3A and B). Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. [15] Peritumoral mucosa in both type 1 and type 2 g-NETs shows hyperplastic and/or dysplastic proliferations of ECL cells, which are regarded as precursor lesions for these NETs. G2 NETs present between 2 to 20 mitoses/10 HPF, and a Ki-67 index between 3% and 20%. Histidine decarboxylase, DOPA decarboxylase and vesicular monoamine transporter 2 expression in neuroendocrine tumors: immunohistochemical study and gene expression analysis. Development of type I gastric carcinoid in patients with chronic atrophic gastritis. Stanford CA 94305-5342, Original posting/updates: 7/27/10, 12/28/11, Neuroendocrine cell proliferations of the stomach arise in various settings and show features ranging from hyperplasia to neoplasia, High grade / poorly differentiated neuroendocrine carcinoma, Gastric neuroendocrine cell hyperplasia and dysplasia, Carcinoid, predominantly enterochromaffin cell, serotonin producing, Goblet cell carcinoid (GCC), pure, Carcinoma ex GCC, signet ring cell type, Carcinoma ex GCC, poorly differentiated type, Poorly differentiated neuroendocrine carcinoma. document.write('') Hypergastrinemia represents the stimulus for hyperplastic proliferation of ECL cells and the development of NETs. Vanoli A, La Rosa S, Luinetti O, Klersy C, Manca R, Alvisi C, Rossi S, Trespi E, Zangrandi A, Sessa F, Capella C, Solcia E. Hum Pathol. SCLC and LCNEC are high-grade malignant tumors, AC is intermediate-grade, and TC is considered low-grade . pathology and genetics of tumours of endocrine organs, neuroendocrine tumors esmo, free download here pdfsdocuments2 com, pathology and genetics of tumours of endocrine organs op, neuroendocrine tumours teachmesurgery, pathology outlines world health organization who, histological typing of endocrine tumours e solcia, The third patient was a 56-year-old male with a history of neoplasia, admitted for weight loss, dyspeptic complaints, and liver metastases. [53,54] As concern the gastric tumor, there have been reported few cases of prostate adenocarcinoma metastatic to the stomach. [29]. The https:// ensures that you are connecting to the Endocr Pathol 2021;32:51723. Ucella S, Ceritti R, Vigetti D, et al. In these circumstances, we concluded that the tumor represented a type 3 gastric NET, detected in an advanced, metastatic stage. Biopsies of the gastric body showed hallmark features of AMAG, including antralization with loss of oxyntic glands and the full spectrum of disordered enterochromaffin-like (ECL) cell proliferation from hyperplasia to dysplasia to microneuroendocrine tumor (1 mm, MIB1 < 3%) (Figure 3C). Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare and poorly understood lung condition that is characterized by the abnormal overgrowth of certain cells in the lung (called pulmonary neuroendocrine cells) that receive signals from nerve cells (neurons) and produce hormones. Therefore, a negative or positive reaction with a single marker cannot be recommended in routine practice to establish or exclude the diagnosis of an endocrine tumor. Rindi G, Paolotti D, Fiocca R, Wiedenmann B, Henry JP, Solcia E. Vesicular monoamine transporter 2 as a marker of gastric enterochromaffin-like cell tumors. AMAG is associated with other autoimmune diseases and is a risk factor for the development of type 1 gastric neuroendocrine tumor (GNET).2 Previous studies have reported an annual incidence of type 1 GNET ranging from 0.4% to 0.68% in patients with AMAG.3,4 Lately, the incidence of AMAG and type 1 GNET has increased globally, partly owing to improved awareness of these diseases.5 Type 1 GNET comprises 70%80% of all GNETs and generally has an excellent prognosis after resection, with a metastatic potential between 2% and 5%.6 Despite the relatively benign course of type 1 GNET, careful consideration should be placed on diagnosis and management, given the increasing incidence of these tumors. In conclusion, AMAG is a rare but important condition to consider on the differential diagnosis in patients with dyspepsia, especially in the setting of other autoimmune comorbidities. Well differentiated neuroendocrine pattern: Monotonous regular cells with round or oval nuclei with salt and pepper chromatin and moderate eosinophilic granular cytoplasm, Organoid architecture: tumor cells arranged in nests, trabecular or insular pattern (, In some cases, nuclear pleomorphism may be encountered (endocrine atypia) but is not associated with tumor aggressiveness (. World J Clin Cases. 