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1
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Judson I, Jones RL, Wong NACS, Dileo P, Bulusu R, Smith M, Almond M. Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines. Br J Cancer 2025; 132:1-10. [PMID: 38840030 PMCID: PMC11723931 DOI: 10.1038/s41416-024-02672-0] [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: 01/09/2024] [Revised: 03/21/2024] [Accepted: 03/25/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND British Sarcoma Group guidelines for the management of GIST were initially informed by those published by the European Society of Clinical Oncology. This update was written by a group of experts to includes a discussion of the highlight improvements in our knowledge of the disease and recent treatment developments. The guidelines include sections on Incidence, Aetiology, Diagnosis, including risk assessment, Treatment and Follow-up. METHODS A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Areas of uncertainty are indicated appropriately. CONCLUSION Guidelines represent a consensus view of current best clinical practice. Where appropriate, key recommendations are given and the levels of evidence and strength of recommendation gradings are those used by the European Society for Medical Oncology (ESMO).
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Affiliation(s)
- Ian Judson
- The Institute of Cancer Research, London, UK.
| | | | | | | | | | - Myles Smith
- Royal Marsden NHS Foundation Trust, London, UK
| | - Max Almond
- Birmingham University Hospitals, Birmingham, UK
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2
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Gabellone S, Vanni S, Fausti V, Miserocchi G, Liverani C, Spadazzi C, Cocchi C, Calabrese C, Cavaliere D, Pacilio CA, Ercolani G, Pieri F, Gurrieri L, Riva N, Jones R, De Vita A. Exploring nanotechnology solutions for improved outcomes in gastrointestinal stromal tumors. Heliyon 2024; 10:e40596. [PMID: 39687122 PMCID: PMC11647801 DOI: 10.1016/j.heliyon.2024.e40596] [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: 11/21/2023] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Objectives Gastrointestinal stromal tumors, the most prevalent mesenchymal tumors (80 %) of the gastrointestinal tract, comprise less than 1 % of all gastrointestinal neoplasms and about 5 % of all sarcomas. Despite their rarity, Gastrointestinal stromal tumors present diverse clinical manifestations, anatomic locations, histological subtypes, and prognostic outcomes. Methods This scoping review comprehensively explores the epidemiology, clinical characteristics, diagnostic and prognostic modalities, as well as new therapeutic options for Gastrointestinal stromal tumors. Results A particular focus is placed on the promising role of bio-nanomaterials as multifunctional agents for drug delivery and 3D tumor microenvironment modeling. Bio-nanomaterials offer promising opportunities for targeted drug delivery, overcoming treatment resistance, and improving therapeutic efficacy. Conclusion Despite significant advancements, Gastrointestinal stromal tumors remain a complex clinical entity with ongoing challenges. The integration of nanotechnology into Gastrointestinal stromal tumors management offers the potential to enhance patient outcomes. Future studies should prioritize the development and evaluation of nanomaterial-based therapies in clinical trials to facilitate the translation of laboratory discoveries into real-world clinical applications.
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Affiliation(s)
- Sofia Gabellone
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Silvia Vanni
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Valentina Fausti
- Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Giacomo Miserocchi
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Chiara Liverani
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Chiara Spadazzi
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Claudia Cocchi
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Chiara Calabrese
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Davide Cavaliere
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, 47121, Forlì, Italy
| | | | - Giorgio Ercolani
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, 47121, Forlì, Italy
| | - Federica Pieri
- Pathology Unit, “Morgagni-Pierantoni” Hospital, 47121, Forlì, Italy
| | - Lorena Gurrieri
- Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Nada Riva
- Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
| | - Robin Jones
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, SW3 6JJ, London, UK
| | - Alessandro De Vita
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy
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3
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Wang X, Shou C, Zhu K, Yang W, Yu J. New Abdominal Mass After Surgery for Gastrointestinal Stromal Tumor: Desmoid-Type Fibromatosis Difficult to Distinguish from Mesenchymal Tumor - A Case Report. Int Med Case Rep J 2024; 17:965-969. [PMID: 39559297 PMCID: PMC11572469 DOI: 10.2147/imcrj.s488459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/01/2024] [Indexed: 11/20/2024] Open
Abstract
A new lump in patients with a history of gastrointestinal stromal tumor (GIST) may indicate resistance to medication and recurrence. It is important to monitor for recurrence or metastasis after surgery for GIST, especially in cases of high-risk GIST, as it determines the subsequent treatment. However, it is difficult to differentiate between GIST and DF by imaging. Tissue biopsy and final diagnosis through pathological analysis are usually required. Here, we report 2 cases of primary diagnosis with high-risk GIST and suspected tumor recurrence during Imatinib treatment. The mass was not located where the previous GIST lesion had been. After the complete excision of the mass through laparoscopic surgery, the pathological findings revealed that it was not a recurrence of GIST, but a desmoid-type fibromatosis.
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Affiliation(s)
- Xiaodong Wang
- Gastroenterology Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Chunhui Shou
- Gastroenterology Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Kankai Zhu
- Gastroenterology Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Weili Yang
- Gastroenterology Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Jiren Yu
- Gastroenterology Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
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4
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Ibrahim A, Montgomery EA. Gastrointestinal Stromal Tumors: Variants and Some Pitfalls That They Create. Adv Anat Pathol 2024; 31:354-363. [PMID: 39466697 DOI: 10.1097/pap.0000000000000463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
The diagnosis of gastrointestinal stromal tumors (GISTs) is generally straightforward using a combination of histologic evaluation and pertinent immunohistochemical staining with CD117/kit and DOG-1 (discovered on GIST) antibodies. However, this tumor can be challenging in cases with an unusual morphology, in limited biopsies, for those in uncommon sites, post-treatment, and when other neoplasms express CD117/kit and DOG-1, thereby mimicking GIST. Finding epithelioid GISTs in the stomach in younger patients should prompt testing for succinate dehydrogenase (SHD)-deficiency using immunohistochemical staining for subunit B (SDHB). However, SDH-deficient GISTs can also arise in older patients, or as part of the Carney triad or Carney-Stratakis syndrome. GISTs with PDGFRA mutations can also prove difficult if they lack kit expression. It is also important to consider morphologic and immunophenotypic changes associated with treatment, including the potential absence of kit expression, particularly in GISTs that have metastasized. Therefore, obtaining clinical information regarding prior therapy with a tyrosine kinase inhibitor (TKI) is crucial.
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Affiliation(s)
- Ammoura Ibrahim
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL
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5
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Renne SL, Cammelli M, Santori I, Tassan-Mangina M, Samà L, Ruspi L, Sicoli F, Colombo P, Terracciano LM, Quagliuolo V, Cananzi FCM. True Mitotic Count Prediction in Gastrointestinal Stromal Tumors: Bayesian Network Model and PROMETheus (Preoperative Mitosis Estimator Tool) Application Development. J Med Internet Res 2024; 26:e50023. [PMID: 39437385 PMCID: PMC11538881 DOI: 10.2196/50023] [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: 06/16/2023] [Revised: 05/14/2024] [Accepted: 07/21/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) present a complex clinical landscape, where precise preoperative risk assessment plays a pivotal role in guiding therapeutic decisions. Conventional methods for evaluating mitotic count, such as biopsy-based assessments, encounter challenges stemming from tumor heterogeneity and sampling biases, thereby underscoring the urgent need for innovative approaches to enhance prognostic accuracy. OBJECTIVE The primary objective of this study was to develop a robust and reliable computational tool, PROMETheus (Preoperative Mitosis Estimator Tool), aimed at refining patient stratification through the precise estimation of mitotic count in GISTs. METHODS Using advanced Bayesian network methodologies, we constructed a directed acyclic graph (DAG) integrating pertinent clinicopathological variables essential for accurate mitotic count prediction on the surgical specimen. Key parameters identified and incorporated into the model encompassed tumor size, location, mitotic count from biopsy specimens, surface area evaluated during biopsy, and tumor response to therapy, when applicable. Rigorous testing procedures, including prior predictive simulations, validation utilizing synthetic data sets were employed. Finally, the model was trained on a comprehensive cohort of real-world GIST cases (n=80), drawn from the repository of the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, with a total of 160 cases analyzed. RESULTS Our computational model exhibited excellent diagnostic performance on synthetic data. Different model architecture were selected based on lower deviance and robust out-of-sample predictive capabilities. Posterior predictive checks (retrodiction) further corroborated the model's accuracy. Subsequently, PROMETheus was developed. This is an intuitive tool that dynamically computes predicted mitotic count and risk assessment on surgical specimens based on tumor-specific attributes, including size, location, surface area, and biopsy-derived mitotic count, using posterior probabilities derived from the model. CONCLUSIONS The deployment of PROMETheus represents a potential advancement in preoperative risk stratification for GISTs, offering clinicians a precise and reliable means to anticipate mitotic counts on surgical specimens and a solid base to stratify patients for clinical studies. By facilitating tailored therapeutic strategies, this innovative tool is poised to revolutionize clinical decision-making paradigms, ultimately translating into improved patient outcomes and enhanced prognostic precision in the management of GISTs.
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Affiliation(s)
- Salvatore Lorenzo Renne
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Manuela Cammelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Ilaria Santori
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Marta Tassan-Mangina
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Laura Samà
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Laura Ruspi
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Federico Sicoli
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Piergiuseppe Colombo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Luigi Maria Terracciano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Vittorio Quagliuolo
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Ferdinando Carlo Maria Cananzi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
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Mousavi S, Ono Y, VanderLaan PA, Guzmán-Arocho YD. Gastrointestinal stromal tumors in fine-needle aspiration biopsies. Diagn Cytopathol 2024; 52:575-581. [PMID: 38396207 DOI: 10.1002/dc.25285] [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: 01/15/2024] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 02/25/2024]
Abstract
Gastrointestinal stromal tumors (GISTs), although rare, are the most common mesenchymal neoplasms of the gastrointestinal tract. Their potential for malignancy underscores the significance of identifying them through cytomorphologic findings and pertinent immunohistochemical markers. GISTs can emerge anywhere along the gastrointestinal tract with a predilection for the stomach. The clinical manifestations vary from nonspecific abdominal symptoms to incidental discovery during diagnostic interventions for unrelated signs and symptoms. Cytologically, GIST aspirates contain spindle or epithelioid cells with immunoreactivity for CD117/c-KIT, DOG-1, and CD34. Molecularly, KIT or PDGFRA mutations are prevalent, guiding targeted therapy with tyrosine kinase inhibitors. Distinct subtypes like succinate dehydrogenase-deficient GISTs pose challenges, often affecting younger individuals and displaying unique features. Histologically, GISTs are graded by mitotic rates, aiding prognostication. Distinguishing GISTs from similar entities is pivotal, necessitating attention to their immunostaining patterns for making an accurate diagnosis and molecular alterations for effectively planning treatment. Common differential diagnoses include leiomyoma, schwannoma, and solitary fibrous tumor. This article presents a classic GIST case and showcases relatively simple diagnostic clues for identifying similar lesions that may occur in diverse locations.
