6/10 HPF and absence of spontaneous necrosis are characteristic indolent features differentiating from high grade lesions. Trifecta of clinical and morphological features plus immunohistological phenotype, are sufficient for a definitive diagnosis. Electron microscopy is the most definitive confirmation test, however, should be reserved only for equivocal/atypical immunostaining pattern.
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Affiliation(s)
- Shashikant Mhashal
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
| | - Vivek Dokania
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
| | - Samir Bhargava
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
| | - Vinod Gite
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
| | - Vishwakarma Mayashankar
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
| | - Neeraj Shetty
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
| | - Muhammed Haneef
- Department of Otolaryngology-Head & Neck Surgery, HBT Medical College and Dr RN Cooper Municipal General Hospital, Juhu, Mumbai, Maharashtra India 400056
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Buksh O, Almalki AM, Khogeer A, Al-Maghrabi J, Alakraa M. A Large Inflammatory Myofibroblastic Tumor of the Urinary Bladder in a Parturient Treated by Partial Cystectomy: Case Report and Literature Review. Cureus 2022; 14:e29556. [PMID: 36312673 PMCID: PMC9595141 DOI: 10.7759/cureus.29556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/25/2022] [Indexed: 11/06/2022] Open
Abstract
Inflammatory myofibroblastic tumor (IMT) is a rare type of tumor composed mainly of fibroblastic and myofibroblastic spindle cells, with an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils. IMT may arise from different organs and sites, but it is infrequent to arise from the urinary bladder and usually manifests as hematuria. We report a case of a 24-year-old pregnant woman who presented to our hospital with gross hematuria. After further workup, we concluded that she had this extremely rare tumor, which was resected eventually with a partial cystectomy. Although the diagnosis of these kinds of tumors is usually made by anaplastic lymphoma kinase (ALK) using immunohistochemistry and detecting ALK gene translocation using fluorescence in situ hybridization (FISH), they were negative in our study; hence, we relied mainly on the morphological features of the tumor for the diagnosis.
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34
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Mesenteric inflammatory myofibroblastic tumor mimicking acute appendicitis: A case report. Ann Med Surg (Lond) 2022; 81:104456. [PMID: 36147115 PMCID: PMC9486733 DOI: 10.1016/j.amsu.2022.104456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/13/2022] [Accepted: 08/13/2022] [Indexed: 11/24/2022] Open
Abstract
Introduction An Inflammatory myofibroblastic tumor, a neoplasm of intermediate biological potential, of the small bowel mesentery, is a rare tumor, most commonly reported in but not confined to the pediatric age group. Case presentation This case report underlines a case of a (small bowel) mesentery IMT in an adult female presenting with recurrent symptoms similar to acute appendicitis. Discussion It can present with symptoms similar to acute appendicitis necessitating a high index of suspicion for its prompt diagnosis. Treatment primarily includes surgical resection with recent advances in targeted therapy with tyrosine kinase inhibitors showing promising results. Conclusion IMTs can present as clinical as well as histopathological mimickers of a variety of diseases especially in the abdomen. Prompt diagnosis requires both imaging and histopathological examination.
Inflammatory myofibroblastic tumor is a neoplasm of intermediate biological potential of the small bowel mesentery. Prompt diagnosis requires both imaging and histopathological examination. Surgery still remains the main modality of treatment.
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Huang Y, Shu SN, Zhou H, Liu LL, Fang F. Infant biliary cirrhosis secondary to a biliary inflammatory myofibroblastic tumor: A case report and review of literature. World J Clin Cases 2022; 10:8375-8383. [PMID: 36159551 PMCID: PMC9403675 DOI: 10.12998/wjcc.v10.i23.8375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 06/25/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A biliary inflammatory myofibroblastic tumor (IMT) is a rare type of mesenchymoma that, although it has a broad age spectrum, usually occurs in adults. Diagnosis is difficult because biliary IMTs often exhibit nonspecific clinical symptoms and imaging features, resulting in delayed or inappropriate treatment. Although most IMTs are benign, some show malignant properties such as infiltration, recurrence, and metastasis.
