Predictive value of epithelial lesion heterogeneity in the etiological diagnosis of chronic inflammatory bowel disease

Predictive value of epithelial lesion heterogeneity in the etiological diagnosis of chronic inflammatory bowel disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive value of epithelial lesion heterogeneity in the etiological diagnosis of chronic inflammatory bowel disease Habsatou ABDOULAYE BIYOU, Meryem Zaryouhi, Imane FADLALLAH, Hind BOURKHIME, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9304837/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Introduction : Chronic inflammatory bowel diseases (IBD) are characterized by chronic, intermittent, and continuous inflammation of a part of the digestive tract, with an increased risk of dysplasia and colorectal cancer (CRC). They typically include Crohn's disease (CD) and ulcerative colitis (UC). The diagnosis of IBD is multidisciplinary. One biopsies are essential for establishing a diagnosis, monitoring treatment, and/or identifying complications. This study evaluates the predictive value of the heterogeneity of epithelial abnormalities in the etiological diagnosis of IBD. Materials and Methods : This is a retrospective study involving 81 cases of IBD diagnosed at the Department of Pathological Anatomy and Cytology of the Hassan II University Hospital in FES from 2021 to 2023. The diagnosis was established after histological examination. The homogeneous or heterogeneous nature of the lesions between differents biopsy sample was categorized into two groups. Correlations were made between the presence of homogeneous or heterogeneous characteristics of the lesions and the various epithelial abnormalities, as well as the clinical diagnosis of CD and UC. The positive and negative predictive values were assessed. Results : Our study included 81 cases of IBD. The average age of the patients was 40 years with a standard deviation of 14. All patients underwent colonic biopsy. These 81 cases were distributed as follows based on the final clinical diagnosis: 19 cases of CD, 59 cases of UC, and 3 cases of IBD on histological examination. When endoscopic and histopathological data were correlated, heterogeneous lesions were found in 44% of patients with CD compared to 16% with homogeneous characteristics. In UC, homogeneous lesions were found in 84% of patients compared to 56% with heterogeneous characteristics (P = 0.009). Conclusion : Our study demonstrated that the homogeneous nature of epithelial abnormalities was more commonly observed in UC than in Crohn's disease. This could serve as a discriminatory histological criterion for better categorizing IBD. Crohn's disease Ulcerative Colitis Predictive Value Heterogeneity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Inflammatory Bowel Diseases (IBD) are characterized by chronic, intermittent, or continuous inflammation of a portion of the digestive tract with an increased risk of dysplasia and colorectal cancer (CRC). They are relatively common, often starting between the ages of 15 and 30, and affecting both men and women equally. The first description of IBD dates back to 1932 when Burrill Bernard Crohn published his article "Regional ileitis: A pathologic and clinical entity [ 1 , 2 ]. Histopathology plays a crucial role in the diagnosis, and histological examination is typically based on biopsy samples, which involve only the mucosa and the superficial part of the submucosa. The radiological signs of Crohn's disease include thickening of the intestinal wall, especially in the terminal ileum, ulcers, fistulas, and the presence of skip lesions (areas of intestinal lesions interspersed with healthy segments) [ 3 ]. Histologically, this disease is characterized by discontinuous lesions, which may appear as affected segments with areas of healthy mucosa in between. Crohn's disease can affect any part of the gastrointestinal tract, from the mouth to the anus, and may also involve areas other than the colon, such as the terminal ileum. Histological features include transmural inflammation, spanning the entire intestinal wall, and the presence of granulomas, often located in the submucosa, making their detection difficult on superficial biopsies [ 1 ]. Ulcerative colitis (UC) is radiologically characterized by thickening of the colon and rectum walls, accompanied by ulcers and superficial wounds [ 3 ]. In UC, inflammation affects the rectocolonic mucosa continuously, without interruptions, and is generally limited to the colon and rectum, although it may start in the rectum and gradually spread to the colon. This condition is characterized by continuous and superficial inflammation of the colonic mucosa, without involvement of all layers of the intestinal wall. Unlike Crohn's disease, granulomas are not observed in UC, which is a significant distinction between the two conditions [ 1 ]. In both subtypes of IBD, the