tufting enteropathy pathology outlines

Congenital Tufting Enteropathy is a rare congenital enteropathy presenting with early-onset severe and intractable diarrhea that leads to irreversible intestinal failure. CTE: congenital tufting enteropathy; PN: parenteral nutrition; ITx: intestinal transplantation. In addition, almost no inflammatory cell infiltration was found in the lamina propria, while in some cases reported elsewhere, the numbers of inflammatory cells could increase in the lamina propria, suggesting that the increase in inflammatory cells is not a criterion for CTE exclusion [34]. General. History. CTE patients could also show extraintestinal symptoms, which are defined as a syndromic form of CTE (SCTE) [17]. One study showed that EpCAM plays a critical role in forming functional tight junctions in the intestinal epithelium by recruiting claudin protein [40]. Only four of the mutations were reported in two or more patients: c.488A>G (24 patients), c.2T>C (2 patients), c.442C>T (2 patients), and c.502G>A (2 patients). Compiled by the Intestinal Care and Rehabilitation team within the Gastroenterology Department in collaboration with the Child and Family Information Group Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London WC1N 3JH www.gosh.nhs.uk. Jump to navigation Jump to search. H&E stain. Histological examination of the small bowel shows varying degrees of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria. Accordingly, the protein could not be detected by immunohistochemistry in intestinal biopsies [16, 19, 45]. Features: Villous atrophy; Mononuclear cell infiltration of the lamina propria; Abnormal surface enterocytes: Focal crowding -- resembling tufts. 1 Departments of *Pathology †Pediatrics, Division of Gastroenterology, ... congenital tufting enteropathy (intestinal epithelial dysplasia), and enteroendocrine cell dysgenesis, a series of duodenal biopsies from 26 pediatric patients with chronic/intractable diarrhea was retrospectively reviewed. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000–100,000 live births in Western Europe. Am J Surg Pathol. A. Kerner, F. K. Hazard, and T. A. Longacre, “Evaluation of intestinal biopsies for pediatric enteropathy: a proposed immunohistochemical panel approach,”. The low incidence of CTE and the paucity of related studies have caused the disease to remain elusive, and CTE patients still suffer from poor prognosis and low quality of life. 59 year old Caucasian man admitted to the hospital with complaints of intractable diarrhea, vomiting and considerable weight loss (Am J Case Rep 2019;20:111) 68 year old Caucasian woman with a history of hypertension with recurrent episodes of acute intermittent diarrhea, nausea, vomiting, renal failure and 15 lbs … Congenital Tufting Enteropathy (CTE) [Online Mendelian Inheritance in Man (OMIM): 613217], is a rare intractable diarrheal disease of infancy characterized by profuse watery diarrhea, electrolyte imbalances, and impaired growth [1, 2]. Changes in the formula of full-calorie enteral nutrition, such as carbohydrate-free formula or amino acid-based formula, usually fail to reverse the weight loss caused by diarrhea [23]. Pathology. The most important feature involves the epithelium where the surface enterocytes are disorganized with … .style1 { Life-threatening diseases that require indefinite parenteral nutrition, such as CTE, suggest timely ITx for patients with the following situation: 2 admissions to an intensive care unit (after initial recovery from the event inducing IF) because of cardiorespiratory failure (mechanical ventilation or inotrope infusion) due to sepsis or other complications of IF [64]. This mutation resulted in reduced inhibitor activity of SPINT2 on the prototype serine protease trypsin. 2008 Aug;135(2):429-37. Intractable diarrhea is present in the first few weeks or months after birth, independent of breast or formula feeding. In most patients, typical abnormalities are localized mainly in the surface epithelium, forming focal epithelial “tufts” [13, 18]. http://surgpathcriteria.stanford.edu/, , Robert V Rouse MD However, in some CTE patients exhibiting isolated diarrhea, neither EpCAM nor SPINT2 mutations were detected. In general, infants suspected to have CTE undergo esophagogastroduodenoscopy and colonoscopy examination, during which mucosal biopsies are performed at multiple sites. Characteristically, these patients could show unilateral or bilateral choanal atresia at birth [2], accompanied by ophthalmologic diseases throughout life [6]. Existing studies have confirmed that mutations in EpCAM and SPINT2 are the two leading causes of CTE, while a small number of CTE patients did not harbor either EpCAM or SPINT2 mutations, suggesting that other genes might be responsible for these CTE patients, which requires further research. Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. Matriptase, prostasin, SPINT1, and SPINT2 are coexpressed in most developing and adult mammalian epithelia. In addition, mutations in SPINT2 have been indicated to indirectly induce the loss of EpCAM protein due to proteolysis by activating matriptase [50]. Since then, changes have been made in the management of IF, bringing about advances in transplantation and improvement in patient survival. 2007 Oct;16(4):211-21; Al-Mayouf SM, Alswaied N, Alkuraya FS, Almehaidib A, Faqih M. Tufting enteropathy and chronic arthritis: a newly recognized association with a novel EpCAM gene … PubMed PMID: 25188866. A study on how different mutation types affect prognosis suggested that the frameshift mutation group (particularly c.498insC), the only group with a significant difference, was more likely to require full TPN and was associated with more severe clinical outcomes. In 2008, genetic studies on 11 CTE patients identified disease-related mutations in the gene encoding human epithelial cell adhesion molecule (EpCAM), which is located on chromosome 2p21 (47,369,147 to 47,387,027) [7]. EpCAM has long been described as a molecule involved in the interactions between cells, similar to most other cell adhesion molecules. This cellular assay assessed the proteolytic activity of matriptase and prostasin using the epithelial sodium channel ENaC as a reporter gene. Typically, patients develop watery diarrhea within the first days after birth and have the characteristic appearance of subtotal villous atrophy with crypt hyperplasia and tufting of the epithelial surface (7) . Less frequently, superficial punctuated keratitis, anal atresia, cleft lip and palate, dermatological anomalies, and bone malformations could be observed. julie.lemale@trs.aphp.fr Comment in J Pediatr … The infiltrate shows a varying cytologic composition with an admixture of small, medium, and larger atypical lymphoid cells. Clinically, patients with EpCAM mutations mainly present isolated congenital diarrhea without parenteral symptoms [16]. These include microvillus inclusion disease, tufting enteropathy, autoimmune enteropathy and IPEX syndrome - and it is these conditions that are the subject of the current review. 2011 Sep;53(3):355. doi: 10.1097/MPG.0b013e318228841a. In contrast, mutations of splice sites, particularly c.556-14A>G, were more frequently observed in patients requiring partial TPN, suggesting better clinical outcomes [60]. No epidemiological data is available, however, the prevalence can be estimated at around 1/200,000 births in Europe. The MIF method includes an antigen-retrieval step followed by multilabel immunostaining and examination by confocal microscopy. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Congenital tufting enteropathy (CTE), also named intestinal epithelial dysplasia, is a rare, autosomal recessive enteropathy belonging to secretory CDD . Initially, the oocyte system was used to assess the activity of the intestinal serine proteases matriptase and prostasin and their inhibition induced by SPINT2 and its missense mutant (c.488A>G, p.Tyr163Cys) associated with SCSD. Enteropathy-associated T-cell lymphoma (EATL) is highly associated with celiac diseaes, and shows a similar epidemiology on a world-wide basis. The epithelial cell adhesion molecule … It presents clinical and histological heterogeneity and may be associated with … Tufting enteropathy (TE), also known as intestinal epithelial dysplasia, is 1 of the causes of intractable diarrhea in neonates .First described in 1994 by Reifen et al , TE is a congenital abnormality of intestinal mucosa development characterized by a specific histological pattern of persistent villous atrophy and epithelial dysplasia.It is probably inherited on an autosomal … This report describes