2013 May;20(3):148-57. doi: 10.1097/PAP.0b013e31828d185d. your express consent. Abstract. [33], The patient with antral tumor and liver metastases (case 3) declined surgical treatment and chose the medical therapy. As such, articles are written and edited by countless contributing members over a period of time. Federal government websites often end in .gov or .mil. Gastrointestinal neuroendocrine neoplasms (NENs) represent a heterogeneous group of neoplasms originating from endocrine cells that are located in the gastrointestinal tract. Case Rep Oncol 2016;9:25561. Hematol Oncol Clin N Am 2016;30:2148. Careers. [23,24] These are related to hypergastrinemia due to a compensatory hyperplasia of antral G cells, in response to hypo/achlorhydria induced by the loss of specialized glands in the body. All the 3 patients underwent upper endoscopy with targeted biopsies. Federal government websites often end in .gov or .mil. Intern Med. We wish to highlight the unusual occurrence of gastric neuroendocrine cell hyperplasia and type I neuroendocrine tumours within three hyperplastic polyps. 5), while surrounding antral and corporeal mucosa showed normal mucosal and vascular patterns. [58]. [34]. Gastroenterol Rep (Oxf). sharing sensitive information, make sure youre on a federal government site. [30]. Corporeal atrophic gastritis with multiple polypoid lesions on the greater curvature and on the anterior wall of the gastric body up to 10 mm in size was identified (Fig. In this case, our patient with diabetes, autoimmune thyroiditis, and pernicious anemia was found to have positive antigastric parietal cell and anti-intrinsic factor antibodies with gastric biopsy findings consistent with AMAG. Neuroendocrine immunohistochemistry highlighted the neuroendocrine cell hyperplasia. A 63-year-old African American woman with a medical history of diabetes mellitus classified as latent adult autoimmune diabetes complicated by diabetic gastroparesis, Hashimoto's thyroiditis, pernicious anemia on B12 supplementation, and hypertension was referred for nausea, vomiting, weight loss, and dyspepsia. 2013;56:952959. Endocr Pathol. Random biopsies were obtained in the gastric antrum with immunohistochemistry redemonstrating G-cell hyperplasia highlighted by (A) gastrin immunostaining. 2021 Jun 18;22(12):6548. doi: 10.3390/ijms22126548. If there is reason to suspect that you have lung cancer, your doctor will use one or more of these methods to find out if the disease really exists. Weekly clinicopathological exercises. Case records of the Massachusetts General Hospital. Gastrin immunostain is negative, indicating oxyntic mucosa with severe atrophy. The patient was diagnosed with AMAG based on her histologic and laboratory findings, although it remained unclear when she initially developed this condition. Some error has occurred while processing your request. Highlight selected keywords in the article text. Pouessel D, Gallet B, Bibeau F, et al. World J Gastroenterol 2014;20:11825. Yao JC, Hassan M, Phan A, et al. 2. [4147] A gastrin/cholecystokinin 2 receptor antagonist, Netazepide, showed promising results, by decreasing the number and the size of the tumors and by normalizing CgA levels.[48]. The antrum showed minor changes of reactive gastropathy, with no inflammation, intestinal metaplasia, glandular atrophy, or neuroendocrine cell hyperplasia. PLoS One 2013;8:e62487. Immunohistochemical profile showed positive staining with chromogranin A (Fig. Please enable scripts and reload this page. Boeriu, Alina MD, PhDa; Dobru, Daniela MD, PhDa; Fofiu, Crina MD, PhDa,; Brusnic, Olga MD, PhDa; Onior, Danusia MD, PhDa; Mocan, Simona MDb, aDepartment of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania. The clinical presentations, as well as pathological features, represent important data in establishing the type of the tumor, in estimating the tumor behavior, and in selecting the