infiltrate is primarily mononuclear, with a predominance of lymphocytes and plasma cells. The presence of neutrophils indicates an active disease [ 1 ]. The continuous development of colonoscopy technology has allowed clinicians to have a better view of the colon, providing pathologists with more material [ 3 ]. The diagnosis of IBD and other inflammatory conditions of the colon cannot be established when only one or a few features are present, given the lack of specific histological signs [ 4 ]. Most abnormal biopsies of the colonic mucosa do not provide a specific etiological diagnosis but rather show a pattern of injury. An essential part of the diagnosis is the distribution pattern of the disease. Ulcerative Colitis (UC) is characterized by continuous, homogeneous lesions without any intervening healthy mucosa. On the other hand, focal lesions are more indicative of Crohn's disease (CD) but can also be observed in ischemic colitis and UC [ 5 ]. However, normal endoscopic results do not necessarily reflect normal histology. The correlation between endoscopy and histology is weak, and up to one-third of patients with CD and ulcerative colitis in endoscopic remission may show signs of persistent histological activity [ 1 , 6 , 7 ]. An accurate assessment of microscopic disease activity using respective scoring indices is, therefore, necessary. The aim of our study is to correlate the final diagnosis based on clinical and endoscopic data with the heterogeneity of epithelial lesions in the etiological diagnosis of IBD. We also aim to evaluate the positive predictive value and negative predictive value of heterogeneity in diagnosing CD and UC. Materials and Methods This is a retrospective study involving 81 cases of IBD diagnosed at the Department of Pathological Anatomy and Cytology of Hassan II University Hospital in FES. The diagnosis was established based on fragments of endoscopic colonic biopsy fixed in 10% formalin, processed using conventional methods, and embedded in paraffin blocks. Sections of these blocks were stained with hematoxylin and eosin saffron (HES) following standard procedures. The inclusion criteria included an ileo-colonic biopsy, availability of endoscopic and clinical data, and the presence of sufficient histological criteria for diagnosis. Exclusion criteria were the unavailability of endoscopic data and insufficient histological criteria to confirm the diagnosis. Biopsies were obtained without orientation. Biopsied segments included the rectum in 23 cases, the ileocecal valve in 4 cases, and in 54 cases, the pathological colon without precise localization. In Crohn's disease, biopsies of the terminal ileum were performed in 4 cases. Slides were annotated by two experienced gastrointestinal pathologists. After an initial histological study, a review of HES slides was conducted by a second experienced gastrointestinal pathologist to thoroughly analyze the various epithelial abnormalities and lesion heterogeneity. The heterogeneity of lesions was categorized into two groups: homogeneous or heterogeneous. A degree of heterogeneity of lesions was observed within a single biopsy, which was classified into two groups: homogeneous and heterogeneous. Definition of terms: In the context of inflammatory bowel diseases (IBD), lesion heterogeneity refers to the diversity of observed tissue alterations, including their location, type, depth, and histological appearance. This variability can have significant implications for the diagnosis, treatment, and prognosis of patients with these inflammatory intestinal conditions. A lesion is considered homogeneous when the entire or the majority of the sample exhibits a uniform appearance upon examination. This means that the entirety or most of the examined area is abnormal. A lesion is termed heterogeneous when an irregular or varied appearance is present upon examination, indicating that a portion of the sample (or fragment) is entirely normal while another part is abnormal. Correlations were made between the presence of homogeneous or heterogeneous characteristics of the lesions and various epithelial abnormalities, as well as the clinical diagnosis of CD and UC. Positive and negative predictive values were also evaluated. Various epithelial abnormalities included architectural anomalies such as loss of crypt parallelism, bifurcation, branching, cystic change, atrophy, dedifferentiated gland appearance, as well as surface villi appearance and dysplastic lesions. The type of inflammatory infiltrate was also examined. Statistical analysis was performed using SPSS software version 26, and a correlation was considered significant if p < 0.05. The tests conducted included Pearson's chi-square test, Fischer's exact test, and the student's t-test (T-test). Descriptive statistics such as mean, standard deviation, and percentages were calculated to characterize the studied sample. A Pearson correlation