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Affiliation(s)
- Seyedreza Mousavi
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Yuho Ono
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Paul A VanderLaan
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Yaileen D Guzmán-Arocho
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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7
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Pham AT, Pham AT, Truong CM, Nguyen TH, Trinh PH. Primary gastrointestinal stromal tumor of the liver: a case report. Ann Med Surg (Lond) 2024; 86:4284-4290. [PMID: 38989195 PMCID: PMC11230766 DOI: 10.1097/ms9.0000000000002228] [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: 03/22/2024] [Accepted: 05/19/2024] [Indexed: 07/12/2024] Open
Abstract
Introduction and importance Primary gastrointestinal stromal tumors of the liver are exceedingly rare entities, presenting diagnostic and therapeutic challenges. The authors present a case of a 64-year-old male with a primary gastrointestinal stromal tumor (GIST) of the liver, emphasizing the importance of comprehensive diagnostic evaluation and multidisciplinary management in such uncommon cases. Case presentation The patient presented with persistent hypochondriac pain, leading to the discovery of a hepatic mass. Diagnostic work-ups, including imaging studies and biopsy, confirmed the diagnosis of primary GIST in the liver. Following thorough multidisciplinary consultation, the patient underwent right anterior segmentectomy of the liver, performed by our experienced surgeon. Postoperative pathology confirmed the diagnosis of GIST, and the patient was advised to use adjuvant imatinib. Clinical discussion Primary GISTs of the liver pose diagnostic challenges due to their rarity and varied clinical presentations. Imaging modalities, immunohistochemistry, and molecular genotyping are crucial in accurate diagnosis and treatment planning. Surgical resection remains the cornerstone of treatment for localized GISTs, with adjuvant therapy considered based on recurrence risk factors and molecular characteristics. Conclusion This case highlights the need for multidisciplinary consultation in managing primary GISTs of the liver. Accurate diagnosis, surgical expertise, and personalized adjuvant therapy are crucial for better patient outcomes. Further research is necessary to enhance our understanding of prognostic factors and treatment strategies for these rare tumors.
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Affiliation(s)
| | - Anh The Pham
- Hepatobiliary and Pancreatic Surgery, Vietnam National Cancer Hospital, 30 Cau Buou, Tan Trieu, Hanoi, Vietnam
| | - Cuong Manh Truong
- Hepatobiliary and Pancreatic Surgery, Vietnam National Cancer Hospital, 30 Cau Buou, Tan Trieu, Hanoi, Vietnam
| | | | - Phuong Huy Trinh
- Hepatobiliary and Pancreatic Surgery, Vietnam National Cancer Hospital, 30 Cau Buou, Tan Trieu, Hanoi, Vietnam
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Hirota S, Tateishi U, Nakamoto Y, Yamamoto H, Sakurai S, Kikuchi H, Kanda T, Kurokawa Y, Cho H, Nishida T, Sawaki A, Ozaka M, Komatsu Y, Naito Y, Honma Y, Takahashi F, Hashimoto H, Udo M, Araki M, Nishidate S. English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology. Int J Clin Oncol 2024; 29:647-680. [PMID: 38609732 PMCID: PMC11130037 DOI: 10.1007/s10147-024-02488-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 02/12/2024] [Indexed: 04/14/2024]
Abstract
The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.
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Affiliation(s)
- Seiichi Hirota
- Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
| | - Ukihide Tateishi
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hidetaka Yamamoto
- Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shinji Sakurai
- Department of Diagnostic Pathology, Japan Community Healthcare Organization Gunma Central Hospital, Maebashi, Japan
| | - Hirotoshi Kikuchi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Toshirou Nishida
- Department of Surgery, Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan
| | - Akira Sawaki
- Department of Medical Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshito Komatsu
- Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan
| | - Yoichi Naito
- Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoshitaka Honma
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Fumiaki Takahashi
- Department of Information Science, Iwate Medical University, Morioka, Japan
| | | | - Midori Udo
- Nursing Department, Osaka Police Hospital, Osaka, Japan
| | - Minako Araki
- Association of Chubu GIST Patients and Their Families, Nagoya, Japan
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Challa B, Jones D, Kim AC, D'Souza DM, Esnakula AK. NTRK-rearranged mesenchymal tumour in oesophagus with DOG1 immunohistochemical expression: is it a gastrointestinal stromal tumour? Pathology 2024; 56:602-604. [PMID: 38101957 DOI: 10.1016/j.pathol.2023.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 09/05/2023] [Accepted: 09/19/2023] [Indexed: 12/17/2023]
Affiliation(s)
- Bindu Challa
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Daniel Jones
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; James Molecular Pathology Laboratory, Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Alex C Kim
- Department of Surgery, Division of Surgical Oncology, James Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Desmond M D'Souza
- Division of Thoracic Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Ashwini Kumar Esnakula
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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Adle-Biassette H, Ricci R, Martin A, Martini M, Ravegnini G, Kaci R, Gélébart P, Poirot B, Sándor Z, Lehman-Che J, Tóth E, Papp B. Sarco/endoplasmic reticulum calcium ATPase 3 (SERCA3) expression in gastrointestinal stromal tumours. Pathology 2024; 56:343-356. [PMID: 38184384 DOI: 10.1016/j.pathol.2023.10.012] [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: 07/24/2023] [Accepted: 10/18/2023] [Indexed: 01/08/2024]
Abstract
Accurate characterisation of gastrointestinal stromal tumours (GIST) is important for prognosis and the choice of targeted therapies. Histologically the diagnosis relies on positive immunostaining of tumours for KIT (CD117) and DOG1. Here we report that GISTs also abundantly express the type 3 Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA3). SERCA enzymes transport calcium ions from the cytosol into the endoplasmic reticulum and play an important role in regulating the intensity and the periodicity of calcium-induced cell activation. GISTs from various localisations, histological and molecular subtypes or risk categories were intensely immunopositive for SERCA3 with the exception of PDGFRA-mutated cases where expression was high or moderate. Strong SERCA3 expression was observed also in normal and hyperplastic interstitial cells of Cajal. Decreased SERCA3 expression in GIST was exceptionally observed in a zonal pattern, where CD117 staining was similarly decreased, reflecting clonal heterogeneity. In contrast to GIST, SERCA3 immunostaining of spindle cell tumours and other gastrointestinal tumours resembling GIST was negative or weak. In conclusion, SERCA3 immunohistochemistry may be useful for the diagnosis of GIST with high confidence, when used as a third marker in parallel with KIT and DOG1. Moreover, SERCA3 immunopositivity may be particularly helpful in cases with negative or weak KIT or DOG1 staining, a situation that may be encountered de novo, or during the spontaneous or therapy-induced clonal evolution of GIST.
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Affiliation(s)
- Homa Adle-Biassette
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Lariboisière, and Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France; INSERM NeuroDiderot, DMU DREAM, France
| | - Riccardo Ricci
- Department of Pathology, Università Cattolica del Sacro Cuore, Rome, Italy; UOC di Anatomia Patologica, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy
| | - Antoine Martin
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Paris, France; Inserm UMR U978, Université Sorbonne Paris Nord, Alliance Sorbonne Paris Cité, Labex Inflamex, Bobigny, France
| | - Maurizio Martini
- Dipartimento di patologia umana dell'adulto e dell'età evolutiva 'Gaetano Barresi' Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy
| | - Gloria Ravegnini
- Department of Pharmacy and Biotechnology (FaBit), University of Bologna, Bologna, Italy
| | - Rachid Kaci
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Lariboisière, and Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France
| | - Pascal Gélébart
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Brigitte Poirot
- Molecular Oncology Unit, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Zsuzsanna Sándor
- Department of Pathology, National Institute of Oncology, Budapest, Hungary
| | - Jacqueline Lehman-Che
- Molecular Oncology Unit, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM UMR U976, Hôpital Saint-Louis, Paris, France; Institut de Recherche Saint-Louis, Université de Paris, France
| | - Erika Tóth
- Department of Pathology, National Institute of Oncology, Budapest, Hungary
| | - Bela Papp
- INSERM UMR U976, Hôpital Saint-Louis, Paris, France; Institut de Recherche Saint-Louis, Université de Paris, France; CEA, DRF-Institut Francois Jacob, Department of Hemato-Immunology Research, Hôpital Saint-Louis, Paris, France.
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Sharma G, Kamboj M, Narwal A, Keerthika R, Devi A, Vijayakumar G. Diagnostic Utility of Expression Pattern of S100/Mammaglobin/SOX10/DOG 1 Immunohistochemistry in Differentiation of Secretory and Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis. Indian J Otolaryngol Head Neck Surg 2024; 76:208-218. [PMID: 38440438 PMCID: PMC10908910 DOI: 10.1007/s12070-023-04127-z] [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: 07/14/2023] [Accepted: 07/28/2023] [Indexed: 03/06/2024] Open
Abstract
Secretory carcinoma (SC) is a relatively new disease entity, separate from acinic cell carcinoma (AciCC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and AciCC remain ambiguous. Genetic diversity makes its diagnosis complicated. In this regard combined expression of immunohistochemistry markers S100/Mammaglobin/SOX10 and DOG1 is need of the hour as alternative methodology. The current systematic review was to investigate the diagnostic utility of combined immunohistochemical expression of S100/Mammaglobin/SOX10/DOG1 in distinction of SC from AciCC histologically. An electronic search of databases was carried out using MEDLINE by PubMed, Google scholar, Scopus and Web of science. Articles inclusive of SC and AciCC were assessed with S100/Mammaglobin/SOX10/DOG1 immunohistochemistry and their predominant expression pattern, predictive values, sensitivity and specificity were gathered. Fourteen eligible articles were analysed, which revealed predominant immunostaining pattern of S100 + /Mammaglobin + /SOX10 + /DOG1- by nearly all ETV6::NTRK3 fusion prevalent SCs alongside with other gene fusions like RET, MET and MAML3 with 98.4% sensitivity as well as 86.1% specificity. The evidence supports that S100/Mammaglobin/SOX10/DOG1 combined immunostaining can serve as a reliable diagnostic method to differentiate secretory from acinic cell carcinoma.
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Affiliation(s)
- Gitika Sharma
- Pandit Bhagwat Dayal Sharma, University of Health Sciences, Oral Pathology and Microbiology, Rohtak, Haryana 124001 India
| | - Mala Kamboj
- Pandit Bhagwat Dayal Sharma, University of Health Sciences, Oral Pathology and Microbiology, Rohtak, Haryana 124001 India
| | - Anjali Narwal
- Pandit Bhagwat Dayal Sharma, University of Health Sciences, Oral Pathology and Microbiology, Rohtak, Haryana 124001 India
| | - R. Keerthika
- Pandit Bhagwat Dayal Sharma, University of Health Sciences, Oral Pathology and Microbiology, Rohtak, Haryana 124001 India
| | - Anju Devi
- Pandit Bhagwat Dayal Sharma, University of Health Sciences, Oral Pathology and Microbiology, Rohtak, Haryana 124001 India
| | - Gopikrishnan Vijayakumar
- Pandit Bhagwat Dayal Sharma, University of Health Sciences, Oral Pathology and Microbiology, Rohtak, Haryana 124001 India
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12
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Sasa K, Son R, Oguchi A, Ashizawa K, Hasegawa N, Kubota D, Suehara Y, Takagi T, Okubo T, Akaike K, Sugimoto K, Takahashi M, Sakamoto K, Hashimoto T, Mine S, Fukunaga T, Ishijima M, Hayashi T, Yao T, Murakawa Y, Saito T. NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts. Sci Rep 2024; 14:768. [PMID: 38191907 PMCID: PMC10774370 DOI: 10.1038/s41598-024-51211-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 01/02/2024] [Indexed: 01/10/2024] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.