CASE SUMMARY Here, we retrospectively describe a 10-month-old infant who was admitted to our hospital due to stubborn jaundice. The patient responded poorly to routine medical treatment and his clinical manifestations and laboratory tests lacked specificity, so we turned to repeated ultrasound scans and other imaging examinations. As both hepatosplenic ultrasonography and diffusion-weighted magnetic resonance imaging demonstrated a space-occupying lesion, an exploratory laparotomy was performed. The final diagnosis made over two mo after the disease onset was infant biliary cirrhosis caused by a biliary IMT, which partially infiltrated into the liver. This infant is the youngest case of biliary IMTs that has been reported till now. The patient underwent an incomplete resection of the mass and Kasai Portoenterostomy. However, because of cirrhosis, he also received a paternal liver transplant. Since some IMTs show malignant properties, we proceeded with a three-year of follow-up; however, no recurrence or metastasis has been noted.
CONCLUSION Neoplastic disease such as IMTs should be considered when routine medical treatment of obstructive jaundice is not successful. Observation of dynamic imaging changes is helpful for diagnosis. Periodic follow-up is necessary for IMTs.
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Affiliation(s)
- Yuan Huang
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Sai-Nan Shu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Hua Zhou
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ling-Ling Liu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Feng Fang
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Durham C, Clemons M, Alias A, Konduri K. Locally Advanced Inflammatory Myofibroblastic Tumor Treated With Targeted Therapy: A Case Report and Literature Review. Cureus 2022; 14:e27223. [PMID: 36035049 PMCID: PMC9400374 DOI: 10.7759/cureus.27223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2022] [Indexed: 11/30/2022] Open
Abstract
Inflammatory myofibroblastic tumors (IMTs) are known to be associated with anaplastic lymphoma kinase (ALK) gene rearrangements. Other molecular alterations such as ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), neurotrophic tyrosine receptor kinase (NTRK), and platelet-derived growth factor receptor (PDGFR) have also been identified in IMTs. Although there are no randomized controlled clinical trials comparing chemotherapy, tyrosine kinase inhibitors (TKIs), or other systemic therapies, the literature demonstrates the use of ALK-targeted TKIs as an effective strategy for the treatment of locally advanced or metastatic ALK-rearranged IMTs. This case report describes a patient with an ALK-rearranged locally advanced pulmonary IMT who was treated with neoadjuvant-intent crizotinib. The patient had a very favorable response to therapy, and surgery was declined. It is difficult to determine the duration and sequencing of TKI use in these settings as there is little published data to guide decisions. This report also includes a comprehensive compilation of published IMT cases with molecular alterations treated with systemic therapy, which also highlighted the duration of therapies and clinical outcomes.
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Wang X, Hu Y, Zou X, Wang P, Yue H, Guo M, Li Z, Gong P. Discovery of 2,4-diarylaminopyrimidine derivatives bearing dithiocarbamate moiety as novel ALK inhibitors. Bioorg Med Chem 2022; 66:116794. [PMID: 35576654 DOI: 10.1016/j.bmc.2022.116794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/26/2022] [Accepted: 04/30/2022] [Indexed: 11/29/2022]
Abstract
To overcome drug resistance caused by ALK kinase mutations especially G1202R, two series of novel 2,4-diarylaminopyrimidine derivatives bearing dithiocarbamate moiety were designed, synthesized and evaluated for their biological activities. Among all the target compounds, B10 efficiently inhibited the proliferation of ALK-positive Karpas299 and H2228 cells both with IC50 values of 0.07 μM. In addition, B10 exhibited remarkable enzymatic inhibitory potency with IC50 values of 4.59 nM, 2.07 nM and 5.95 nM toward ALKWT, ALKL1196M and ALKG1202R, respectively. Furthermore, B10 induced apoptosis in H2228 cell and caused cell cycle arrest in G2/M phase. Ultimately, the binding modes of B10 with ALKWT and ALKG1202R were ideally established, which further confirmed the structural basis in accordance with the SARs analysis. These results indicated that B10 was a potent ALK inhibitor for ALKG1202R mutation treatment and deserved for further investigation.