analysis was used to assess the presence of homogeneous or heterogeneous lesion characteristics with various epithelial anomalies and the clinical diagnosis of CD and UC. Fischer's t-test and the Student's t-test were used to compare epithelial anomalies between CD and UC. Results Our study included 81 cases of IBD over a two-year period. The average age of the patients was 40 years with a standard deviation of 14. The gender ratio was male to female: 1.53. All patients underwent colonic biopsy. These 81 cases were distributed as follows based on the final clinical diagnosis: 19 cases of CD, 59 cases of UC, and 3 cases of IBD that clinicians were unable to classify. All these cases presented epithelial abnormalities on histology. When endoscopic and histopathological data were correlated: Among patients with UC, the endoscopic extent of the disease was histologically confirmed to be a homogeneous lesion(image 1), pancolitis, in 42 patients. Among CD patients, the heterogeneous nature of lesions(image 2) after histological study was found in 11 out of 19 CD patients (P = 0.009); the details of this correlation are documented in Fig. 1 . Histological architectural changes were more pronounced in UC than in CD. The details of these modifications are presented in Fig. 2 and image 3 (A et B). On the histological level, dysplastic foci were not observed in any of the cases. In UC, the inflammatory infiltrate predominates, as shown in Fig. 3 , especially cryptic abscesses (Fig. 3 and image 3 C) in 86% of cases (p = 0.02). Furthermore, in both diseases, there are coexisting architectural abnormalities and inflammatory infiltrates in particular basal plasmacytosis. Moreover, no granulomas were detected in the 19 cases of Crohn's disease. The extent and duration of the disease and the treatments administered to patients are recorded in Table 1 . The predictive values of heterogeneity in diagnosing UC in an IBD population have a sensitivity of 25% and a specificity of 42.1%. The positive predictive value (PPV) is 56%, and the negative predictive value (NPV) is 16%. Regarding the predictive values of heterogeneity in diagnosing Crohn's disease in an IBD population, there is a sensitivity of 57.9% and a specificity of 75%. The positive predictive value (PPV) is 44%, and the negative predictive value (NPV) is 84%. Image 1: Image of homogeneous lesion Image 2: Image of heterogeneous lesion Image 3 : HES (Haematoxicilin eosin saffron) x 200: A-B: Architectural abnormalities (bifurcation, cystization, dedifferentiated appearance of glands), C-Cryptic abscess and basal plasmacytosis. Table 1: Summary table of patient data on disease extent, follow-up duration, and treatments Discussion In Crohn's disease (CD), the homogeneous character of lesions was found in an the heterogeneous character of lesions was observed in approximately 58% of patients (11 out of 19). The presence of heterogeneity was also noted in both CD and UC. Our results indicate that the homogeneous character of lesions is strongly associated with UC, while the heterogeneous character is more common in CD. This would constitute a discriminating histological criterion for better classification of inflammatory bowel diseases (IBD) and is also explained by the continuous nature of lesions in endoscopy. These results are comparable to those in the literature. Thereby reinforcing the validity and reproducibility of our conclusions [ 5 ]. Histological evaluation of biopsy samples is crucial for establishing a specific diagnosis of IBD. This approach is essential for guiding therapeutic choices, taking into account significant differences in surgical treatment and long-term prognosis between UC and CD [ 8 ]. However, in about 10 to 20% of cases, it is difficult to make a clinical and histological distinction between UC and CD. In these situations, the diagnosis of Indeterminate Bowel Disease(IBD-U) is made, highlighting the complexity of diagnosing these diseases [ 8 ]. For the diagnosis of UC, the heterogeneity of lesions has a positive predictive value (PPV) of 56% and a relatively low negative predictive value (NPV) of 16%. For the diagnosis of CD, the heterogeneity of lesions shows a PPV of 44% and a higher NPV at 84%. Predictive values add an important dimension to understanding the clinical relevance of these histological features. This distinction can play an essential role in diagnostic and therapeutic decision-making, contributing to better management of patients with IBD. Most abnormal colonic mucosa biopsies do not provide a specific etiological diagnosis but rather show a pattern of lesion [ 5 ]. An important part of the diagnosis is the disease distribution pattern. Although UC is characterized by diffuse and continuous inflammation limited to the mucosa, discontinuous and focal forms can also be observed, emphasizing the complexity of the diagnosis [ 5 , 10 ]. There is no specific