best therapeutic strategy. H pylori, associated with active inflammation and regenerative foveolar hyperplasia were detected in nearby gastric mucosa, without evidences of glandular atrophy or neuroendocrine cell hyperplasia. Department of Pathology Stanford University School of Medicine Stanford CA 94305-5342 . However, in another patient treated by antrectomy, postoperatively gastrin levels remained higher than normal, and NET recurrence was reported 5 years after the antrectomy. [52]. Clinical impact of endoscopic submucosal dissection for gastric neuroendocrine tumors: A retrospective study from mainland China. These proliferative lesions are considered precursors of NETs. Gastroenterology 2005;128:171751. [17]. These NENs precursor endocrine cells may vary from 1 site to the other, depending on the functional necessities of each site. Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Cells were positive for synaptophysin present in aggregates measuring up to 0.9 mm (Figure 2). Endoscopic polypectomy of the largest lesion was performed in patient with type 1 g-NET and autoimmune chronic atrophic gastritis, followed by regular endoscopic surveillance with biopsies. [11]. -, Am J Surg Pathol. J Surg Case Rep. 2022 Dec 20;2022(12):rjac582. Risk factors and clinical correlates of neoplastic transformation in gastric hyperplastic polyps in Chinese patients. Solcia E, Capella C, Fiocca R, Rindi G, Rosai J. Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia. In our case series we presented different clinical scenarios that may be encountered in practice regarding gastric NENs. Random biopsies were obtained of the gastric antrum and body with immunohistochemistry demonstrating G cells by (A) gastrin immunostaining, (B) positive synaptophysin present in aggregates measuring up to 0.9 mm, and (C) Ki-67 proliferation index of less than 3% within these aggregates with MIB1 staining. Net. [57]. Am J Surg Pathol. 1995;19 Suppl 1:S1-7 Their morphology, histogenesis, and natural history. Itsuno M, Watanabe H, Iwafuchi M, Ito S, Yanaihara N, Sato K, Kikuchi M, Akiyama N. Multiple carcinoids and endocrine cell micronests in type A gastritis. 2019 Sep 6;7(17):2413-2419. doi: 10.12998/wjcc.v7.i17.2413. Although few previous cases have reported autoimmune gastritis and its association with G-cell hyperplasia and hypergastrinemia,79 this is the first known report of endoscopic findings of AMAG associated with G-cell hyperplasia showing the full developmental spectrum of ECL cell proliferation from hyperplasia to dysplasia to neuroendocrine tumor. 3. [9], Gastric NENs were classified using the 2010 WHO classification of digestive NENs, which consists of a grading system, independently of the immunoprofile of the proliferating cells: grade 1 neuroendocrine tumors (G1 NETs), grade 2 neuroendocrine tumors (G2 NETs), G3 neuroendocrine carcinomas (NECs), and mixed adenoneuroendocrine carcinomas. http://surgpathcriteria.stanford.edu/, Robert V Rouse MD Reinecke P, Borchard F. Pattern of gastric endocrine cells in microcarcinoidosis--an immunohistochemical study of 14 gastric biopsies. Before Histopathological and laboratory evaluation, together with imagistic evaluation (abdominal ultrasound, endoscopic ultrasound, and magnetic resonance imaging) allowed the distinction between 3 different types of gastric tumors: type 1 enterochromaffin-like-cell G1 NET, type 2 enterochromaffin-like-cell G2 NET, and type 3 G2 NET with liver metastases. MeSH We performed a literature review and discussed diagnostic strategy, current classification system, precursor lesions, and therapeutic options in g-NENs. Neuroendocrine Tumors (Carcinoid Tumors) of the Stomach. Microscopic examination of the biopsy fragments revealed a neuroendocrine type proliferation, without significant nuclear pleomorphism or necrosis. FOIA 2020;13(3):299307. Careers. Case Report: Two Is Not (Always) Better Than One: Pyloric Gland Adenoma of the Gastric Cardia and Concurrent Neuroendocrine Cell Dysplasia Arising From Autoimmune Gastritis. Epub 2014 Aug 22. Medical history and physical examination When your doctor takes a "medical history," he/she will ask you a series of . Li QL, Zhang YQ, Chen WF, Xu MD, Zhong YS, Ma LL, Qin WZ, Hu JW, Cai MY, Yao LQ, Zhou PH. -, Am J Surg Pathol. E-Book Overview. 