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Affiliation(s)
- Keita Sasa
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
| | - Raku Son
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Akiko Oguchi
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Karin Ashizawa
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Nobuhiko Hasegawa
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
| | - Daisuke Kubota
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshiyuki Suehara
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
| | - Tatsuya Takagi
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
| | - Taketo Okubo
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
| | - Keisuke Akaike
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
- Department of Orthopaedic Surgery, Yamanashi Central Hospital, Yamanashi, Japan
| | - Kiichi Sugimoto
- Department of Coloproctological Surgery, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan
| | - Makoto Takahashi
- Department of Coloproctological Surgery, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan
| | - Takashi Hashimoto
- Department of Upper Gastroenterological Surgery, Juntendo University Hospital, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Shinji Mine
- Department of Upper Gastroenterological Surgery, Juntendo University Hospital, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Tetsu Fukunaga
- Department of Upper Gastroenterological Surgery, Juntendo University Hospital, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Muneaki Ishijima
- Department of Medicine for Orthopaedics and Motor Organ, Juntendo University School of Medicine, Tokyo, Japan
- Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan
| | - Takuo Hayashi
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yasuhiro Murakawa
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
- Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
- IFOM ETS - the AIRC Institute of Molecular Oncology, Milan, Italy
| | - Tsuyoshi Saito
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
- Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
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13
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Gravina AG, Pellegrino R, Romeo M, Cipullo M, Lucà S, Panarese I, Federico A. Vanek's Tumour as a Rare Cause of Dyspeptic Syndrome in a Patient with Primary Biliary Cholangitis: A Case Report. Rev Recent Clin Trials 2024; 19:273-279. [PMID: 39075956 DOI: 10.2174/0115748871308542240708075537] [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: 02/04/2024] [Revised: 05/11/2024] [Accepted: 06/13/2024] [Indexed: 07/31/2024]
Abstract
BACKGROUND Inflammatory Fibroid Polyp (IFP), also known as Vanek's tumour, is a rare mesenchymal gastrointestinal tumour, potentially causing a wide range of clinical manifestations (even though it can be completely asymptomatic) primarily related to the location of the formation. The available evidence suggests a fundamentally non-neoplastic behaviour of IFP. CASE PRESENTATION A 67-year-old female was presented with persistent dyspepsia despite symptomatic therapy. The patient's medical history included primary biliary cholangitis, managed with ursodeoxycholic acid, non-haemorrhagic uterine fibroids, and right knee arthrosis. Clinical examination revealed mild epigastric tenderness, and esophagogastroduodenoscopy identified a sessile mucosal formation. Histological analysis of biopsy samples revealed a gastric hyperplastic polyp, leading to a subsequent esophagogastroduodenoscopy for polypectomy. The excised specimen confirmed the diagnosis of gastric IFP. Post-polypectomy, the patient experienced progressive symptom amelioration, leading to complete resolution within three weeks. DISCUSSION This case thus describes a rare cause of dyspeptic syndrome associated with the presence of a gastric IFP, promptly managed and resolved after endoscopic removal of the polyp, with no histological signs of neoplasia within the en bloc resected sample. CONCLUSION IFP is a possible and rare cause of dyspeptic syndrome. There remain significant challenges in diagnosing this rare condition, which lacks pathognomonic or specific signs and symptoms of its presence (especially when it causes symptoms). Endoscopy, when feasible, remains a cornerstone in the resective management of such lesions.
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Affiliation(s)
- Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, Naples, 80138, Italy
| | - Raffaele Pellegrino
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, Naples, 80138, Italy
| | - Mario Romeo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, Naples, 80138, Italy
| | - Marina Cipullo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, Naples, 80138, Italy
| | - Stefano Lucà
- Pathology Division, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, 80138, Italy
| | - Iacopo Panarese
- Pathology Division, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, 80138, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, Naples, 80138, Italy
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14
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Shi J, Sun K, Kong F, Shen D. Morphological, immunohistochemical, and genetic analyses of epithelioid gastrointestinal stromal tumors. Ann Diagn Pathol 2023; 67:152208. [PMID: 37696133 DOI: 10.1016/j.anndiagpath.2023.152208] [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: 08/08/2023] [Revised: 08/30/2023] [Accepted: 09/01/2023] [Indexed: 09/13/2023]
Abstract
Epithelioid gastrointestinal stromal tumors (GISTs) are rare and may be confused with other tumors with epithelioid morphology. Therefore, herein, we collected 12 epithelioid GIST samples and summarized their morphological and immunohistochemical characteristics. Through genetic testing, we explored the correlation between morphology and gene mutations. The results showed that eight tumors showed focal or diffuse myxoid stromal changes with less cohesively arranged rhabdoid tumor cells; among these, five showed platelet-derived growth factor receptor alpha gene (PDGFRA) mutations. Signet ring cells with sclerosing stroma and receptor tyrosine kinase type III gene (KIT) mutations were present in two cases, which might be a KIT mutation-associated growth pattern in epithelioid GISTs. Succinate dehydrogenase gene (SDH) mutations were detected in three cases. Simultaneously, PDGFRA mutations were detected in two cases, and the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation was detected in another case. SDH-subunit B (SDHB) expression was partially weak and strongly diffuse in two cases with concurrent PDGFRA and SDHD mutations, respectively. The coexistence of PDGFRA and SDHD mutations may have affected SDHB expression. Altogether, we concluded that PDGFRA mutations may play an important role in co-mutant GIST pathogenesis.
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Affiliation(s)
- Jingli Shi
- Department of Pathology, Peking University People's Hospital, 100044, China
| | - Kunkun Sun
- Department of Pathology, Peking University People's Hospital, 100044, China
| | - Fangzhou Kong
- Department of Pathology, Peking University People's Hospital, 100044, China
| | - Danhua Shen
- Department of Pathology, Peking University People's Hospital, 100044, China.
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15
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Marando A, Di Blasi E, Tucci F, Aquilano MC, Bonoldi E. DOG1 expression in neuroendocrine neoplasms: Potential applications and diagnostic pitfalls. Pathol Res Pract 2023; 248:154623. [PMID: 37331184 DOI: 10.1016/j.prp.2023.154623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 06/13/2023] [Accepted: 06/14/2023] [Indexed: 06/20/2023]
Abstract
Neuroendocrine neoplasms represent a heterogeneous group of rare tumors, more frequently arising from gastroenteropancreatic tract and lungs. At the time of diagnosis, 20% of cases are metastatic, and 10% of cases are considered as cancer of unknown primary origin. Several immunohistochemical markers are routinely used to confirm the neuroendocrine differentiation, first among all Synaptophysin and Chromogranin-A; on the other hand, different immunohistochemical markers are used to establish primary anatomical site, as TTF1, CDX2, Islet-1 and Calcitonin, but no marker is available in order to distinguish among different sites of the digestive tract. DOG1 (discovered on GIST-1) is a gene normally expressed in interstitial cells of Cajal and, in routine practice, DOG1 immunostaining is used in diagnosis of GIST (gastrointestinal stromal tumor). DOG1 expression has been described in several neoplasms other than GIST, both in mesenchymal and epithelial neoplasms. In the present study, DOG1 immunostaining has been performed in a large cohort of neuroendocrine neoplasms, including neuroendocrine tumors and neuroendocrine carcinomas, in order to evaluate frequency, intensity and pattern of expression in different anatomical site and in different tumor grade. DOG1 expression was detected in a large percentage of neuroendocrine tumors, with statistically significant association between DOG1 expression and gastrointestinal tract neuroendocrine tumors. As a consequence, DOG1 could be included in marker panel for the identification of primary site in neuroendocrine metastases of unknown primary origin; moreover, these results recommend careful evaluation of DOG1 expression in gastrointestinal neoplasms, in particular in differential diagnosis between epithelioid GIST and neuroendocrine tumors.
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Affiliation(s)
- A Marando
- Department of Surgical Pathology, Niguarda Hospital, Milano, Italy.
| | - E Di Blasi
- School of Pathology, University of Milan, Milan, Italy
| | - F Tucci
- School of Pathology, University of Milan, Milan, Italy
| | - M C Aquilano
- Department of Surgical Pathology, Niguarda Hospital, Milano, Italy
| | - E Bonoldi
- Department of Surgical Pathology, Niguarda Hospital, Milano, Italy
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16
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Chia WK, Chia PY, Abdul Aziz NH, Shuib S, Mustangin M, Cheah YK, Khong TY, Wong YP, Tan GC. Diagnostic Utility of TSSC3 and RB1 Immunohistochemistry in Hydatidiform Mole. Int J Mol Sci 2023; 24:ijms24119656. [PMID: 37298606 DOI: 10.3390/ijms24119656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted genes. The aim of this study is to determine whether other paternally imprinted genes could also assist in the diagnostic approach of hydatidiform moles. This study comprised of 29 complete moles, 15 partial moles and 17 non-molar abortuses. Immunohistochemical study using the antibodies of paternal-imprinted (RB1, TSSC3 and DOG1) and maternal-imprinted (DNMT1 and GATA3) genes were performed. The antibodies' immunoreactivity was evaluated on various placental cell types, namely cytotrophoblasts, syncytiotrophoblasts, villous stromal cells, extravillous intermediate trophoblasts and decidual cells. TSSC3 and RB1 expression were observed in all cases of partial moles and non-molar abortuses. In contrast, their expression in complete moles was identified in 31% (TSSC3) and 10.3% (RB1), respectively (p < 0.0001). DOG1 was consistently negative in all cell types in all cases. The expressions of maternally imprinted genes were seen in all cases, except for one case of complete mole where GATA3 was negative. Both TSSC3 and RB1 could serve as a useful adjunct to p57 for the discrimination of complete moles from partial moles and non-molar abortuses, especially in laboratories that lack comprehensive molecular service and in cases where p57 staining is equivocal.