histological characteristic of UC that is not observed in CD, highlighting the need for a thorough clinical evaluation and contextual interpretation of histological results [ 5 , 9 , 10 ]. Epithelial abnormalities predominantly occur in UC, consistent with medical literature [ 8 , 11 ]. These abnormalities can be crucial in the diagnosis of IBD. Similarly, inflammatory infiltrate predominates in UC in our series. It is important to note that the presence of activity has no impact on disease categorization and has no diagnostic value as it can be observed in many forms of colitis. For example, cryptic abscesses can be observed in UC, CD, or infection [ 5 ]. Basal plasmacytosis is also a fairly constant and reproducible sign in the diagnosis of IBD [ 12 ]. In our series, basal plasmacytosis was present in both UC (76%) and CD (24%). No granulomas were detected in our series. Detecting granulomas in biopsies can be challenging due to their deep location within the intestinal wall, random sampling of biopsies, variability in granuloma presence among patients and disease stages, and the technique used for sample collection. It is crucial to carefully interpret histological findings and consider other diagnostic criteria, including clinical and radiological data, to achieve an accurate diagnosis and develop an appropriate treatment plan for patients with inflammatory bowel diseases. Differential diagnosis is important, especially during the initial onset of symptoms. Conditions to consider include ischemic colitis, occurring most often in the elderly, microscopic colitis (collagenous and lymphocytic) occurring preferentially in the young, drug-induced enterocolitis (especially non-steroidal anti-inflammatory drugs), radiation-induced digestive tract disorders, celiac disease, and its complications. Conclusion The homogeneous character of epithelial abnormalities is a discriminating histological criterion, with a predominant observation in ulcerative colitis (UC) compared to Crohn's disease (CD). This suggests that this characteristic can play an important role in the classification of chronic inflammatory bowel diseases (IBD). Most biopsies from patients with colitis do not present pathognomonic histological characteristics. It is crucial to interpret them considering clinical, endoscopic, and biological data to reach an accurate diagnosis. The histopathology report is based on the description of histological patterns rather than a definitive diagnosis. This report offers a preliminary differential diagnosis and provides the gastroenterologist other arguments for more accurate diagnosis. Declarations Ethics approval and consent to participate This retrospective study was conducted in accordance with the principles of the Declaration of Helsinki (2013 revision). Ethical approval was obtained from the Ethics Committee of the Centre Hospitalier Universitaire Hassan II de Fès (Ref: CE-CHUH2-2024-015; Date of approval: 15 March 2024). Due to the retrospective nature of the study and the use of fully anonymized patient data, the requirement for informed consent was waived by the Ethics Committee. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors received no specific funding for this work. Authors’ contributions SE, ME and SM designed the study LT, NH and LC supervised the work. HAB collected the data and wrote the manuscript. HB, ZM and FI analyzed the data. All authors reviewed and approved the final manuscript. Acknowledgements Not applicable. References Ondrej Fabian et Lukas Bajer. Histopathological Evaluation of Microscopic Activity in Inflammatory Bowel Diseases, World jounal of gastroenterology , 28th September 2022. 10.3748/wjg.v28.i36.5300 PMC9521520, PMID: 36185628. CROHN BB, OPPENHEIMER GINZBURGL. GD. Regional ileitis; a pathologic and clinical entity. Am J Med . 1952;13(5):583 – 90. 10.1016/0002-9343(52)90025-9 . PMID: 12996536. SCENIC. International Consensus Statement on Surveillance and Management of Dysplasia in IBD. Gastrointest Endosc . 2015;148(3):639–651.e28. 10.1053/j.gastro.2015.01.031 . PMID: 25702852. Rath I, Ahmed S, Biligi DS. (2020). Diagnostic Dilemma of Inflammatory Bowel Disease: A Study from a Tertiary Hospital in Southern India. Int J Sci Study, 8(3). Haboubi N. Reporting Colonic Biopsies in Patients With Inflammatory Bowel Disease; a Practical Approach. Inflamm Bowel Dis . 2019;25(4):679–684. 10.1093/ibd/izy288 . PMID: 30256953. Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? Clin Gastroenterol Hepatol . 2014;12(6):929 – 34.e2. 10.1016/j.cgh.2013.07.022 . Epub 2013 Aug 1. PMID: 23911875. Molander P, Sipponen T, Kemppainen H, Jussila A, Blomster T, Koskela R, Nissinen M, Rautiainen H, Kuisma J, Kolho KL, Färkkilä M. Achievement of Deep Remission during Scheduled Maintenance Therapy with TNFα-Blocking Agents in IBD. J Crohns Colitis. 