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Affiliation(s)
- Xinyue Wang
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Yiran Hu
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Xinyu Zou
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Pengfei Wang
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Hao Yue
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Mingzhang Guo
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Zefei Li
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Ping Gong
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
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Berlak M, Tucker E, Dorel M, Winkler A, McGearey A, Rodriguez-Fos E, da Costa BM, Barker K, Fyle E, Calton E, Eising S, Ober K, Hughes D, Koutroumanidou E, Carter P, Stankunaite R, Proszek P, Jain N, Rosswog C, Dorado-Garcia H, Molenaar JJ, Hubank M, Barone G, Anderson J, Lang P, Deubzer HE, Künkele A, Fischer M, Eggert A, Kloft C, Henssen AG, Boettcher M, Hertwig F, Blüthgen N, Chesler L, Schulte JH. Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells. Mol Cancer 2022; 21:126. [PMID: 35689207 PMCID: PMC9185889 DOI: 10.1186/s12943-022-01583-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 04/22/2022] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated anaplastic lymphoma kinase (ALK) inhibitor resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations. METHODS Genome-wide forward genetic CRISPR-Cas9 based screens were performed to identify genes associated with ALK inhibitor resistance in neuroblastoma cell lines. Furthermore, the neuroblastoma cell line NBLW-R was rendered resistant by continuous exposure to ALK inhibitors. Genes identified to be associated with ALK inhibitor resistance were further investigated by generating suitable cell line models. In addition, tumor and liquid biopsy samples of four patients with ALK-mutated neuroblastomas before ALK inhibitor treatment and during tumor progression under treatment were genomically profiled. RESULTS Both genome-wide CRISPR-Cas9-based screens and preclinical spontaneous ALKi resistance models identified NF1 loss and activating NRASQ61K mutations to confer resistance to chemically diverse ALKi. Moreover, human neuroblastomas recurrently developed de novo loss of NF1 and activating RAS mutations after ALKi treatment, leading to therapy resistance. Pathway-specific perturbations confirmed that NF1 loss and activating RAS mutations lead to RAS-MAPK signaling even in the presence of ALKi. Intriguingly, NF1 loss rendered neuroblastoma cells hypersensitive to MEK inhibition. CONCLUSIONS Our results provide a clinically relevant mechanistic model of ALKi resistance in neuroblastoma and highlight new clinically actionable collateral sensitivities in resistant cells.
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Affiliation(s)
- Mareike Berlak
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- Berlin School of Integrative Oncology (BSIO), Augustenburger Platz 1, 13353, Berlin, Germany
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Kelchstr.31, 12169, Berlin, Germany
| | - Elizabeth Tucker
- Paediatric Solid Tumour Biology and Therapeutics Team, Clinical Division and Cancer Therapeutics Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
| | - Mathurin Dorel
- Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Max Planck Institute for Molecular Genetics, Berlin, Germany
- Institute of Pathology, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany
- IRI Life Sciences, Humboldt University Berlin, 10115, Berlin, Germany
| | - Annika Winkler
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Aleixandria McGearey
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Elias Rodriguez-Fos
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- Experimental and Clinical Research Center (ECRC) of the Charité and Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125, Berlin, Germany
| | - Barbara Martins da Costa
- Paediatric Solid Tumour Biology and Therapeutics Team, Clinical Division and Cancer Therapeutics Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
| | - Karen Barker
- Paediatric Solid Tumour Biology and Therapeutics Team, Clinical Division and Cancer Therapeutics Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
| | - Elicia Fyle
- Paediatric Solid Tumour Biology and Therapeutics Team, Clinical Division and Cancer Therapeutics Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
| | - Elizabeth Calton
- Paediatric Solid Tumour Biology and Therapeutics Team, Clinical Division and Cancer Therapeutics Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
| | - Selma Eising
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Kim Ober
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Deborah Hughes
- Molecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK
| | - Eleni Koutroumanidou
- Molecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK
| | - Paul Carter
- Molecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK
| | - Reda Stankunaite
- Molecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK
| | - Paula Proszek
- Molecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK
| | - Neha Jain
- Cancer Section, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Carolina Rosswog
- Department of Experimental Pediatric Oncology, Center for Molecular Medicine Cologne, 50931, Cologne, Germany
| | - Heathcliff Dorado-Garcia
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Jan Jasper Molenaar
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of pharmaceutical sciences, Utrecht University, Utrecht, The Netherlands
| | - Mike Hubank