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Affiliation(s)
- Wai Kit Chia
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
- Department of Diagnostic Laboratory Services, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
| | - Pik Yuen Chia
- Department of Pathology, Hospital Umum Sarawak, Kuching 93586, Sarawak, Malaysia
| | - Nor Haslinda Abdul Aziz
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
| | - Salwati Shuib
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
- Department of Diagnostic Laboratory Services, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
| | - Muaatamarulain Mustangin
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
| | - Yoke Kqueen Cheah
- Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Teck Yee Khong
- Department of Pathology, Women's and Children's Hospital, Adelaide, SA 5006, Australia
| | - Yin Ping Wong
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
- Department of Diagnostic Laboratory Services, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
| | - Geok Chin Tan
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
- Department of Diagnostic Laboratory Services, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Kuala Lumpur, Malaysia
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17
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Benabdallah W, Ben Othmane M, Ouahchi I, Mestiri S, Belkacem O, Bouassida K, Hmida W, Jaidane M. Primary extragastrointestinal stromal tumor of the prostate: review of the literature and case report. Ann Med Surg (Lond) 2023; 85:1888-1893. [PMID: 37228978 PMCID: PMC10205276 DOI: 10.1097/ms9.0000000000000373] [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: 02/06/2023] [Accepted: 02/25/2023] [Indexed: 05/27/2023] Open
Abstract
The extragastrointestinal stromal tumor (EGIST) is defined as a mesenchymal neoplasm arising from soft tissues outside the gastrointestinal tract, and the prostate is a rare presentation site. Case presentation A 58-year-old man was presented with lower urinary tract symptoms for 6 months. A digital rectal examination revealed a markedly enlarged prostate with a smooth, bulging surface. Prostate-specific antigen density was 0.5 ng/ml. MRI of the prostate showed an enlarged prostatic mass with hemorrhagic necrosis. Transrectal ultrasound-guided prostate biopsy was performed and pathological reports suggested a gastrointestinal stromal tumor. The patient refused radical prostatectomy and received only imatinib treatment. Clinical discussion The diagnosis of EGIST of the prostate is extremely rare and depends on the histopathologic features with immunohistochemical results. The treatment is essentially based on radical prostatectomy, but there are other therapeutic modalities associating surgery with adjuvant or neoadjuvant chemotherapy. For patients refusing surgery, treatment with imatinib alone appears to be a therapeutic solution. Conclusion Despite the rarity, EGIST of the prostate should be included in the differential diagnosis of patients presenting with lower urinary tract symptoms. There is no consensus regarding the treatment of EGIST, and the patients are treated as per the risk stratification.
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Affiliation(s)
| | | | - Ines Ouahchi
- Department of Cytogenetic and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia
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18
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Kashima H, Kikuchi S, Kuroda S, Fujiwara T. Laparoscopic and Endoscopic Cooperative Surgery for Gastric Submucosal Tumor Near Esophagogastric Junction With Sliding Hiatal Hernia. Cureus 2023; 15:e37902. [PMID: 37223198 PMCID: PMC10202676 DOI: 10.7759/cureus.37902] [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] [Accepted: 04/20/2023] [Indexed: 05/25/2023] Open
Abstract
The usefulness of laparoscopic and endoscopic cooperative surgery (LECS) for gastric submucosal tumors in the cardiac region has been reported in recent years. However, LECS for submucosal tumors at the esophagogastric junction with hiatal sliding esophageal hernia has not been reported, and its validity as a treatment method is unknown. The patient was a 51-year-old man with a growing submucosal tumor in the cardiac region. Surgical resection was indicated because a definitive diagnosis of the tumor was not determined. The lesion was a luminal protrusion tumor, located on the posterior wall of the stomach 20 mm from the esophagogastric junction, and had a maximum diameter of 16.3 mm on endoscopic ultrasound examination. Because of the hiatal hernia, the lesion could not be detected from the gastric side by endoscopy. Local resection was considered to be feasible because the resection line did not extend into the esophageal mucosa and the resection site could be less than half the circumference of the lumen. The submucosal tumor was resected completely and safely by LECS. The tumor was diagnosed as a gastric smooth muscle tumor finally. Nine months after surgery, a follow-up endoscopy showed reflux esophagitis. LECS was a useful technique for submucosal tumors of the cardiac region with hiatal hernia, but fundoplication might be considered for preventing backflow of gastric acid.
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Affiliation(s)
- Hajime Kashima
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JPN
| | - Satoru Kikuchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JPN
| | - Shinji Kuroda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JPN
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JPN
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19
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Carreras J, Kikuti YY, Miyaoka M, Hiraiwa S, Tomita S, Ikoma H, Kondo Y, Ito A, Nagase S, Miura H, Roncador G, Colomo L, Hamoudi R, Campo E, Nakamura N. Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant Diffuse Large B-Cell Lymphoma. Hematol Rep 2023; 15:188-200. [PMID: 36975733 PMCID: PMC10048669 DOI: 10.3390/hematolrep15010020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 03/01/2023] [Accepted: 03/09/2023] [Indexed: 03/16/2023] Open
Abstract
Diffuse large B-cell lymphoma with spindle cell morphology is a rare variant. We present the case of a 74-year-old male who initially presented with a right supraclavicular (lymph) node enlargement. Histological analysis showed a proliferation of spindle-shaped cells with narrow cytoplasms. An immunohistochemical panel was used to exclude other tumors, such as melanoma, carcinoma, and sarcoma. The lymphoma was characterized by a cell-of-origin subtype of germinal center B-cell-like (GCB) based on Hans’ classifier (CD10-negative, BCL6-positive, and MUM1-negative); EBER negativity, and the absence of BCL2, BCL6, and MYC rearrangements. Mutational profiling using a custom panel of 168 genes associated with aggressive B-cell lymphomas confirmed mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14. Based on the LymphGen 1.0 classification tool, this case had an ST2 subtype prediction. The immune microenvironment was characterized by moderate infiltration of M2-like tumor-associated macrophages (TMAs) with positivity of CD163, CSF1R, CD85A (LILRB3), and PD-L1; moderate PD-1 positive T cells, and low FOXP3 regulatory T lymphocytes (Tregs). Immunohistochemical expression of PTX3 and TNFRSF14 was absent. Interestingly, the lymphoma cells were positive for HLA-DP-DR, IL-10, and RGS1, which are markers associated with poor prognosis in DLBCL. The patient was treated with R-CHOP therapy, and achieved a metabolically complete response.
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Affiliation(s)
- Joaquim Carreras
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
- Correspondence: ; Tel.: +81-463-93-1121
| | - Yara Yukie Kikuti
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Masashi Miyaoka
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Shinichiro Hiraiwa
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Sakura Tomita
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Haruka Ikoma
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Yusuke Kondo
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Atsushi Ito
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Shunsuke Nagase
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Hisanobu Miura
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
| | - Giovanna Roncador
- Monoclonal Antibodies Unit, Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncologicas, CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
| | - Lluis Colomo
- Department of Pathology, Hospital del Mar, Passeig Maritim 25-29, 08003 Barcelona, Spain
| | - Rifat Hamoudi
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates
- Division of Surgery and Interventional Science, University College London, Gower Street, London WC1E 6BT, UK
| | - Elias Campo
- Department of Pathology, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Esther Koplowitz Center (CEK), Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), 08036 Barcelona, Spain
| | - Naoya Nakamura
- Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
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20
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Hornick JL, Webster F, Dei Tos AP, Hemmings C, Miettinen M, Oda Y, Raut CP, Rubin BP, Von Mehren M, Wardelmann E, Fletcher CDM. Dataset for reporting of gastrointestinal stromal tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2023; 82:376-384. [PMID: 36073677 DOI: 10.1111/his.14791] [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: 07/17/2022] [Revised: 09/04/2022] [Accepted: 09/05/2022] [Indexed: 01/20/2023]
Abstract
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and are among the most frequent sarcomas. Accurate diagnosis, classification, and reporting are critical for prognostication and patient management, including selection of appropriate targeted therapy. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of GIST. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major international pathology and cancer organizations. An international expert panel consisting of pathologists, a surgical oncologist, and a medical oncologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were subspecialized soft tissue tumour experts and affiliated with tertiary referral centres. Commentary was provided for each data item to explain its clinical relevance and the rationale for selection as a core or noncore element. Following international public consultation, the datasets, which include synoptic reporting guides, were finalized and ratified, and published on the ICCR website. These first international datasets for GIST are intended to promote high-quality, standardised pathology reporting. Their widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will ultimately help to improve the management of patients with GIST. All the ICCR datasets, including these on GIST, are freely available worldwide on the ICCR website (www.iccr-cancer.org/datasets).
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Affiliation(s)
- Jason L Hornick
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Fleur Webster
- International Collaboration on Cancer Reporting, Sydney, NSW, Australia
| | - Angelo Paolo Dei Tos
- Department of Pathology, Azienda Ospedaliera Universitaria di Padova, Padova, Italy.,Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | - Chris Hemmings
- Department of Anatomic Pathology, Canterbury Health Laboratories, Christchurch, New Zealand.,Department of Pathology and Biomedical Science, Christchurch Clinical School, University of Otago School of Medicine, Christchurch, New Zealand
| | - Markku Miettinen
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, Bethesda, MD, USA
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Chandrajit P Raut
- Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.,Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Brian P Rubin
- Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Margaret Von Mehren
- Department of Hematology and Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Eva Wardelmann
- Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany
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21
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Wu Y, Li W, Chen X, Wang H, Su S, Xu Y, Deng X, Yang T, Wei M, Li L, Liu Y, Yang J, Li W. DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis. Front Immunol 2023; 14:1051506. [PMID: 36776873 PMCID: PMC9909470 DOI: 10.3389/fimmu.2023.1051506] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/09/2023] [Indexed: 01/27/2023] Open
Abstract
Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis. The DOG1 expression profile was determined among TCGA samples and tissue microarrays. High levels of DOG1 expression were ubiquitously observed in multiple cancer samples from the alimentary tract determined by TCGA samples and tissue microarrays. Circulating tumor cells isolated from metastatic colon cancer patients were also positive for DOG1 expression. The mechanisms of anti-DOG1 antibody were investigated by dual-luciferase reporter assay. The anti-DOG1 antibody could inhibit proliferation and metastasis via p53 signaling in limited cancer cell lines. The anti-DOG1 antibody was conjugated with a microtubule inhibitor DM4, to construct a new anti-DOG1-DM4-ADC to strengthen its activity. The anti-DOG1-DM4-ADC showed cytotoxicity at the nanomolar level in vitro. In the murine xenograft tumor models, treatment of anti-DOG1-DM4-ADC achieved a significant tumor growth inhibition rate. Our study indicates that anti-DOG1-DM4-ADC may be promising therapeutic molecules for DOG1-positive alimentary tract tumors and may be effective in inhibiting recurrence after curative resection of liver metastases of colorectal origin.
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Affiliation(s)
- Yangping Wu
- Targeted Tracer Research and Development Laboratory, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wenting Li
- State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangzheng Chen
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Haichuan Wang
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Su
- Department of Chemistry, University of Illinois Chicago, Chicago, IL, United States
| | - Ying Xu
- Targeted Tracer Research and Development Laboratory, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangbing Deng
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Tinghan Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Mingtian Wei
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Li Li
- Institute of Clinical Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Yixin Liu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jinliang Yang
- State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China,*Correspondence: Weimin Li, ; Jinliang Yang,
| | - Weimin Li
- Targeted Tracer Research and Development Laboratory, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China,*Correspondence: Weimin Li, ; Jinliang Yang,
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22
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Muacevic A, Adler JR, Zeng J, Collins V, Zeizafoun N. A Rare Case of Breast Metastatic Gastrointestinal Stromal Tumor. Cureus 2023; 15:e34164. [PMID: 36843793 PMCID: PMC9949736 DOI: 10.7759/cureus.34164] [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] [Accepted: 01/22/2023] [Indexed: 01/25/2023] Open
Abstract
Gastrointestinal stromal tumor (GIST) is one of the most common spindle cell neoplasms of the alimentary system, and can arise anywhere along the gastrointestinal tract (GI). Its incidence rate is up to 22 cases per million, with a minor geographic variation. GIST is thought to originate from interstitial cell of Cajal, and its pathogenesis is related to molecular defects, such as KIT receptor tyrosine kinase or platelet-derived growth receptor alpha gene activation. While the majority of GISTs are known to show a benign disease course, metastases of high-grade forms to different organ systems have been seldom reported. We present a case with an unprecedented metastasis of GIST to the breast. The patient is a 62-year-old female with a history of the primary resection of GIST from the small intestine. Her disease course was initially complicated by multiple metastases, solely localized to the liver for which she had a living-donor liver transplant. The tumor harbored both KIT exon 11 and exon 17 mutation. Fourteen months post-transplant, the patient was found to have metastatic GIST on her breast biopsy. GIST metastasis to the breast is extremely rare. A consideration of this spindle cell neoplasm as a differential is recommended when clinical suspicion arises. The pathophysiology, current diagnostic tool, grading system, and treatment of this tumor are discussed.