2013;7:730–5. [PubMed] [Google Scholar]. Chbani L, Hammas N, El Fakir S, Nejjari C, Amarti A. Interobserver variability and value of histological examination in the diagnosis of inflammatory bowel disease (experience of Hassan II University Hospital Fez). J Africain d'Hépato-Gastroentérologie. 2012;6:288–91. Schumacher G, Kollberg B, Sandstedt B. A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Histologic course during the 1st year after presentation. Scand J Gastroenterol . 1994;29(4):318 – 32. 10.3109/00365529409094843 . PMID: 8047806. Odze. and Goldblum: Surgical Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas. 3rd ed. Philadelphia, PA: Saunders; 2014. enkins D, Balsitis M, Gallivan S, Dixon MF, Gilmour HM, Shepherd NA, Theodossi A, Williams GT. Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative. J Clin Pathol. 1997;50(2):93–105. PMID: 9155688; PMCID: PMC499731. Allison MC, Hamilton-Dutoit SJ, Dhillon AP, Pounder RE. (1987) The Value of Rectal Biopsy in Distinguishing Self-limited Colitis from Early Inflammatory Bowel Disease. QJ7Med 65: 985–95. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9304837","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":622214927,"identity":"24de4098-320e-4142-8933-6c10b6518536","order_by":0,"name":"Habsatou ABDOULAYE 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2","display":"","copyAsset":false,"role":"figure","size":82274,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant histological architectural changes in UC.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9304837/v1/0861e20ec4f5ce980c5ddbb2.png"},{"id":107243526,"identity":"c26e17f5-d2f3-45c0-b9d6-87a254752b84","added_by":"auto","created_at":"2026-04-19 07:52:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":64522,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of inflammatoire changes in both CD and UC\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9304837/v1/51b9638a43d683aae448bb9f.png"},{"id":107484668,"identity":"87051347-36dd-46ba-ab37-9eaa636bb29a","added_by":"auto","created_at":"2026-04-22 02:32:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":420870,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImage 1: Image of homogeneous lesion\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9304837/v1/c6bde9292a463a7afc9e214a.png"},{"id":107484376,"identity":"e83e3038-db82-4780-bfb3-c36433b40e32","added_by":"auto","created_at":"2026-04-22 02:31:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":316888,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImage 2: Image of heterogeneous lesion\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9304837/v1/fa6256d8bdd7d40927fc5968.png"},{"id":107243524,"identity":"edd9705b-eea5-4839-82ff-94f9b86e5825","added_by":"auto","created_at":"2026-04-19 07:52:29","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":578678,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImage 3:\u003c/strong\u003e HES (Haematoxicilin eosin saffron) x 200: A-B: Architectural abnormalities (bifurcation, cystization, dedifferentiated appearance of glands), C-Cryptic abscess and basal plasmacytosis.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9304837/v1/92350b50f8c5abaf3bc1b35d.png"},{"id":107487203,"identity":"fbe9a788-c7b3-4d06-822e-91affe631509","added_by":"auto","created_at":"2026-04-22 02:40:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1609308,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9304837/v1/51bfd7ad-b3d8-47cc-b9c6-cf9dc527a197.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive value of epithelial lesion heterogeneity in the etiological diagnosis of chronic inflammatory bowel disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInflammatory Bowel Diseases (IBD) are characterized by chronic, intermittent, or continuous inflammation of a portion of the digestive tract with an increased risk of dysplasia and colorectal cancer (CRC). They are relatively common, often starting between the ages of 15 and 30, and affecting both men and women equally. The first description of IBD dates back to 1932 when Burrill Bernard Crohn published his article \"Regional ileitis: A pathologic and clinical entity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistopathology plays a crucial role in the diagnosis, and histological examination is typically based on biopsy samples, which involve only the mucosa and the superficial part of the submucosa.