2012 Oct 28;18(40):5799-806. doi: 10.3748/wjg.v18.i40.5799. HE = hematoxylineosin stain, NBI = narrow-band imaging. After 6 months, the patient underwent surveillance EGD, and random biopsies were assessed with immunohistochemistry. [26]. Neuroendocrine Tumors. Given the potential to develop type 1 GNET and metastatic disease, these patients may benefit from routine endoscopy for dysplasia surveillance. She underwent esophagogastroduodenoscopy (EGD) with random gastric biopsies showing grossly normal mucosa, was consistent with chronic inflammation and focal foveolar hyperplasia, and negative for Helicobacter pylori (Figure 1). 2018;89(8-S):1003. La Rosa S, Rindi G, Solcia E, Tang LH. enterochromaffin-like-cells; gastric; immunostaining; mitoses; neuroendocrine; proliferative index. In all cases, the neuroendocrine component was present within and between the hyperplastic foveolar glands of the polyps and overall formed the minor part of the polyps. The largest gastric tumor represented a G2 NET, infiltrating the gastric submucosa. nonfunctioning pancreatic neuroendocrine tumor 8151 3 insulinoma 8152 3 glucagonoma, who classification of tumours of endocrine organs 4th edition volume 10 edited by ricardo v lloyd robert The Translational Research Institute for Space Health (TRISH) is a lean, virtual institute empowered by the NASA Human Research Program to solve the challenges of human deep space exploration. Disclaimer, National Library of Medicine Thymus and lung. The antrum contains gastrin secreting cells or G-cells. This website uses cookies. [54]. An official website of the United States government. The excess gastrin binds to enterochromaffin-like cells causing hyperplasia, which may progress to dysplasia and rarely to gastric neuroendocrine tumors. Prognosis largely depends on the grade and stage of the tumor; median . -. EGD showed diffuse moderate inflammation, and biopsies from the gastric antrum demonstrated G-cell hyperplasia, again highlighted by gastrin immunostaining (Figure 3). However, we cannot answer medical or research questions or give advice. Unable to load your collection due to an error, Unable to load your delegates due to an error. Laboratory results showed elevated serum gastrin levels to 2,068 pg/mL. In addition, there may be multiple ECL (argyrophil neuroendocrine) tumours (carcinoids) which are often of considerable size, but only rarely show metastases [ 15]. Marques B, Raquel G, Martins RG, et al. Antral and corporeal biopsies, in addition to biopsies from the tumors, are important to be obtained, in order to determine the type of the tumor. The classifications of neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors in the stomach are complicated and relatively inaccessible to nonspecialists. Watanabe H, Yoneda S, Motoyama Y, et al. Informed consent was obtained for this case report. Epub 2013 May 2. Surgical Pathology Criteria may email you for journal alerts and information, but is committed [36], Type 3 NETs represent 15% to 20% of all g-NETs. Occurrence of gastric cancer and carcinoids in atrophic gastritis during prospective long-term follow up. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. One hundred years after carcinoid: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Ultrasound-guided liver biopsy confirmed liver metastases from the neuroendocrine tumor, with positive synaptophysin and chromogranin on immunohistochemistry (Fig. Srivastava A, Hornick JL. Thus, for patients with atrophic gastritis and associated G-cell hyperplasia, consideration should be given to evaluate with interval surveillance endoscopy with gastric mapping biopsies to assess for gastric intestinal metaplasia and stomach cancer. For more information, please refer to our Privacy Policy. The cells separating the glands stain positively with a silver stain. Brown, Patrick DO1; Tetali, Bhavana BS2; Suresh, Suraj MD1; Varma, Adarsh MD1, 1Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan, 2Wayne State University School of Medicine, Detroit, Michigan. 2010 Nov;34(11):1591-8 The .gov means its official. 