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23
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Rottmann D, Abdulfatah E, Pantanowitz L. Molecular testing of soft tissue tumors. Diagn Cytopathol 2023; 51:12-25. [PMID: 35808975 PMCID: PMC10084007 DOI: 10.1002/dc.25013] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/27/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND The diagnosis of soft tissue tumors is challenging, especially when the evaluable material procured is limited. As a result, diagnostic ancillary testing is frequently needed. Moreover, there is a trend in soft tissue pathology toward increasing use of molecular results for tumor classification and prognostication. Hence, diagnosing newer tumor entities such as CIC-rearranged sarcoma explicitly requires molecular testing. Molecular testing can be accomplished by in situ hybridization, polymerase chain reaction, as well as next generation sequencing, and more recently such testing can even be accomplished leveraging an immunohistochemical proxy. CONCLUSION This review evaluates the role of different molecular tests in characterizing soft tissue tumors belonging to various cytomorphologic categories that have been sampled by small biopsy and cytologic techniques.
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Affiliation(s)
- Douglas Rottmann
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Eman Abdulfatah
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Liron Pantanowitz
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
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24
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Hu X, Zhang Q, Wang Z, Ren H, Su P, Kou Y. Retrospective study of the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumors in Chinese patients. Ann Diagn Pathol 2022; 61:152050. [DOI: 10.1016/j.anndiagpath.2022.152050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/17/2022] [Accepted: 10/03/2022] [Indexed: 11/01/2022]
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25
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Yang Y, Sun D, Tang K. Primary extragastrointestinal stromal tumors of the prostate: A case report and literature review. Front Oncol 2022; 12:1038853. [PMID: 36425555 PMCID: PMC9679634 DOI: 10.3389/fonc.2022.1038853] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/12/2022] [Indexed: 07/19/2024] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the main stromal tumors of the digestive tract. Extragastrointestinal stromal tumors (EGISTs) typically originate outside the gastrointestinal tract; are not associated with the stomach or intestinal walls; and are mainly derived from the mesentery, peritoneum, posterior peritoneum, bladder, and scrotum. However, EGISTs from the prostate are rare. Here, we present a case of EGIST that passed off in the prostate of a 62-year-old man. The patient undergoes transrectal guided trans-perineal prostate puncture, and pathological reports suggest a GIST. Tumor cells are spindle-shaped, and no obvious neoplastic necrosis is seen in the sections. Immunohistochemical results are robustly positive for CD117, DOG-1, and CD34 expression. The patient had a good prognosis after treatment with imatinib, no recurrence and no metastases after six months of follow-up, and the prognosis was good. This article also provides a literature review and discussion of the treatment of EGISTs.
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Affiliation(s)
- Yuxuan Yang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Second Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dengshun Sun
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kun Tang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Second Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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26
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Mathias-Machado MC, de Jesus VHF, de Carvalho Oliveira LJ, Neumann M, Peixoto RD. Current Molecular Profile of Gastrointestinal Stromal Tumors and Systemic Therapeutic Implications. Cancers (Basel) 2022; 14:5330. [PMID: 36358751 PMCID: PMC9656487 DOI: 10.3390/cancers14215330] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 07/25/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising from the intestinal pacemaker cells of Cajal. They compose a heterogenous group of tumors due to a variety of molecular alterations. The most common gain-of-function mutations in GISTs are either in the KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA) genes (10-15%), which are mutually exclusive. However, a smaller subset, lacking KIT and PDGFRA mutations, is considered wild-type GISTs and presents distinct molecular findings with the activation of different proliferative pathways, structural chromosomal and epigenetic changes, such as inactivation of the NF1 gene, mutations in the succinate dehydrogenase (SDH), BRAF, and RAS genes, and also NTRK fusions. Currently, a molecular evaluation of GISTs is imperative in many scenarios, aiding in treatment decisions from the (neo)adjuvant to the metastatic setting. Here, we review the most recent data on the molecular profile of GISTs and highlight therapeutic implications according to distinct GIST molecular subtypes.
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Affiliation(s)
| | | | | | - Marina Neumann
- Centro Paulista de Oncologia (Oncoclínicas), São Paulo 04538-132, Brazil
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27
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A Gastroenterologist's Approach to the Diagnosis and Management of Gastrointestinal Stromal Tumors. Gastroenterol Clin North Am 2022; 51:609-624. [PMID: 36153113 DOI: 10.1016/j.gtc.2022.06.009] [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] [Indexed: 02/21/2023]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. These tumors have been shown to harbor oncogenic mutations of the c-kit tyrosine kinase receptor or platelet-derived growth factor receptor alpha (PDGFRA). Immunohistochemical analysis of GISTs allows for the differentiation of these tumors from other mesenchymal tumors of the GI tract such as leiomyomas and leiomyosarcomas. All GISTs have the potential to behave in a malignant fashion. Tumor location, size, and mitotic index are factors used to predict the risk of malignant behavior. Endoscopy and endoscopic ultrasound play a critical role in the diagnosis of GISTs and can yield important information to further risk-stratify tumors and determine management. This article provides a gastroenterologist's perspective on the diagnosis and management of GISTs.
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28
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DOG1 as an Immunohistochemical Marker of Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis. Int J Mol Sci 2022; 23:ijms23179711. [PMID: 36077107 PMCID: PMC9456024 DOI: 10.3390/ijms23179711] [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: 08/03/2022] [Revised: 08/20/2022] [Accepted: 08/24/2022] [Indexed: 12/04/2022] Open
Abstract
DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43–0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.
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29
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Comparative Study on the Clinical Effects of Different Surgical Methods in the Treatment of Gastrointestinal Stromal Tumors. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1280756. [PMID: 35911134 PMCID: PMC9334061 DOI: 10.1155/2022/1280756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/23/2022] [Indexed: 11/18/2022]
Abstract
Objective The objective is to compare the clinical efficacy of laparoscopic resection (LAP), endoscopic full-thickness resection (EFR), and endoscopic submucosal dissection (ESD) in the treatment of gastrointestinal stromal tumors. Methods The clinical data of 105 patients who were treated in our hospital and diagnosed with GIST by pathology after surgery from March 2019 to March 2021 were collected. Patients were divided into the LAP group, EFR group, and ESD group according to different surgical methods. The clinical data, surgical conditions, complications, and postoperative conditions of the patients were recorded retrospectively. Patients were followed up closely after surgery. Results The operation time of the EFR group and ESD group was shorter than that of the LAP group, and the operation time of the EFR group was shorter than that of the ESD group (P < 0.05). The amount of intraoperative blood loss in the EFR group and ESD group was lower than that in the LAP group (P < 0.05). There was no significant difference in the complete resection rate among the three groups (P > 0.05). There was no significant difference in the total incidence of complications among the three groups (P > 0.05). The postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs of the EFR group and ESD group were lower than those of the LAP group (P < 0.05). No recurrence or metastasis cases were found in the three groups during the follow-up period, and there were no GIST-related deaths in the three groups. Conclusion LAP, EFR, and ESD have good curative effect, good safety, and good prognosis in the treatment of GIST. But compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization cost.
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30
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Cao Y, Zhang X, Chen Q, Rao X, Qiu E, Wu G, Lin Y, Zeng Z, Zheng B, Li Z, Cai Z, Wang H, Han S. Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report. Front Oncol 2022; 12:920762. [PMID: 35982969 PMCID: PMC9378866 DOI: 10.3389/fonc.2022.920762] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 05/04/2022] [Indexed: 11/24/2022] Open
Abstract
The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-derived organoids (PDOs) are potential 3D in vitro models of tissues that can be used to identify sensitivity toward specific targets in patients with tumors and allow for personalized medicine when drugs specific for newly identified genetic locus mutations are not yet available. This study describes a 68-year-old patient who complained of diffused abdominal pain and intermittent melena lasting more than 10 days. He has no other gastrointestinal abnormalities, prior abdominal surgery, or related family history. Surgery was conducted first to remove the lesions and ascertain the disease through histology and immunohistochemical stains of the mass. Immunohistochemistry revealed that the tumor was positive for CD117 and Dog-1. Based on the above findings, he was diagnosed with GISTs. Gene detection analysis and organoid culture were then performed to verify clinical decisions. KIT p.V560E and the reduced number of RB1 copies were identified as two obvious mutations, so the patient was administrated first-line treatment of imatinib 400 mg/d. However, progressive disease prompted us to switch to sunitinib, and his condition gradually improved. Meanwhile, organoid culture showed sensitivity to sunitinib and tolerance to imatinib with half-maximal inhibitory concentration (IC50) values of 0.89 and >20, respectively. In summary, to the best of our knowledge, this is the first time that the established organoid culture indicated that the GISTs organoid could identify the sensitivity to target therapies and facilitate individual-based treatment.
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Affiliation(s)
- Ying Cao
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xi Zhang
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Qianyun Chen
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Xi Rao
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Enming Qiu
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Gang Wu
- Department of Oncology, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Yu Lin
- Department of Pathology, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Ziqi Zeng
- Department of Pathology, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Bin Zheng
- Guangdong Research Center of Organoid Engineering and Technology, Accurate International Biotechnology Company, Guangzhou, China
| | - Zhou Li
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Zhai Cai
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuai Han
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, The Second Affiliated Hospital of Southern Medical University, Guangzhou, China
- *Correspondence: Shuai Han,
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31
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Wong SJ, Wang HP, Shun CT, Chen CC, Han ML, Chen JH, Huang CT, Cheng TY. Tissue diagnosis necessary for small endoscopic ultrasound-suspected gastric gastrointestinal stromal tumors 2 cm or less in size: A prospective study focusing on the endoscopic incisional biopsy. J Gastroenterol Hepatol 2022; 37:1588-1595. [PMID: 35502128 DOI: 10.1111/jgh.15876] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/05/2022] [Accepted: 04/22/2022] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM The small endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs), gastric subepithelial tumors at the muscularis propria layer on EUS, are detected frequently. Bite-on-bite forceps biopsy and EUS-guided tissue sampling yield variable results. This study aimed to analyze clinicopathologic features of the small EUS-suspected gastric GISTs 2 cm or less in size and to evaluate the efficacy and safety of the endoscopic incisional biopsy (EIB) for these small tumors. METHODS This prospective study investigated 70 patients with small EUS-suspected gastric GISTs 2 cm or less in size in two stages. Firstly, 30 patients were recruited for the efficacy and safety evaluation of the EIB. Secondly, 40 patients were randomly assigned to receive either EIB or the bite-on-bite biopsy for comparison of the diagnostic yield, procedure time, and adverse event rate. RESULTS Combining two study stages, leiomyoma (74%) was diagnosed histologically to outnumber GIST (26%) with a diagnostic rate of 94% for patients receiving EIB. KIT exon 11 mutations (50%) and PDGFRA exon 12 mutations (16%) were detected in the small gastric GISTs. In the direct comparison, the diagnostic yield of EIB and the bite-on-bite biopsy was 85% and 50%, respectively (P = 0.018). There was no statistically significant difference of the mean procedure time or adverse event rate between these two groups. CONCLUSIONS Leiomyoma is more common than expected among these small tumors. Tissue diagnosis with an effective and safe sampling technique, such as EIB, is necessary for making further clinical decisions.