\u003c/p\u003e \u003cp\u003eThe radiological signs of Crohn's disease include thickening of the intestinal wall, especially in the terminal ileum, ulcers, fistulas, and the presence of skip lesions (areas of intestinal lesions interspersed with healthy segments) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Histologically, this disease is characterized by discontinuous lesions, which may appear as affected segments with areas of healthy mucosa in between. Crohn's disease can affect any part of the gastrointestinal tract, from the mouth to the anus, and may also involve areas other than the colon, such as the terminal ileum. Histological features include transmural inflammation, spanning the entire intestinal wall, and the presence of granulomas, often located in the submucosa, making their detection difficult on superficial biopsies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUlcerative colitis (UC) is radiologically characterized by thickening of the colon and rectum walls, accompanied by ulcers and superficial wounds [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In UC, inflammation affects the rectocolonic mucosa continuously, without interruptions, and is generally limited to the colon and rectum, although it may start in the rectum and gradually spread to the colon. This condition is characterized by continuous and superficial inflammation of the colonic mucosa, without involvement of all layers of the intestinal wall. Unlike Crohn's disease, granulomas are not observed in UC, which is a significant distinction between the two conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn both subtypes of IBD, the infiltrate is primarily mononuclear, with a predominance of lymphocytes and plasma cells. The presence of neutrophils indicates an active disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe continuous development of colonoscopy technology has allowed clinicians to have a better view of the colon, providing pathologists with more material [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The diagnosis of IBD and other inflammatory conditions of the colon cannot be established when only one or a few features are present, given the lack of specific histological signs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Most abnormal biopsies of the colonic mucosa do not provide a specific etiological diagnosis but rather show a pattern of injury. An essential part of the diagnosis is the distribution pattern of the disease.\u003c/p\u003e \u003cp\u003eUlcerative Colitis (UC) is characterized by continuous, homogeneous lesions without any intervening healthy mucosa. On the other hand, focal lesions are more indicative of Crohn's disease (CD) but can also be observed in ischemic colitis and UC [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, normal endoscopic results do not necessarily reflect normal histology.\u003c/p\u003e \u003cp\u003eThe correlation between endoscopy and histology is weak, and up to one-third of patients with CD and ulcerative colitis in endoscopic remission may show signs of persistent histological activity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. An accurate assessment of microscopic disease activity using respective scoring indices is, therefore, necessary.\u003c/p\u003e \u003cp\u003eThe aim of our study is to correlate the final diagnosis based on clinical and endoscopic data with the heterogeneity of epithelial lesions in the etiological diagnosis of IBD. We also aim to evaluate the positive predictive value and negative predictive value of heterogeneity in diagnosing CD and UC.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis is a retrospective study involving 81 cases of IBD diagnosed at the Department of Pathological Anatomy and Cytology of Hassan II University Hospital in FES. The diagnosis was established based on fragments of endoscopic colonic biopsy fixed in 10% formalin, processed using conventional methods, and embedded in paraffin blocks. Sections of these blocks were stained with hematoxylin and eosin saffron (HES) following standard procedures.\u003c/p\u003e \u003cp\u003eThe inclusion criteria included an ileo-colonic biopsy, availability of endoscopic and clinical data, and the presence of sufficient histological criteria for diagnosis. Exclusion criteria were the unavailability of endoscopic data and insufficient histological criteria to confirm the diagnosis. Biopsies were obtained without orientation. Biopsied segments included the rectum in 23 cases, the ileocecal valve in 4 cases, and in 54 cases, the pathological colon without precise localization. In Crohn's disease, biopsies of the terminal ileum were performed in 4 cases. Slides were annotated by two experienced gastrointestinal pathologists.\u003c/p\u003e \u003cp\u003eAfter an initial histological study, a review of HES slides was conducted by a second experienced gastrointestinal pathologist to thoroughly analyze the various epithelial abnormalities and lesion heterogeneity.\u003c/p\u003e \u003cp\u003eThe heterogeneity of lesions was categorized into two groups: homogeneous or heterogeneous.\u003c/p\u003e \u003cp\u003eA degree of heterogeneity of lesions was observed within a single biopsy, which was classified into two groups: homogeneous and heterogeneous.