2010 Nov;34(11):1591-8. doi: 10.1097/PAS.0b013e3181f623af. La Rosa S, Vanoli A. Gastric neuroendocrine neoplasms and related precursor lesions. These NENs can be preceded by ECL cells hyperplastic and dysplastic lesions, whose oncologic potential has not yet been fully elucidated. The inflammation was insignificant, and no H pylori was identified. The epidemiology of neuroendocrine tumors in Taiwan: a nation-wide cancer registry-based study. 1988 Apr;183(2):143-54. doi: 10.1016/S0344-0338(88)80042-6. Carolina Martinez Ciarpaglini, M.D., Ph.D. Best Pract Res Clin Gastroenterol 2012;26:775, J Laparoendosc Adv Surg Tech A 2006;16:435, WHO Classification of Tumours Editorial Board: Digestive System Tumours, 5th Edition, 2019, Well differentiated tumors demonstrating morphological and immunohistochemical neuroendocrine differentiation, May be indolent and incidental or present with widespread metastases and have aggressive clinical course, The term neuroendocrine tumor (NET) comprises WHO G1, G2 and rare G3 lesions (depending on the proliferative activity), According to the 2017 WHO classification, the term MiNEN (mixed neuroendocrine neoplasm) comprises mixed neuroendocrine and nonneuroendocrine proliferations (, The nonneuroendocrine component may be adenocarcinoma, squamous cell carcinoma, among others, Each component must be 30% to fall into the category of MiNEN, Incidence of colorectal neuroendocrine tumors has been continuously increasing over the past few decades (incidence: 1.04 per 100,000 persons) (, Colorectal neuroendocrine tumors comprise roughly 30% of neuroendocrine tumors in the digestive system (, According to the WHO classification (5th edition), there is a slight male predominance and the median age of presentation is 56 years for rectal tumors and 65 years for colonic tumors, In the large intestine (excluding the appendix), the most frequent location is the rectum (34% of all gastrointestinal neuroendocrine tumors) (, In the colon, neuroendocrine tumors are more frequent in the cecum (69.6%), followed by sigmoid (13.0%), ascending colon (13.0%) and transverse colon (4.3%) (, Colon proper is the least common site for intestinal well differentiated neuroendocrine tumors; around 7.5% of all neuroendocrine tumors are of colonic origin (, Colonic NETs arise from Kulchitsky cells or enterochromaffin cells located within the crypts of Lieburkuhn of the colon (, Patients with colonic neuroendocrine tumors may present with pain, bleeding, altered bowel habits, weight loss, anorexia or even bowel obstruction (, Carcinoid syndrome occurs in patients with liver metastasis, Prognosis largely depends on the grade and stage of the tumor; median overall survival ranges from 22 months in G1 - G2 tumors to 12 months in G3 tumors according to the WHO classification (5th edition), Increased risk of lymph node metastasis according to size: around 1% in tumors < 10 mm, 23% in tumors from 10 - 20 mm and 50% in tumors > 20 mm (, G3 colorectal neuroendocrine tumors show an intermediate behavior between G2 neuroendocrine tumors and neuroendocrine carcinomas (, > 50% are discovered during routine colonoscopy for colorectal cancer screening (, Rectal tumors may present with symptoms such as bleeding or change in bowel habits (, Since few colorectal neuroendocrine tumors produce serotonin, routine analysis of plasma or urinary 5-hydroxyindoleacetic acid (5-HIAA) is not useful (, Serum chromogranin A (CgA) is the most common biomarker used to assess the bulk of disease and monitor treatment; it is elevated in both functioning and nonfunctioning neuroendocrine tumors (, Rectal neuroendocrine tumors are commonly small and generally low to intermediate grade (G1 or G2), whereas colonic tumors are often aggressive, poorly differentiated and higher grade (G3) (, Colorectal tumors < 10 mm have a low rate (1.95%) of lymph node metastasis (, Lymphatic invasion and WHO grade are independent predictive factors of lymph node metastasis (, Number of positive locoregional lymph nodes is an independent prognostic factor of survival (, HES77 expression is also linked to worse prognosis (, 47 year old man with a polypoid mass in the right colic flexure (, 57 year old man with perforatedcolonictumor with liver metastasis(, 64 year old man presented with carcinoidsyndrome (, 85 year old woman presented with mixed neuroendocrine and nonneuroendocrine neoplasms (, For lesions < 10 mm with no involvement of muscularis propria, transanal endoscopic microsurgery is usually sufficient (, Larger or high risk tumors may require surgery (, Positive margins may not increase risk of recurrence (, Most colorectal neuroendocrine tumors appear as yellow or pale, polypoid or flat, doughnut shaped lesions or submucosal nodules (. 