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Affiliation(s)
- Shenq-Jie Wong
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, Taiwan
| | - Hsiu-Po Wang
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Chuan Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Lun Han
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jiann-Hwa Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu-Chi Hospital, New Taipei City, Taiwan
| | - Chung-Tsui Huang
- Division of Gastroenterology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Tsu-Yao Cheng
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Laboratory Medicine, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan
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32
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Khan J, Ullah A, Waheed A, Karki NR, Adhikari N, Vemavarapu L, Belakhlef S, Bendjemil SM, Mehdizadeh Seraj S, Sidhwa F, Ghleilib I, Foroutan S, Blakely AM, Del Rivero J, Karim NA, Vail E, Heneidi S, Mesa H. Gastrointestinal Stromal Tumors (GIST): A Population-Based Study Using the SEER Database, including Management and Recent Advances in Targeted Therapy. Cancers (Basel) 2022; 14:3689. [PMID: 35954353 PMCID: PMC9367571 DOI: 10.3390/cancers14153689] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 07/23/2022] [Accepted: 07/26/2022] [Indexed: 02/04/2023] Open
Abstract
Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm. Molecular genetic advances, current management guidelines, and advances in targeted therapy are discussed. Methods: Demographic and clinical data from GIST patients were retrieved from the SEER research plus database for the period 2000−2018. Statistical analysis was performed with IBM SPSS® v20.2 software using the Chi-square test, paired t-test, multivariate analysis, and Kaplan−Meier functions. Results: A total of 10,833 patients with GIST were identified. Most patients were between 60−74 years of age: 40%, Caucasian: 68%, and the male to female ratio was 1.1:1. The most common primary tumor sites were stomach: 63%, small intestine: 30%, rectum: 3%, and esophagus: 0.7%. When reported, the grade of differentiation was well: 38%, moderately: 32%, undifferentiated: 19%, poorly: 12%. The size of most tumors ranged between 6−10 cm: 36% and they were treated by surgical intervention: 82% and/or chemotherapy/targeted therapy: 39%. The stage was localized: 66%, advanced: 19%, and regional: 15%. The 5-year survival was 74% (95% confidence interval (95% CI) = 72.6−74.7), and the 5-year cause-specific survival 82% (95% CI = 80.7−82.6). The 5-year cause-specific survival by treatment included surgery at 86% (95% CI = 85.4−87.3), chemotherapy/targeted therapy with or without surgery at 77% (95% CI = 75.7−78.9), and radiation at 75% (95% CI = 74.5−80). On multivariable analysis tumor size > 5 cm, poorly and undifferentiated grade, age > 60, and distant metastases at presentation were associated with worse overall survival. Conclusion: GISTs comprise 1−2% of malignancies of the GI tract, usually affect male Caucasians between the ages of 60 and 74 years, most tumors occur in the stomach and small intestine, and are usually >5 cm, but still localized, at the time of diagnosis. Most tumors receive multimodality surgical and chemotherapy/targeted therapy treatment, with a 5-year overall survival of 74% and cause-specific survival of 82%. GIST patients would benefit from enrollment in large clinical trials to establish better therapy guidelines for unresectable, treatment-refractory, and recurrent tumors.
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Affiliation(s)
- Jaffar Khan
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Asad Ullah
- Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
| | - Abdul Waheed
- Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA; (A.W.); (S.M.B.); (S.M.S.); (F.S.); (S.F.)
| | - Nabin Raj Karki
- Georgia Cancer Center, Department of Hematology Oncology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA;
| | - Nawaraj Adhikari
- Department of Medicine, Bon Secours Memorial Regional Medical Center, Mechanicsville, VA 23116, USA;
| | - Lakshmi Vemavarapu
- Department of Pathology, Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, USA;
| | - Sami Belakhlef
- Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; (S.B.); (I.G.)
| | - Samy Malik Bendjemil
- Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA; (A.W.); (S.M.B.); (S.M.S.); (F.S.); (S.F.)
| | - Siamak Mehdizadeh Seraj
- Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA; (A.W.); (S.M.B.); (S.M.S.); (F.S.); (S.F.)
| | - Feroze Sidhwa
- Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA; (A.W.); (S.M.B.); (S.M.S.); (F.S.); (S.F.)
| | - Intisar Ghleilib
- Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; (S.B.); (I.G.)
| | - Shahin Foroutan
- Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA; (A.W.); (S.M.B.); (S.M.S.); (F.S.); (S.F.)
| | - Andrew M. Blakely
- National Cancer Institute (NCI), Bethesda, MD 20892, USA; (A.M.B.); (J.D.R.)
| | - Jaydira Del Rivero
- National Cancer Institute (NCI), Bethesda, MD 20892, USA; (A.M.B.); (J.D.R.)
| | - Nagla Abdel Karim
- Inova Schar Cancer Institute, Department of Medicine, University of Virginia, Fairfax, VA 22031, USA;
| | - Eric Vail
- Molecular Pathology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (E.V.); (S.H.)
| | - Saleh Heneidi
- Molecular Pathology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; (E.V.); (S.H.)
| | - Hector Mesa
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
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Salmikangas S, Böhling T, Merikoski N, Jagdeo J, Sampo M, Vesterinen T, Sihto H. Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors. Cancers (Basel) 2022; 14:3212. [PMID: 35804982 PMCID: PMC9265085 DOI: 10.3390/cancers14133212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 12/10/2022] Open
Abstract
GIST is a rare soft tissue sarcoma, for which KIT and DOG1 are used as highly sensitive diagnostic markers. Other diagnostic markers include CD34, protein kinase C θ, deficiency of succinate dehydrogenase complex subunit B, carbonic anhydrase II, and type I insulin-like growth factor receptor. We investigated the role of TNS2 as a diagnostic biomarker by using immunohistochemistry in 176 GISTs and 521 other sarcomas. All GISTs expressed TNS2, with intermediate or high expression in 71.4% of samples. The majority (89.8%) of other sarcomas were negative for TNS2, and intermediate to strong staining was only seen in 2.9% of samples. Strong TNS2 staining was associated with gastric location (gastric 52.8% vs. non-gastric 7.2%; p < 0.001), absence of metastases (non-metastatic tumors 44.3% vs. metastatic tumors 5.9%; p = 0.004), female sex (female 45.9% vs. male 33.8%; p = 0.029), and tumors of lower risk categories (very low or low 46.9% vs. intermediate 51.7% vs. high 29.0%; p = 0.020). TNS2 expression did not correlate with overall survival or metastasis-free survival. No associations between TNS2 expression and KIT/PDGFRA mutation status, tumor size, mitotic count, or age of the patient were detected. The results provide conclusive evidence for the value of TNS2 as a sensitive and specific diagnostic biomarker for GIST.
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Affiliation(s)
- Sami Salmikangas
- Department of Pathology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland; (T.B.); (N.M.); (J.J.); (H.S.)
| | - Tom Böhling
- Department of Pathology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland; (T.B.); (N.M.); (J.J.); (H.S.)
| | - Nanna Merikoski
- Department of Pathology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland; (T.B.); (N.M.); (J.J.); (H.S.)
| | - Joanna Jagdeo
- Department of Pathology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland; (T.B.); (N.M.); (J.J.); (H.S.)
| | - Mika Sampo
- Department of Pathology, HUSLAB, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland; (M.S.); (T.V.)
| | - Tiina Vesterinen
- Department of Pathology, HUSLAB, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland; (M.S.); (T.V.)
| | - Harri Sihto
- Department of Pathology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland; (T.B.); (N.M.); (J.J.); (H.S.)
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Koufopoulos N, Damaskou V, Siozopoulou V, Kokoropoulos P, Gouloumis AR, Arkadopoulos N, Panayiotides IG. DOG1-Positive Primary Mesenteric Leiomyosarcoma: Report of a Case and Review of the Literature. Cureus 2022; 14:e25263. [PMID: 35755504 PMCID: PMC9224980 DOI: 10.7759/cureus.25263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2022] [Indexed: 11/20/2022] Open
Abstract
The mesentery constitutes a common location for the metastatic spread of malignant gastrointestinal tumors. Primary mesenteric tumors, on the other hand, are very rare; lymphomas are the most common, followed by benign and malignant mesenchymal tumors. We present a case of a 43-year-old patient operated on for a primary mesenteric leiomyosarcoma with a positive immunostain for DOG1, despite having no KIT or PDGFRa mutations on molecular analysis. Moreover, we review the pertinent literature.
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Karthikeyan M, Kolandasamy C, Naganath Babu OL. Malignant Gastrointestinal Stromal Tumor of Rectum: A Case Report and Review of Literature. Surg J (N Y) 2022; 8:e60-e64. [PMID: 35187230 PMCID: PMC8850004 DOI: 10.1055/s-0042-1742778] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 12/22/2021] [Indexed: 11/07/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract accounting for less than 1% of all gut tumors. GISTs occurring in the rectum are extremely rare and these usually present at an advanced stage compared with other sites. We report a case of a middle-aged female who presented with features of anemia and subacute obstruction due to a large rectal tumor and underwent abdominoperineal resection. The histopathological examination confirmed the diagnosis of high-grade malignant GIST with multiple lymph nodal metastasis. She was started on adjuvant imatinib therapy and is on follow-up without any evidence of recurrence. The authors conclude that GIST must be included in the differential diagnosis of a rectal tumor. Diagnosis is established by biopsy and immunohistochemistry studies. Surgical resection with histological negative margins is the standard curative treatment. Adjuvant targeted therapy can reduce long-term recurrence in high-risk cases.