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDefinition of terms:\u003c/h2\u003e \u003cp\u003eIn the context of inflammatory bowel diseases (IBD), lesion heterogeneity refers to the diversity of observed tissue alterations, including their location, type, depth, and histological appearance. This variability can have significant implications for the diagnosis, treatment, and prognosis of patients with these inflammatory intestinal conditions.\u003c/p\u003e \u003cp\u003eA lesion is considered homogeneous when the entire or the majority of the sample exhibits a uniform appearance upon examination. This means that the entirety or most of the examined area is abnormal. A lesion is termed heterogeneous when an irregular or varied appearance is present upon examination, indicating that a portion of the sample (or fragment) is entirely normal while another part is abnormal.\u003c/p\u003e \u003cp\u003eCorrelations were made between the presence of homogeneous or heterogeneous characteristics of the lesions and various epithelial abnormalities, as well as the clinical diagnosis of CD and UC. Positive and negative predictive values were also evaluated.\u003c/p\u003e \u003cp\u003eVarious epithelial abnormalities included architectural anomalies such as loss of crypt parallelism, bifurcation, branching, cystic change, atrophy, dedifferentiated gland appearance, as well as surface villi appearance and dysplastic lesions. The type of inflammatory infiltrate was also examined.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using SPSS software version 26, and a correlation was considered significant if p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The tests conducted included Pearson's chi-square test, Fischer's exact test, and the student's t-test (T-test).\u003c/p\u003e \u003cp\u003eDescriptive statistics such as mean, standard deviation, and percentages were calculated to characterize the studied sample. A Pearson correlation analysis was used to assess the presence of homogeneous or heterogeneous lesion characteristics with various epithelial anomalies and the clinical diagnosis of CD and UC. Fischer's t-test and the Student's t-test were used to compare epithelial anomalies between CD and UC.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOur study included 81 cases of IBD over a two-year period.\u003c/p\u003e\n\u003cp\u003eThe average age of the patients was 40 years with a standard deviation of 14. The gender ratio was male to female: 1.53.\u003c/p\u003e\n\u003cp\u003eAll patients underwent colonic biopsy.\u003c/p\u003e\n\u003cp\u003eThese 81 cases were distributed as follows based on the final clinical diagnosis: 19 cases of CD, 59 cases of UC, and 3 cases of IBD that clinicians were unable to classify. All these cases presented epithelial abnormalities on histology.\u003c/p\u003e\n\u003cp\u003eWhen endoscopic and histopathological data were correlated: Among patients with UC, the endoscopic extent of the disease was histologically confirmed to be a homogeneous lesion(image 1), pancolitis, in 42 patients. Among CD patients, the heterogeneous nature of lesions(image 2) after histological study was found in 11 out of 19 CD patients (P\u0026thinsp;=\u0026thinsp;0.009); the details of this correlation are documented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eHistological architectural changes were more pronounced in UC than in CD. The details of these modifications are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and image 3 (A et B).\u003c/p\u003e\n\u003cp\u003eOn the histological level, dysplastic foci were not observed in any of the cases. In UC, the inflammatory infiltrate predominates, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, especially cryptic abscesses (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and image 3 C) in 86% of cases (p\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e\n\u003cp\u003eFurthermore, in both diseases, there are coexisting architectural abnormalities and inflammatory infiltrates in particular basal plasmacytosis.\u003c/p\u003e\n\u003cp\u003eMoreover, no granulomas were detected in the 19 cases of Crohn\u0026apos;s disease.\u003c/p\u003e\n\u003cp\u003eThe extent and duration of the disease and the treatments administered to patients are recorded in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eThe predictive values of heterogeneity in diagnosing UC in an IBD population have a sensitivity of 25% and a specificity of 42.1%. The positive predictive value (PPV) is 56%, and the negative predictive value (NPV) is 16%.\u003c/p\u003e\n\u003cp\u003eRegarding the predictive values of heterogeneity in diagnosing Crohn\u0026apos;s disease in an IBD population, there is a sensitivity of 57.9% and a specificity of 75%. The positive predictive value (PPV) is 44%, and the negative predictive value (NPV) is 84%.