- Molecular Diagnostics Department, The Institute of Cancer Research and Clinical Genomics, The Royal Marsden NHS Foundation, London, UK
| | - Giuseppe Barone
- Cancer Section, UCL Great Ormond Street Institute of Child Health, London, UK
| | - John Anderson
- Cancer Section, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Peter Lang
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- Department of Pediatric Hematology and Oncology, University Hospital, Tübingen, Germany
| | - Hedwig Elisabeth Deubzer
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- Experimental and Clinical Research Center (ECRC) of the Charité and Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125, Berlin, Germany
- German Cancer Consortium (DKTK), Berlin, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
| | - Annette Künkele
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- German Cancer Consortium (DKTK), Berlin, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
- Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany
| | - Matthias Fischer
- Department of Experimental Pediatric Oncology, Center for Molecular Medicine Cologne, 50931, Cologne, Germany
| | - Angelika Eggert
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- German Cancer Consortium (DKTK), Berlin, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
- Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany
| | - Charlotte Kloft
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Kelchstr.31, 12169, Berlin, Germany
| | - Anton George Henssen
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
- Experimental and Clinical Research Center (ECRC) of the Charité and Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125, Berlin, Germany
- German Cancer Consortium (DKTK), Berlin, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
- Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany
| | - Michael Boettcher
- Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), 06120, Halle, Germany
| | - Falk Hertwig
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Nils Blüthgen
- Institute of Pathology, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany
- IRI Life Sciences, Humboldt University Berlin, 10115, Berlin, Germany
- German Cancer Consortium (DKTK), Berlin, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
- Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany
| | - Louis Chesler
- Paediatric Solid Tumour Biology and Therapeutics Team, Clinical Division and Cancer Therapeutics Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
| | - Johannes Hubertus Schulte
- Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
- German Cancer Consortium (DKTK), Berlin, Germany.
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
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Thirunavukkarasu B, Roy PS, Gupta K, Sekar A, Bansal D. Infantile Inflammatory Myofibroblastic Tumor of Spleen. Fetal Pediatr Pathol 2022; 41:475-479. [PMID: 33095087 DOI: 10.1080/15513815.2020.1836098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
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.
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Affiliation(s)
| | - Pritam Singha Roy
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kirti Gupta
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Aravind Sekar
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Deepak Bansal
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Huang K, Zhao P, Zhao J, Zhao P, Yang J. A unique case of inflammatory myofibroblastic tumor of the liver manifesting with biloma: A case report. Oncol Lett 2022; 24:227. [PMID: 35720485 PMCID: PMC9185161 DOI: 10.3892/ol.2022.13348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 04/22/2022] [Indexed: 02/05/2023] Open
Abstract
Anaplastic lymphoma kinase (ALK)-negative hepatic inflammatory myofibroblastic tumors (IMTs) harboring the ETS variant transcription factor 6-neurotrophic receptor tyrosine kinase 3 (ETV6-NTRK3) fusion gene and manifesting with biloma are extremely rare, and their biological behavior is unclear. The present study reports the case of a 45-year-old female with ALK-negative IMT of the liver harboring the ETV6-NTRK3 fusion gene and manifesting with biloma. Computed tomography of the abdomen confirmed the lesions to be a low-density mass, measuring 11.2×8.5×10.5 cm, located in the left lobe of the liver, and a lower-density mass, measuring 8.5×6.1×5.9 cm, located in the interior of the tumor. As the suspicion of a malignancy remained high, surgical resection of the left hepatic lobe, including the tumor, was undertaken. Intraoperatively, a tumor (12×10×9 cm), with an unclear boundary, incomplete capsule and fish-like texture, was found in the left lateral lobe of the liver, and a biloma, measuring 8×6 cm, was identified inside the tumor. Pathological examination revealed spindle cell proliferation with infiltration of chronic inflammatory cells and mucinous degeneration. Immunohistochemical studies showed negativity for ALK, CD117, CD34, discovered on GIST-1, desmin, smooth muscle actin, S-100, CD21, pan-cytokeratin, epithelial membrane antigen, CD23 and CD35, but positivity for vimentin staining, and 5% Ki-67-positive cells. Fluorescence in situ hybridization studies assessing characteristic genetic rearrangements using ALK, RET, ROS1, MDM2, MGEA5 and ETV6 break-apart assays, revealed the presence of the ETV6-NTRK3 fusion oncogene and negativity for ALK, RET, ROS1, MDM2 and MGEA5. The patient was discharged 7 days post-operatively, without any adjuvant treatment. No recurrence of symptoms was noted at the 3-year follow-up. To the best of our knowledge, this is the first report of biloma in an ALK-negative IMT of the liver, which may increase our understanding of hepatic IMT.