a case of refractory enteropathy with circulating intestinal goblet cell autoantibodies (IGA). All authors read and approved the final manuscript. Tufting Enteropathy: Microvillus Inclusion Disease: Surface epithelial tufts: Apical cytoplasmic inclusions: Both may have scant inflammation with villous atrophy Enteroendocrine Cell Dysgenesis: Microvillus Inclusion Disease: Normal villi: Severe villus atrophy: Intestinal endocrine cells markedly decreased or absent: Normal intestinal endocrine cells: Normal enterocyte … Tufting enteropathy (TE), previously known as intestinal epithelial dysplasia, is a rare congenital enteropathy characterized by refractory diarrhea in the neonatal period. Newborn screening; blood tests for liver, kidney, and pancreas function; imaging methods; and immunologic, allergic, and extensive laboratory work up could not identify the etiology for CTE patients [25]. Tufting enteropathy (TE), also known as intestinal epithelial dysplasia (IED), is a congenital enteropathy presenting with early-onset severe intractable diarrhea and persistent villous atrophy with low or no mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium. Congenital tufting enteropathy. … The diarrhoea did not improve despite fasting under total parenteral nutrition. Abstract: Tufting enteropathy (TE) is an uncommon disease causing intractable diarrheas starting in early childhood and resulting in failure to thrive, dependence on total parenteral nutrition, and eventually requiring transplantation for treatment. font-family: Arial, Helvetica, sans-serif; Most patients with CTE rely on total parenteral nutrition (TPN) for energy support, while in severe cases, small bowel transplantation is required [7, 8]. The first criteria for ITx was published in the American Society of Transplantation [63]. Tufting enteropathy is a rare autosomal recessive disorder presenting with early-onset severe intractable diarrhea. As examples, w … Stanford CA 94305-5342, Original posting / last update: 11/11/09, 1/17/15, Neonatal enteropathy with characteristic surface epithelial tufted appearance, Severe intractable diarrhea presents in first days of life, Surface epithelial disorganization with focal crowding and extrusion of cells and apical cytoplasm or “tufting”, Surface epithelial crowding and tufting at villus tips, Markedly decreased or absent endocrine cells. Focal epithelial tufts are typically found in the small intestine and occasionally in the colonic mucosa [10]. Congenital tufting enteropathy (CTE), also known as epithelial dysplasia , is an autosomal recessive disorder causing severe diarrhoea in the first week of life together with various dysmorphic features including choanal atresia, oesophageal/rectal atresia in some of the affected infants [6, 7, 17]. Previous studies of CTE in mice expressing mutant EpCAM show neonatal lethality. A new syndrome of tufting enteropathy and choanal atresia, with ophthalmologic, hematologic and hair abnormalities. Tufting Enteropathy: A Review of Clinical and Histological Presentation, Etiology, Management, and Outcome, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China, Choanal atresia; ophthalmologic, hematologic, and hair abnormalities, Corneal erosions, hypertelorism, choanal atresia, imperforate anus, rectovaginal fistula, short and brittle hair, and mild psychomotor delay, Oligoarticular juvenile rheumatoid arthritis, Ophthalmic functional disorders, asymptomatic conjunctival hyperemia, Choanal atresia, hyponatremia, and superficial punctate keratitis, Superficial punctuated keratitis, choanal atresia, other atresia, dermatological anomalies, and bone malformations, Cleft lip and palate, corneal erosions, optic nerve coloboma, and intermittent exotropia, Choanal atresia, enterocutaneous fistula, atrial septal defect, cleft lip and palate, and toe abnormalities, Hepatocyte growth factor activator inhibitor type 2, G. Terrin, R. Tomaiuolo, A. Passariello et al., “Congenital diarrheal disorders: an updated diagnostic approach,”, P. Heinz-Erian, T. Müller, B. Krabichler et al., “Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea,”, R. Berni Canani, G. Terrin, G. Cardillo, R. Tomaiuolo, and G. Castaldo, “Congenital diarrheal disorders: improved understanding of gene defects is leading to advances in intestinal physiology and clinical