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Affiliation(s)
- Mohan Karthikeyan
- Institute of Surgical Gastroenterology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
| | - Chinnusamy Kolandasamy
- Institute of Surgical Gastroenterology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
| | - Obla L Naganath Babu
- Institute of Surgical Gastroenterology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
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Dermawan JK, Zhang L, Singer S, Chi P, Antonescu CR. Low-grade endometrial stromal sarcoma-like tumors in male with JAZF1 gene fusions. Genes Chromosomes Cancer 2022; 61:63-70. [PMID: 34651371 PMCID: PMC8811592 DOI: 10.1002/gcc.23003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 10/05/2021] [Indexed: 02/03/2023] Open
Abstract
Low-grade endometrial stromal sarcoma (ESS) is a hormone-responsive low-grade sarcoma typically occurring in the uterine corpus in women. Their genetic hallmarks are recurrent gene fusions involving JAZF1, partnering with either SUZ12 gene or less commonly with PHF1. Low-grade ESS-like sarcoma, or endometrioid stromal sarcoma, is exceptionally rare in males and has been reported to date only in two cases, one in the paratesticular area and the other of prostatic stromal origin. We report herein two new cases of low-grade ESS-like sarcoma in male patients, one presenting as a periprostatic/peri-rectal mass with a JAZF1-GLI3 fusion, while the other as a paratesticular mass with a JAZF1-PHF1 fusion. As the GLI3 fusion appeared novel, we searched the transcriptional signature of 35 low-grade ESS from our archives and found a similar JAZF1-GLI3 fusion in a low-grade ESS arising from the uterine corpus, supporting a common pathogenesis. Histopathologically, both cases demonstrate cellular, monotonous proliferation of ovoid to fusiform cells with a background of arteriolar vascular network. Immunohistochemically, the neoplastic cells express ER, PR, and CD10, similar to ESS. One case also expresses diffuse and strong AR. On follow-up, the patient with the periprostatic mass recurred 2 years after initial surgery with peritoneal "sarcomatosis." We describe the salient diagnostic morphologic, immunohistochemical, and molecular features and discuss the differential diagnosis and possible pathogenesis of this unusual entity.
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Affiliation(s)
| | - Lei Zhang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Samuel Singer
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ping Chi
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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Agaimy A. [Mesenchymal tumors and tumor-like lesions of the gastrointestinal tract: an overview]. DER PATHOLOGE 2022; 43:31-44. [PMID: 34919183 DOI: 10.1007/s00292-021-01040-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/15/2021] [Indexed: 06/14/2023]
Abstract
Mesenchymal tumors and tumor-like lesions of the gastrointestinal (GI) tract are uncommon. They vary from reactive tumefactive lesions and benign neoplasms to highly aggressive sarcomas. Among them, GI stromal tumors (GISTs) are most common, followed, with less frequency, by smooth muscle and neurogenic tumors. The major challenge resides in correctly identifying GISTs and providing a comprehensive report (including risk assessment and genotyping) that represents the basis for an optimized surgical-oncological treatment and/or adjuvant therapy. On the other hand, the challenge of benign lesions is to find a good name (well understandable and reproducible diagnostic term) that helps avoid diagnostic ambiguity and prognostic uncertainty so that overprognostication and overtreatment can be prevented. Moreover, several recently described genetically defined benign and malignant entities need be correctly diagnosed due to their special "targeted" therapeutic options and to further characterize their clinicopathological and biological properties in the future. These recent entities include aggressive epithelioid inflammatory myofibroblastic sarcoma (ALK-RANBP2-driven), malignant gastrointestinal neuroectodermal tumor (EWSR1-ATF1/CREB-related), NTRK-rearranged neoplasms, and, most recently, colorectal NUTM1-rearranged sarcomas. This review highlights the major clinicopathological features of gastrointestinal mesenchymal lesions in light of recent developments.
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Affiliation(s)
- Abbas Agaimy
- Pathologisches Institut, Universitätsklinikum Erlangen, Krankenhausstraße 8-10, 91054, Erlangen, Deutschland.
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Immunohistochemical features of gastrointestinal stromal tumors and their role for differential diagnosis and prognosis. EUREKA: HEALTH SCIENCES 2021. [DOI: 10.21303/2504-5679.2021.002183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The aim. To clarify all most important immunohistochemical features of gastrointestinal stromal tumors with different histological patterns and analyze the role of expression of Ki-67, MMP-9, VEGF and p16ink4A as a predictive markers of tumor progression.
Materials and methods. The study is based on analysis of 100 primary GISTs for description of their morphological features and 36 GISTs taken from this 100 for study of prognostic markers.
Results. All spindle cell GISTs have shown diffuse expression of CD117 in tumor cells. The levels of CD117 expression varied from strong expression (3+) until mild expression (1+). Strong expression were seen in 75,8 % of spindle cell GISTs. Epithelioid GISTs demonstrated heterognous moderate or mild expression of CD117. All primary epithelioid GISTs from patients that had relapse of tumor in period from 1 till 3 years demonstrated focal mild expression of CD 117 in tumor cells. Expression of DOG-1 were seen in all 100 cases of GISTs, that were included in our study. The strong expression of DOG-1 (3+) were seen in all 45 GISTs that had low mitotic rate (≤5 mitoses per 50HPF) and not associated with their histological pattern. GISTs with high mitotic rate demonstrated heterogeneous expression of DOG-1 in tumors: moderate expression (2+) with patchy areas of strong expression (3+). Expression of CD56 was not found in spindle cell GISTs, but single tumor cells of epithelioid GISTs that had high mitotic rate demonstrated expression of this marker. The average expression of p16ink4A were higher in tumors that gave relapses compared with tumors without relapses (50,3 % versus 5,7 % respectively, U-test=16.5; p≤0,01).The average expression of MMP-9 also were significantly higher in GISTs that gave relapses: 63,2 % compared with 13,4 % in GISTs without relapse (U-test=16; p≤0 ,01).The strong VEGF expression was found in 66,7 % of GISTs that had relapses and only in 8,3 % of GISTs without relapses. 50 % of GISTs without relapses was negative for VEGF. Finally, the average expression of Ki-67 were 13,4 % in GISTs with relapses and 8,7 % in GISTs without them (U-test=16; p≤0,01).
Conclusion. We highly recommend using DOG-1 for epithelioid GISTs. Additionally in epithelioid GISTs can be used CD56 that can give focal positive reaction in some tumour cells. The following minimal panel of markers for differential diagnosis of spindled GISTs from other mesenchymal tumors of gastrointestinal tract is proposed: CD117, DOG-1 and SMA, where the first too markers will demonstrated the moderate or strong diffuse expression and SMA can be occasionally positive in some tumor cells. p16ink4A, ki-67, VEGF and MMP-9 can be used as additional prognostic markers in GISTs.
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Otsuka Y, Bai X, Tanaka Y, Ihara E, Chinen T, Ogino H, Ogawa Y. Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter. Eur J Pharmacol 2021; 910:174491. [PMID: 34506779 DOI: 10.1016/j.ejphar.2021.174491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 08/27/2021] [Accepted: 09/03/2021] [Indexed: 11/15/2022]
Abstract
The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. DMPP-induced relaxation was abolished by not only 1 μM tetrodotoxin but also the inhibition of ICC activity by pretreatment with 100 μM carbenoxolone (a gap junction inhibitor), pretreatment with 100 μM CaCCinh-A01 (an anoctamin-1 blocker acting as a calcium-activated chloride channel inhibitor), and pretreatment with Cl--free solution. However, pretreatment with 100 μM Nω-nitro-L-arginine methyl ester had little effect on DMPP-induced relaxation. Furthermore, DMPP-induced relaxation was inhibited by pretreatment with 1 mM suramin, a purinergic P2 receptor antagonist, but not by 1 μM VIP (6-28), a vasoactive intestinal peptide (VIP) receptor antagonist. Stimulation of the purinergic P2 receptor with adenosine triphosphate (ATP) induced relaxation, which was abolished by the inhibition of ICC activity by pretreatment with CaCCinh-A01. In conclusion, membrane hyperpolarization of the ICCs via the activation of anoctamin-1 plays a central role in DMPP-induced relaxation. ATP may be a neurotransmitter for inhibitory enteric neurons, which stimulate the ICCs. The ICCs act as the interface of neurotransmission of nicotinic acetylcholine receptor in order to induce LES relaxation.
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Affiliation(s)
- Yoshihiro Otsuka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Xiaopeng Bai
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshimasa Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Takatoshi Chinen
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Haruei Ogino
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Jansen K, Farahi N, Büscheck F, Lennartz M, Luebke AM, Burandt E, Menz A, Kluth M, Hube-Magg C, Hinsch A, Höflmayer D, Weidemann S, Fraune C, Möller K, Lebok P, Sauter G, Simon R, Uhlig R, Wilczak W, Jacobsen F, Minner S, Krech R, Clauditz T, Bernreuther C, Dum D, Krech T, Marx A, Steurer S. DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples. Pathol Res Pract 2021; 228:153663. [PMID: 34717148 DOI: 10.1016/j.prp.2021.153663] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 10/17/2021] [Indexed: 02/03/2023]
Abstract
DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n = 1002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p < 0.0001) and absence of HPV infection in squamous cell carcinomas (p = 0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.
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Affiliation(s)
- Kristina Jansen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nagina Farahi
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas M Luebke
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sören Weidemann
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rainer Krech
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Till Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Andreas Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Sivasubramaniam P, Tiegs-Heiden CA, Sturgis CD, Hagen CE, Hartley CP, Thangaiah JJ. Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls. Ann Diagn Pathol 2021; 55:151813. [PMID: 34509898 DOI: 10.1016/j.anndiagpath.2021.151813] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 08/25/2021] [Indexed: 12/28/2022]
Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement.
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Affiliation(s)
| | | | - Charles D Sturgis
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Catherine E Hagen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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42
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Tossamartvorakul M, Mendoza MCVR, Huang KG, Chang SH. Metastatic Smooth Muscle Tumor of Uncertain Malignant Potential after Laparoscopic Presuming Myomectomy. Gynecol Minim Invasive Ther 2021; 10:187-190. [PMID: 34485068 PMCID: PMC8384015 DOI: 10.4103/gmit.gmit_44_20] [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: 05/18/2020] [Revised: 06/09/2020] [Accepted: 08/25/2020] [Indexed: 12/25/2022] Open
Abstract
A 38-year-old para-2 female underwent laparoscopic myomectomy with uncontained morcellation. Three years later, she complained of epigastric pain. An intraperitoneal 3 cm mass beneath the umbilicus was showed on computed tomography (CT) scan. With the impression of gastrointestinal stromal tumor, she underwent open laparotomy at the general surgery department. A tumor was excised. Pathological examination showed that the tumor was consistent with a smooth muscle tumor of uncertain malignant potential smooth muscle tumors of uncertain malignant (STUMP). Six years postlaparoscopic myomectomy, during a regular follow-up, three parauterine masses were found on ultrasonography and CT scan. She underwent laparoscopic surgery for hysterectomy, bilateral salpingectomy, and excision of the masses. The masses were again diagnosed as STUMP. This case presents a recurrence of a rare type of smooth muscle tumor after uncontained morcellation. If myomas are to be removed with morcellation, it should only be used appropriately with a compatible containment system, and the risk of occult malignancy should be counseled.
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Affiliation(s)
- Marisa Tossamartvorakul
- Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration General Hospital, Bangkok, Thailand.,Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
| | - Marie Christine Valerie R Mendoza
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.,Department of Obstetrics and Gynecology, University of the Philippines Manila, Philippine General Hospital, Manila, Philippines, Asia
| | - Kuan-Gen Huang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
| | - Shu-Han Chang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
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Jansen K, Büscheck F, Moeller K, Kluth M, Hube-Magg C, Blessin NC, Perez D, Izbicki J, Neipp M, Mofid H, Daniels T, Nahrstedt U, Fraune C, Jacobsen F, Bernreuther C, Lebok P, Sauter G, Uhlig R, Wilczak W, Simon R, Steurer S, Burandt E, Marx A, Krech T, Clauditz T. DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness. PeerJ 2021; 9:e11905. [PMID: 34414034 PMCID: PMC8344676 DOI: 10.7717/peerj.11905] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/13/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. METHODS DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. RESULTS DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.