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Affiliation(s)
- Kun Huang
- Department of General Surgery, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, Sichuan 621000, P.R. China
| | - Pingwu Zhao
- Department of General Surgery, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, Sichuan 621000, P.R. China
| | - Jiangying Zhao
- Department of Pathology, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, Sichuan 621000, P.R. China
| | - Pan Zhao
- Department of General Surgery, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, Sichuan 621000, P.R. China
| | - Jian Yang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610000, P.R. China
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Yu H, Zhang C, Tong N, Wang X, Wang L, Gong H, Liu X, Zhou Z. Intraocular myofibroblastoma tumour of the ciliary body: a case report and literature review. BMC Ophthalmol 2022; 22:200. [PMID: 35501775 PMCID: PMC9063157 DOI: 10.1186/s12886-022-02411-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 04/18/2022] [Indexed: 11/18/2022] Open
Abstract
Background Inflammatory Myofibroblastoma Tumors (IMTs) are extremely tumour rare in the intraocular. Case presentation A ciliary body tumor was found under slit lamp biomicroscopy in a 55-year-old male first diagnosed with cataract. Then this patient underwent trans-sclera resection via partial lamellar sclerouvectomy and par plans vitrectomy to remove the mass. Hematoxylin and eosin (HE) staining and immunohistochemistry findings showed that the characteristics of the tumor were consistent with IMT. Conclusions We reported a rare case of intraocular IMT, which is confirmed by H&E staining, and IHC positive staining for Vimentin, Desmin and ALK, while negative staining for SMA, S-100, ki-67, CK, CD68, and calponin.
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Affiliation(s)
- He Yu
- Department of Ophthalmology, Qingdao Municipal Hospital, 5 Middle Donghai Road, Shinan District, Qingdao, Shandong, China.,Department of Ophthalmology, Dalian No,3 People's Hospital, No. 40 Qianshan Road,Ganjingzi District, Dalian, Liaoning, China
| | - Caixin Zhang
- Department of Pathology, Qingdao Municipal Hospital, No.5 Donghai Middle Road, Shinan District, Qingdao, Shandong, China
| | - Nianting Tong
- Department of Ophthalmology, Qingdao Municipal Hospital, 5 Middle Donghai Road, Shinan District, Qingdao, Shandong, China
| | - Xiu Wang
- Department of Ophthalmology, Qingdao Municipal Hospital, 5 Middle Donghai Road, Shinan District, Qingdao, Shandong, China
| | - Liangyu Wang
- Department of Ophthalmology, Qingdao Municipal Hospital, 5 Middle Donghai Road, Shinan District, Qingdao, Shandong, China
| | - Huimin Gong
- Department of Ophthalmology, Qingdao Municipal Hospital, 5 Middle Donghai Road, Shinan District, Qingdao, Shandong, China
| | - Xin Liu
- Department of Ophthalmology, Dalian No,3 People's Hospital, No. 40 Qianshan Road,Ganjingzi District, Dalian, Liaoning, China
| | - Zhanyu Zhou
- Department of Ophthalmology, Qingdao Municipal Hospital, 5 Middle Donghai Road, Shinan District, Qingdao, Shandong, China.
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Lee CS, Kim JS, Rodriguez R, Krell RW. Anaplastic Lymphoma Kinase Positive Mesenteric Inflammatory Myofibroblastic Tumor in Adult Woman. Cureus 2022; 14:e24422. [PMID: 35637807 PMCID: PMC9126854 DOI: 10.7759/cureus.24422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/23/2022] [Indexed: 11/25/2022] Open
Abstract
Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms containing spindle cells and inflammatory components that can be locally aggressive. They have unclear biological behavior and may recur after resection. A 31-year-old woman presented with three months of cough, fatigue, weight loss, abdominal pain, anemia, and elevated inflammatory markers. CT showed a large well-circumscribed enhancing mass in the right colic mesentery. The patient underwent a laparoscopic right colectomy. Pathologic review showed fascicular spindle cells with admixed chronic inflammatory cells. Cells stained diffusely positive for SMA and anaplastic lymphoma kinase (ALK), diagnostic of an IMT. Post-operatively, the patient reported symptom resolution and had normalization of lab values. She remains disease-free at 20 months. IMT is rare in adults, accounting for 0.7%-1.0% of lung tumors. Up to 30% of patients present with elevated inflammatory markers. On imaging, IMTs are soft tissue masses with variable enhancement and fibrosis, often suspected to be malignant neoplasms. Up to 80% of IMTs are driven by altered tyrosine kinase signaling and half of IMTs express ALK, which may be treated in unresectable/recurrent cases using ALK-inhibitors. IMT may recur in 10%-15% of patients. The roles of adjuvant treatments are unclear given the rarity and unpredictable biological behavior. Long-term follow-up with regular radiologic and laboratory surveillance is recommended given possible local recurrence. IMTs are best managed in a multidisciplinary setting given their unpredictable nature. Surgery is the mainstay of IMT treatment with long-term control expected in >80% of adult patients.