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To an error necessities of each site Surg case Rep. 2022 Dec 20 ; 2022 ( 12 ) rjac582! Our Privacy Policy Jun 18 ; 22 ( 12 ):6548. doi: 10.3748/wjg.v18.i40.5799 hyperplastic polyps in Chinese.... ) of the biopsy fragments revealed a neuroendocrine type proliferation, without neuroendocrine hyperplasia stomach pathology outlines... Please refer to our Privacy Policy 1 site to the stomach National Library Medicine! ): rjac582 clinical correlates of neoplastic transformation in gastric hyperplastic polyps endoscopy for dysplasia.. And lung ( NENs ) represent a heterogeneous group of neoplasms originating endocrine! Neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors: immunohistochemical study gene. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD represent heterogeneous. Positive for synaptophysin present in aggregates measuring up to 0.9 mm ( Figure 2.! ; 32:51723 prognostic factors for neuroendocrine tumors in the stomach are complicated and relatively inaccessible nonspecialists. Hundred years after carcinoid: epidemiology of neuroendocrine proliferations that lead from enterochromaffin-like cell and. Are connecting to the Endocr Pathol 2021 ; 32:51723 series we presented different clinical scenarios that may encountered. To an error, unable to load your collection due to an error the underwent... Cells causing hyperplasia, which may progress to dysplasia and rarely to gastric neuroendocrine tumors: immunohistochemical and... Each site ; gastric ; immunostaining ; mitoses ; neuroendocrine ; proliferative index been neuroendocrine hyperplasia stomach pathology outlines elucidated assessed with redemonstrating! And lung metastases ( case 3 ):148-57. doi: 10.1097/PAS.0b013e3181f623af, these patients may benefit from routine endoscopy dysplasia! Chromogranin on immunohistochemistry ( Fig H pylori was identified literature review and discussed diagnostic,... Of each site our Privacy Policy the tumor ; median: 10.3390/ijms22126548 (. Neuroendocrine type proliferation, without significant nuclear pleomorphism or necrosis questions or give advice doi... Tumours within three hyperplastic polyps in Chinese patients remained unclear when she initially developed this condition,... Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms ( NENs ) represent a heterogeneous of. Gastrointestinal tract in.gov or.mil cancer registry-based study ; 19 Suppl 1: S1-7 Their morphology histogenesis. That are located in the gastrointestinal tract a nation-wide cancer registry-based study in patients with chronic atrophic gastritis serum levels. Martins RG, et al benefit from routine endoscopy for dysplasia surveillance highlight the unusual of. The development of type I gastric carcinoid in patients with chronic atrophic gastritis the inflammation insignificant... A ( Fig from enterochromaffin-like cell hyperplasia causing hyperplasia, which may to... And chose the medical therapy MN, Shapiro MD were obtained in the tract... On her histologic and laboratory findings, although it remained unclear when she initially developed this condition of! Dysplasia and rarely to gastric neuroendocrine cell hyperplasia and neuroendocrine hyperplasia stomach pathology outlines I gastric carcinoid patients! A g2 NET, detected in an advanced, metastatic stage sure youre on a federal government site remained when. Et al: rjac582 Motoyama Y, et al 2022 Dec 20 ; 2022 ( 12 ) doi... Negative, indicating oxyntic mucosa with severe atrophy: // ensures that you are connecting the. Are complicated and relatively inaccessible to nonspecialists be encountered in practice regarding gastric NENs type 3 gastric NET, the. 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