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Affiliation(s)
- Kristina Jansen
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | | | - Martina Kluth
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | | | - Daniel Perez
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jakob Izbicki
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | | | | | | | | | - Frank Jacobsen
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Patrick Lebok
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ria Uhlig
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Ronald Simon
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas Marx
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Academic Hospital Fuerth, Fuerth, Germany
| | - Till Krech
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrück, Germany
| | - Till Clauditz
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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44
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Feng L, Luo J, Yi F. Expression of DOG1 in peripheral blood cells of patients with gastrointestinal stromal tumor. Arab J Gastroenterol 2021; 22:99-103. [PMID: 34088624 DOI: 10.1016/j.ajg.2021.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 03/02/2021] [Accepted: 03/29/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND AND STUDY AIMS The diagnosis and surveillance of gastrointestinal stromal tumor (GIST) rely on pathology and immunochemistry (IHC), making it complicated and invasive. Noninvasive and convenient biomarkers of this disease need to be explored. The high specificity and sensitivity of IHC in detecting GIST 1 (DOG1) in biopsy indicate that it is also expressed in circulating tumor cells of the blood and may be an ideal biomarker for GIST. This aimed to detect the expression of DOG1 in peripheral blood cells (PBCs) and determine the relationship between DOG1 expression and clinical factors. PATIENTS AND METHODS A total of 45 patients with GIST and 46 healthy controls (HCs) were recruited from the Second Affiliated Hospital of Nanchang University between December 2015 and June 2018. PBCs were isolated from peripheral venous blood by density gradient centrifugation. RNA was extracted from PBCs, and DOG1 mRNA was detected by quantitative reverse transcription polymerase chain reaction. DOG1 mRNA expression between GIST and HC was compared, and the relationship between clinical factors and DOG1 was also analyzed. RESULTS DOG1 mRNA expression in PBCs was significantly higher in patients with GIST than that in HCs (3.326 [1.942-5.328] versus 0.744 [0.269-1.087], p < 0.01). The specificity and sensitivity were 88.9% and 89.1%, respectively (AUC = 0.912). Tumor diameter and risk of aggressive behavior were correlated with DOG1 expression, and other clinical factors (sex, age, location, number of phase-splitting cells, Ki-67 index, metastatic status) did not show any relationship with DOG1 expression. However, clinical factors, including tumor diameter and risk grade, were not independent factors in DOG1 expression when multivariate analysis was conducted. CONCLUSION DOG1 expressions were significantly higher in patients with GIST than that in HCs. Tumor diameter and risk classification correlated with DOG1 expression but were not independent factors. DOG1 in PBCs is a promising noninvasive biomarker for GIST.
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Affiliation(s)
- Long Feng
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China; Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 330006, PR China
| | - Jinfeng Luo
- Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 330006, PR China; Department of Oncology, Meizhou People's Hospital, Meizhou 514031, PR China
| | - Fengming Yi
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China; Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 330006, PR China.
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Sbaraglia M, Businello G, Bellan E, Fassan M, Dei Tos AP. Mesenchymal tumours of the gastrointestinal tract. Pathologica 2021; 113:230-251. [PMID: 34294940 PMCID: PMC8299319 DOI: 10.32074/1591-951x-309] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal tumours represent a heterogenous group of neoplasms encopassing benign, intermediate malignancy, and malignant entities. Sarcomas account for approximately 1% of human malignancies. In consideration of their rarity as well as of intrinsic complexity, diagnostic accuracy represents a major challenge. Traditionally, mesenchymal tumours are regarded as lesions the occurrence of which is mostly limited to somatic soft tissues. However, the occurrence of soft tissue tumours at visceral sites represent a well recognized event, and the GI-tract ranks among the most frequently involved visceral location. There exist entities such as gastrointestinal stromal tumours (GIST) and malignant gastointestinal neuroectodermal tumors that exhibit exquisite tropism for the GI-tract. This review will focus also on other relevant clinico-pathologic entities in which occurrence at visceral location is not at all negligible.
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Affiliation(s)
- Marta Sbaraglia
- Department of Pathology, Azienda Ospedale-Università Padova, Padua, Italy.,Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | - Gianluca Businello
- Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | - Elena Bellan
- Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | - Matteo Fassan
- Department of Pathology, Azienda Ospedale-Università Padova, Padua, Italy.,Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | - Angelo Paolo Dei Tos
- Department of Pathology, Azienda Ospedale-Università Padova, Padua, Italy.,Department of Medicine, University of Padua School of Medicine, Padua, Italy
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Lim J, Baeg MK, Ahn S, Ha MH, Ko SH, Kwon H, Han J. C-kit-negative Extragastrointestinal Stromal Tumor Originating in the Mesentery Misdiagnosed as an Ovarian Tumor before Surgery. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2020.0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Al-Share B, Alloghbi A, Al Hallak MN, Uddin H, Azmi A, Mohammad RM, Kim SH, Shields AF, Philip PA. Gastrointestinal stromal tumor: a review of current and emerging therapies. Cancer Metastasis Rev 2021; 40:625-641. [PMID: 33876372 DOI: 10.1007/s10555-021-09961-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/29/2021] [Indexed: 02/07/2023]
Abstract
Gastrointestinal stromal tumors (GIST) are rare neoplasms arising from the interstitial cell of Cajal in the gastrointestinal tract. Two thirds of GIST in adult patients have c-Kit mutation and smaller fractions have platelet derived growth factor receptor alpha (PDGFRA) mutation. Surgery is the only curative treatment for localized disease. Imatinib improves survival when used adjuvantly and in advanced disease. Several targeted therapies have also improved survival in GIST patients after progression on imatinib including sunitinib and regorafenib. Recently, United States Federal and Drug Administration (FDA) approved two new tyrosine kinase inhibitors for the treatment of heavily pretreated advanced/unresectable GIST including avapritinib (a selective inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib (a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this article, we will provide a comprehensive review of GIST including the current standard of care treatment and exploring future paradigm shifts in therapy.
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Affiliation(s)
- Bayan Al-Share
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Abdulrahman Alloghbi
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Mohammed Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Hafiz Uddin
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Asfar Azmi
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Ramzi M Mohammad
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Steve H Kim
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Anthony F Shields
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Philip A Philip
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA.
- Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI, USA.
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Diagnostic Immunohistochemistry of Soft Tissue and Bone Tumors: An Update on Biomarkers That Correlate with Molecular Alterations. Diagnostics (Basel) 2021; 11:diagnostics11040690. [PMID: 33921435 PMCID: PMC8069362 DOI: 10.3390/diagnostics11040690] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 03/31/2021] [Accepted: 04/01/2021] [Indexed: 02/06/2023] Open
Abstract
The diagnosis of benign and malignant soft tissue and bone neoplasms is a challenging area of surgical pathology, due to the large number, rarity, and histologic diversity of tumor types. In recent years, diagnosis and classification has been aided substantially by our growing understanding of recurrent molecular alterations in these neoplasms. Concurrently, the role of diagnostic immunohistochemistry has also expanded, with the development of numerous biomarkers based on underlying molecular events. Such biomarkers allow us to infer the presence of these events and can therefore substitute for other ancillary molecular genetic techniques (e.g., fluorescence in situ hybridization, polymerase chain reaction, and next-generation sequencing). In this review, we discuss a range of biomarkers currently available for these neoplasms, highlighting the accuracy, staining characteristics, and interpretation pitfalls of each antibody. These include immunohistochemical antibodies that represent reliable surrogates for the detection of gene fusions (e.g., STAT6, CAMTA1, FOSB, DDIT3) and more recently described breakpoint-specific antibodies (e.g., SS18-SSX, PAX3/7-FOXO1). Additionally, discussed are markers that correlate with the presence of gene amplifications (e.g., MDM2, CDK4), deletions (e.g., SMARCB1, SMARCA4), single nucleotide variants (e.g., G34W, K36M), aberrant methylation (H3K27me3), and increased expression as discovered through gene expression profiling (e.g., MUC4, DOG1, ETV4, NKX2.2, NKX3.1).
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Abstract
Gastrointestinal stromal tumours (GIST) have an incidence of ~1.2 per 105 individuals per year in most countries. Around 80% of GIST have varying molecular changes, predominantly mutually exclusive activating KIT or PDGFRA mutations, but other, rare subtypes also exist. Localized GIST are curable, and surgery is their standard treatment. Risk factors for relapse are tumour size, mitotic index, non-gastric site and tumour rupture. Patients with GIST with KIT or PDGFRA mutations sensitive to the tyrosine kinase inhibitor (TKI) imatinib that are at high risk of relapse have improved survival with adjuvant imatinib treatment. In advanced disease, median overall survival has improved from 18 months to >70 months since the introduction of TKIs. The role of surgery in the advanced setting remains unclear. Resistance to TKIs arise mainly from subclonal selection of cells with resistance mutations in KIT or PDGFRA when they are the primary drivers. Advanced resistant GIST respond to second-line sunitinib and third-line regorafenib, as well as to the new broad-spectrum TKI ripretinib. Rare molecular forms of GIST with alterations involving NF1, SDH genes, BRAF or NTRK genes generally show primary resistance to standard TKIs, but some respond to specific inhibitors of the activated genes. Despite major advances, many questions in both advanced and localized disease remain unanswered.
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Affiliation(s)
- Jean-Yves Blay
- Department of Medicine, Centre Leon Berard, UNICANCER & University Lyon I, Lyon, France.
| | - Yoon-Koo Kang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Toshiroo Nishida
- Surgery Department, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
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Brčić I, Argyropoulos A, Liegl-Atzwanger B. Update on Molecular Genetics of Gastrointestinal Stromal Tumors. Diagnostics (Basel) 2021; 11:diagnostics11020194. [PMID: 33525726 PMCID: PMC7912114 DOI: 10.3390/diagnostics11020194] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/21/2021] [Accepted: 01/23/2021] [Indexed: 12/14/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The majority are sporadic, solitary tumors that harbor mutually exclusive KIT or PDGFRA gain-of-function mutations. The type of mutation in addition to risk stratification corresponds to the biological behavior of GIST and response to treatment. Up to 85% of pediatric GISTs and 10–15% of adult GISTs are devoid of these (KIT/PDGFRA) mutations and are referred to as wild-type GISTs (wt-GIST). It has been shown that these wt-GISTs are a heterogeneous tumor group with regard to their clinical behavior and molecular profile. Recent advances in molecular pathology helped to further sub-classify the so-called “wt-GISTs”. Based on their significant clinical and molecular heterogeneity, wt-GISTs are divided into a syndromic and a non-syndromic (sporadic) subgroup. Recently, the use of succinate dehydrogenase B (SDHB) by immunohistochemistry has been used to stratify GIST into an SDHB-retained and an SDHB-deficient group. In this review, we focus on GIST sub-classification based on clinicopathologic, and molecular findings and discuss the known and yet emerging prognostic and predictive genetic alterations. We also give insights into the limitations of targeted therapy and highlight the mechanisms of secondary resistance.
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