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Dashti NK, Dermawan J, Schoolmeester JK, Halling KC, Antonescu CR. A novel
WWTR1
::
AFF2
fusion in an intra‐abdominal soft tissue sarcoma with associated endometriosis. Genes Chromosomes Cancer 2022; 61:497-502. [PMID: 35429182 PMCID: PMC9233893 DOI: 10.1002/gcc.23045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 03/25/2022] [Accepted: 04/06/2022] [Indexed: 11/08/2022] Open
Abstract
Application of molecular testing in clinical practice has led to significant advances in the classification of soft tissue sarcomas. Despite remarkable progress, there are still challenging cases that remain unclassified. In this study, we present an unusual spindle cell sarcoma arising in the abdominal cavity of a 37-year-old female. An extensive panel of immunostains was nonspecific for a line of differentiation and the tumor was subjected to targeted RNA sequencing for further classification. The findings showed a novel WWTR1::AFF2 fusion, which was further confirmed by break-apart FISH analysis for WWTR1 gene rearrangement. The tumor was attached to the wall of sigmoid colon and showed a highly cellular proliferation of plump spindle to epithelioid cells arranged in intersecting fascicles. Areas of extensive endometriosis were identified adjacent to the tumor. The immunoprofile was significant for reactivity with desmin, calponin, WT-1, ER, and PR, while negative for CD10, SMA, caldesmon, pan-keratin, ALK, CD117, and S100. The patient is alive and well after 11 months of follow-up. The exact histogenesis of this sarcoma remains unclear, however, the presence of adjacent endometriosis and coexpression of WT1/ER/PR raises the possibility of an unusual endometrioid stromal sarcoma, occurring outside the GYN tract. Additional cases are needed to establish the recurrent potential of this fusion event and to better define its pathogenesis and clinical behavior.
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Affiliation(s)
- Nooshin K. Dashti
- Department of Pathology and Laboratory Medicine Cedar‐Sinai Los Angeles California United States
| | - Josephine Dermawan
- Department of Pathology Memorial Sloan Kettering Cancer Center New York New York United States
| | | | - Kevin C. Halling
- Department of Pathology and Laboratory Medicine Mayo Clinic Rochester Minnesota United States
| | - Cristina R. Antonescu
- Department of Pathology Memorial Sloan Kettering Cancer Center New York New York United States
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Gadeyne L, Creytens D, Dekeyser S, Van der Meulen J, Haspeslagh M. Primary Cutaneous Epithelioid Inflammatory Myofibroblastic Sarcoma Harboring RANBP2-ALK Fusion: Report of an Exceptional Case. Am J Dermatopathol 2022; 44:302-305. [PMID: 34816804 DOI: 10.1097/dad.0000000000002096] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
ABSTRACT Inflammatory myofibroblastic tumors are rare soft tissue neoplasms with an uncertain biological behavior, derived from fibroblastic and myofibroblastic cells. In rare cases, a peculiar epithelioid phenotypic variant of this tumor is encountered, named epithelioid inflammatory myofibroblastic sarcoma (EIMS). EIMS has overlapping features with inflammatory myofibroblastic tumor but has been correlated with a more aggressive clinical course, a characteristic nuclear membrane or perinuclear anaplastic lymphoma kinase (ALK) immunostaining pattern and a very specific RANBP2-ALK fusion. To date, EIMS has been reported almost exclusively in the abdominal and pelvic cavity, with the exception of some intrathoracic cases. Herein, we present the first case of primary cutaneous EIMS, confirmed by molecular analysis showing the diagnostic RANBP2-ALK fusion.