management,”, M. Field, “Intestinal ion transport and the pathophysiology of diarrhea,”, P. M. Sherman, D. J. Mitchell, and E. Cutz, “Neonatal enteropathies: defining the causes of protracted diarrhea of infancy,”, O. Roche, M. Putterman, J. Salomon et al., “Superficial punctate keratitis and conjunctival erosions associated with congenital tufting enteropathy,”, M. Sivagnanam, J. L. Mueller, H. Lee et al., “Identification of EpCAM as the gene for congenital tufting enteropathy,”, A. S. Paramesh, T. Fishbein, A. Tschernia et al., “Isolated small bowel transplantation for tufting enteropathy,”, W. Tang, T. Huang, Z. Xu, and Y. Huang, “Novel mutations in EPCAM cause congenital tufting enteropathy,”, O. Goulet, M. Kedinger, N. Brousse et al., “Intractable diarrhea of infancy with epithelial and basement membrane abnormalities,”, O. Goulet, J. Salomon, F. Ruemmele, N. P. M. de Serres, and N. Brousse, “Intestinal epithelial dysplasia (tufting enteropathy),”, S. M. Al-Mayouf, N. Alswaied, F. S. Alkuraya, A. AlMehaidib, and M. Faqih, “Tufting enteropathy and chronic arthritis: a newly recognized association with a novel EpCAM gene mutation,”, R. M. Reifen, E. Cutz, A. M. Griffiths, B. Y. Ngan, and P. M. Sherman, “Tufting enteropathy: a newly recognized clinicopathological entity associated with refractory diarrhea in infants,”, M. Sivagnanam, T. Schaible, R. Szigeti et al., “Further evidence for EpCAM as the gene for congenital tufting enteropathy,”, J. S. Ko, J. K. Seo, J. O. Shim, S. H. Hwang, H. S. Park†, and G. H. Kang†, “Tufting enteropathy with EpCAM mutations in two siblings,”, J. Salomon, O. Goulet, D. Canioni et al., “Genetic characterization of congenital tufting enteropathy: EpCAM associated phenotype and involvement of SPINT2 in the syndromic form,”, M. Sivagnanam, A. R. Janecke, T. Müller, P. Heinz-Erian, S. Taylor, and L. M. Bird, “Case of syndromic tufting enteropathy harbors SPINT2 mutation seen in congenital sodium diarrhea,”, W. El-Matary, A. M. Dalzell, G. Kokai, and J. E. Davidson, “Tufting enteropathy and skeletal dysplasia: is there a link?”, J. Salomon, Y. Espinosa-Parrilla, O. Goulet et al., “A founder effect at the EPCAM locus in congenital tufting enteropathy in the Arabic Gulf,”, I. W. Booth, G. Stange, H. Murer, T. R. Fenton, and P. J. Milla, “Defective jejunal brush-border Na, O. J. Goulet, N. Brousse, D. Canioni, J. Another EpCAM knockout mouse model constructed by a rigorous gene-trapping approach showed intestinal tufts, villous atrophy, and severe hemorrhagic diarrhea. Tufting Enteropathy: Microvillus Inclusion Disease: Surface epithelial tufts: Apical cytoplasmic inclusions: Both may have scant inflammation with villous atrophy Enteroendocrine Cell Dysgenesis: Microvillus Inclusion Disease: Normal villi: Severe villus atrophy: Intestinal endocrine cells markedly decreased or absent: Normal intestinal endocrine cells: Normal enterocyte … Atresia, such as choanal atresia [2, 16, 28, 29], anal atresia [16, 30], and other atresias [16], is another commonly seen parenteral symptom. Rare inherited disorders such as microvillous inclusion disease and tufting enteropathy cause profound malabsorption. A decreased level of SPINT2 mRNA and its abnormal splicing were observed, which indicated the loss-of-function of SPINT2 caused by mutation. [journals.lww.com] There was no … The EpCAM gene mutations were later confirmed by subsequent studies on CTE patients [14–16]. Autoimmune Enteropathy. However, recent experiments failed to prove the oligomerization of EpCAM protein in vitro [37] and the role of EpCAM in adhesion in carcinoma cells [38]. The study showed decreased expression of both EpCAM and claudin-7 as well as disappearance of their colocalization in EpCAM mutation mice. document.write('' + emailE + '') Moreover, missense mutations were reported to manifest as weak EpCAM immunostaining [16] or the disappearance of EpCAM immunohistochemical signals [9]. We are committed to sharing findings related to COVID-19 as quickly as possible. Other than ophthalmologic signs and atresia, patients with CTE could have cleft lip and palate [2, 31], dermatological anomalies [16], bone malformations [16], optic nerve coloboma [31], cholestatic liver disease [17], chronic arthritis [12, 32], and skeletal dysplasia [18]. 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