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Affiliation(s)
| | - David Creytens
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | - Sam Dekeyser
- Department of Dermatology, General Hospital AZ Maria Middelares, Ghent, Belgium
| | - Joni Van der Meulen
- Molecular Diagnostics Ghent University Hospital (MDG), Ghent University Hospital, Ghent, Belgium; and
- CRIG, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium
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A G H, Kumar S, Singla S, Kurian N. Aggressive Inflammatory Myofibroblastic Tumor of Distal Pancreas: A Diagnostic and Surgical Challenge. Cureus 2022; 14:e22820. [PMID: 35399449 PMCID: PMC8980218 DOI: 10.7759/cureus.22820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/03/2022] [Indexed: 11/05/2022] Open
Abstract
An inflammatory myofibroblastic tumor (IMT) is a rare soft tissue neoplasm of unknown etiology. It is a slow-growing tumor of borderline malignant potential. Distant metastases and recurrence after complete excision are rare. Establishing a preoperative diagnosis is difficult because of its nonspecific clinic-radiological features. Although the majority of cases have been reported in the lungs, it can affect any part of the body. The pancreatic inflammatory myofibroblastic tumor is very rare and only 26 cases have been reported in the medical literature. These tumors mostly arise from the head of the pancreas, whereas occurrence in the body or tail region is rather unusual. Here, we report a case of a 55-year-old male patient with a locally advanced inflammatory myofibroblastic tumor arising from the pancreatic tail. Complete excision of tumor required multi-visceral resection (distal pancreaticosplenectomy with jejunal and colonic segmental resection). The diagnosis of inflammatory myofibroblast tumor was made on the basis of histopathology and immunohistochemistry.
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Wang Z, Geng Y, Yuan LY, Wang MM, Ye CY, Sun L, Dai WP, Zang YS. Durable Clinical Response to ALK Tyrosine Kinase Inhibitors in Epithelioid Inflammatory Myofibroblastic Sarcoma Harboring PRRC2B-ALK Rearrangement: A Case Report. Front Oncol 2022; 12:761558. [PMID: 35237506 PMCID: PMC8882834 DOI: 10.3389/fonc.2022.761558] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/24/2022] [Indexed: 12/21/2022] Open
Abstract
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm and patients with IMT tend to have a favorable outcome after complete surgical resection. However, some tumors of IMT cases have recurred and grown rapidly after successful surgery. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a highly aggressive intra-abdominal IMT variant with epithelioid-to-round cell morphology. Currently, no standard therapy exists for recurrent or invasive IMTs and EIMS, but anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are recommended for those harboring ALK gene rearrangements. We herein report the first case of PRRC2B-ALK fusion associated IMTs with clinical and pathological manifestation matched the diagnosis criteria of EIMS and the durable clinical response of the sequential use of ALK TKIs (crizotinib, alectinib, ceritinib, and lorlatinib). A female patient with EIMS of the greater omentum was suffering from a rapid recurrence after cytoreductive surgery was done. Crizotinib was administered when PRRC2B-ALK fusion was detected, and partial response was achieved. The progression-free survival (PFS) of crizotinib was 5 months. Alectinib was administered based on the results of second next-generation sequencing (NGS) analysis, which identified the secondary mutation ALK R1192P. The best overall response of alectinib treatment was a partial response (PR) and the PFS was 5.5 months. Ceritinib was prescribed as third-line therapy after alectinib resistance with ALK L1196M mutation. PR was achieved and the PFS of ceritinib was 6 months. The patient was taking lorlatinib after ceritinib resistance and achieved a stable disease at 2 months with the PFS more than 5 months. The overall survival was more than two years as of the time of manuscript preparation. We describe an EIMS of greater omentum caused by PRRC2B-ALK fusion gene and showed durable clinical response to the sequential use of ALK TKIs.
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Affiliation(s)
- Zhan Wang
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yan Geng
- Department of Nursing, Shanghai Jing’an District Zhabei Central Hospital, Shanghai, China
| | - Ling-Yan Yuan
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Miao-Miao Wang
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Chen-Yang Ye
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Li Sun
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wei-Ping Dai
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yuan-Sheng Zang
- Department of Medical Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
- *Correspondence: Yuan-Sheng Zang, ; orcid.org/0000-0002-9488-7305
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Bahrani E, Kunder CA, Teng JM, Brown RA, Rieger KE, Novoa RA, Cloutier JM. Spitz nevus with EHBP1-ALK fusion and distinctive membranous localization of ALK. J Cutan Pathol 2022; 49:584-588. [PMID: 35113459 DOI: 10.1111/cup.14209] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/26/2022] [Accepted: 01/30/2022] [Indexed: 11/30/2022]
Abstract
ALK rearrangements define a histopathologically distinctive but diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of other genes, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13-year-old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next-generation RNA sequencing revealed an in-frame EHBP1-ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5' ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK-rearranged melanocytic tumors. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Eman Bahrani
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Christian A Kunder
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Joyce M Teng
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.,Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Ryanne A Brown
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.,Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.,Department of Pathology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Kerri E Rieger
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.,Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Roberto A Novoa
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.,Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Jeffrey M Cloutier
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
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Ruan H, Yan BD, Tao YM, Ran X, Li SS. Endoscopic therapy combined with photodynamic therapy for intratracheal inflammatory myofibroblastic tumor. Photodiagnosis Photodyn Ther 2022; 38:102784. [DOI: 10.1016/j.pdpdt.2022.102784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/17/2022] [Accepted: 02/23/2022] [Indexed: 11/25/2022]
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Park JW, Han SH, Kim DK. [Inflammatory Myofibroblastic Tumor Misdiagnosed as Intrahepatic Cholangiocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2022; 79:41-44. [PMID: 35086972 DOI: 10.4166/kjg.2021.146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/28/2021] [Accepted: 11/28/2021] [Indexed: 11/03/2022]
Abstract
An inflammatory myofibroblastic tumor (IMT) is a rare tumor that is currently classified as an intermediate cancer according to the World Health Organization classification system. The pathophysiology of its occurrence is still unknown. Imaging tests, such as CT or MRI, can be helpful in diagnosis, but the final diagnosis is confirmed by a pathological examination through a biopsy and immunohistochemistry stain. The patient, in this case, presented an asymptomatic intrahepatic mass discovered incidentally on an imaging examination. Initially, intrahepatic cholangiocarcinoma was suspected, but she was finally diagnosed with IMT through a histological examination after a liver resection.
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Affiliation(s)
- Ji Weon Park
- Department of Gastroenterology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
| | - Song Hee Han
- Department of Pathology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
| | - Dong Kyun Kim
- Department of Gastroenterology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
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Chang WI, Lin C, Liguori N, Honeyman JN, DeNardo B, El-Deiry W. Molecular Targets for Novel Therapeutics in Pediatric Fusion-Positive Non-CNS Solid Tumors. Front Pharmacol 2022; 12:747895. [PMID: 35126101 PMCID: PMC8811504 DOI: 10.3389/fphar.2021.747895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/03/2021] [Indexed: 12/31/2022] Open
Abstract
Chromosomal fusions encoding novel molecular drivers have been identified in several solid tumors, and in recent years the identification of such pathogenetic events in tumor specimens has become clinically actionable. Pediatric sarcomas and other rare tumors that occur in children as well as adults are a group of heterogeneous tumors often with driver gene fusions for which some therapeutics have already been developed and approved, and others where there is opportunity for progress and innovation to impact on patient outcomes. We review the chromosomal rearrangements that represent oncogenic events in pediatric solid tumors outside of the central nervous system (CNS), such as Ewing Sarcoma, Rhabdomyosarcoma, Fibrolamellar Hepatocellular Carcinoma, and Renal Cell Carcinoma, among others. Various therapeutics such as CDK4/6, FGFR, ALK, VEGF, EGFR, PDGFR, NTRK, PARP, mTOR, BRAF, IGF1R, HDAC inhibitors are being explored among other novel therapeutic strategies such as ONC201/TIC10.
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Affiliation(s)
- Wen-I Chang
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- Pediatric Hematology/Oncology, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, RI, United States
- *Correspondence: Wen-I Chang, ; Wafik El-Deiry,
| | - Claire Lin
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI, United States
| | - Nicholas Liguori
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI, United States
| | - Joshua N. Honeyman
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, RI, United States
- Pediatric Surgery, The Warren Alpert Medical School, Brown University, Providence, RI, United States
| | - Bradley DeNardo
- Pediatric Hematology/Oncology, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, RI, United States
| | - Wafik El-Deiry
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, RI, United States
- Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI, United States
- Hematology/Oncology Division, Department of Medicine, Lifespan Health System and Brown University, Providence, RI, United States
- *Correspondence: Wen-I Chang, ; Wafik El-Deiry,
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