\u003c/p\u003e\n\u003cp\u003eImage 1: Image of homogeneous lesion\u003c/p\u003e\n\u003cp\u003eImage 2: Image of heterogeneous lesion\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImage 3\u003c/strong\u003e: HES (Haematoxicilin eosin saffron) x 200: A-B: Architectural abnormalities (bifurcation, cystization, dedifferentiated appearance of glands), C-Cryptic abscess and basal plasmacytosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eSummary table of patient data on disease extent, follow-up duration, and treatments\u003cv:shapetype id=\"_x0000_t75\" coordsize=\"21600,21600\" o:spt=\"75\" o:preferrelative=\"t\" path=\"m@4@5l@4@11@9@11@9@5xe\" filled=\"f\" stroked=\"f\"\u003e\n \u003cv:stroke joinstyle=\"miter\"\u003e\n \u003cv:formulas\u003e\n \u003cv:f eqn=\"if lineDrawn pixelLineWidth 0\"\u003e\n \u003cv:f eqn=\"sum @0 1 0\"\u003e\n \u003cv:f eqn=\"sum 0 0 @1\"\u003e\n \u003cv:f eqn=\"prod @2 1 2\"\u003e\n \u003cv:f eqn=\"prod @3 21600 pixelWidth\"\u003e\n \u003cv:f eqn=\"prod @3 21600 pixelHeight\"\u003e\n \u003cv:f eqn=\"sum @0 0 1\"\u003e\n \u003cv:f eqn=\"prod @6 1 2\"\u003e\u0026nbsp;\u003cv:f eqn=\"prod @7 21600 pixelWidth\"\u003e\u0026nbsp;\u003cv:f eqn=\"sum @8 21600 0\"\u003e\u0026nbsp;\u003cv:f eqn=\"prod @7 21600 pixelHeight\"\u003e\u0026nbsp;\u003cv:f eqn=\"sum @10 21600 0\"\u003e\u0026nbsp;\u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:formulas\u003e\n \u003cv:path o:extrusionok=\"f\" gradientshapeok=\"t\" o:connecttype=\"rect\"\u003e\u0026nbsp;\u003c/v:path\u003e\n \u003c/v:stroke\u003e\n \u003c/v:shapetype\u003e\u003cimg src=\"https://myfiles.space/user_files/58893_b39df98f09c4a4bb/58893_custom_files/img1776257530.png\" alt=\"image\" width=\"541\" height=\"411\"\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn Crohn's disease (CD), the homogeneous character of lesions was found in an the heterogeneous character of lesions was observed in approximately 58% of patients (11 out of 19). The presence of heterogeneity was also noted in both CD and UC.\u003c/p\u003e \u003cp\u003eOur results indicate that the homogeneous character of lesions is strongly associated with UC, while the heterogeneous character is more common in CD. This would constitute a discriminating histological criterion for better classification of inflammatory bowel diseases (IBD) and is also explained by the continuous nature of lesions in endoscopy.\u003c/p\u003e \u003cp\u003eThese results are comparable to those in the literature. Thereby reinforcing the validity and reproducibility of our conclusions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistological evaluation of biopsy samples is crucial for establishing a specific diagnosis of IBD. This approach is essential for guiding therapeutic choices, taking into account significant differences in surgical treatment and long-term prognosis between UC and CD [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, in about 10 to 20% of cases, it is difficult to make a clinical and histological distinction between UC and CD. In these situations, the diagnosis of Indeterminate Bowel Disease(IBD-U) is made, highlighting the complexity of diagnosing these diseases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor the diagnosis of UC, the heterogeneity of lesions has a positive predictive value (PPV) of 56% and a relatively low negative predictive value (NPV) of 16%. For the diagnosis of CD, the heterogeneity of lesions shows a PPV of 44% and a higher NPV at 84%.\u003c/p\u003e \u003cp\u003ePredictive values add an important dimension to understanding the clinical relevance of these histological features. This distinction can play an essential role in diagnostic and therapeutic decision-making, contributing to better management of patients with IBD.\u003c/p\u003e \u003cp\u003eMost abnormal colonic mucosa biopsies do not provide a specific etiological diagnosis but rather show a pattern of lesion [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAn important part of the diagnosis is the disease distribution pattern. Although UC is characterized by diffuse and continuous inflammation limited to the mucosa, discontinuous and focal forms can also be observed, emphasizing the complexity of the diagnosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is no specific histological characteristic of UC that is not observed in CD, highlighting the need for a thorough clinical evaluation and contextual interpretation of histological results [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEpithelial abnormalities predominantly occur in UC, consistent with medical literature [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These abnormalities can be crucial in the diagnosis of IBD.\u003c/p\u003e \u003cp\u003eSimilarly, inflammatory infiltrate predominates in UC in our series. It is important to note that the presence of activity has no impact on disease categorization and has no diagnostic value as it can be observed in many forms of colitis. For example, cryptic abscesses can be observed in UC, CD, or infection [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Basal plasmacytosis is also a fairly constant and reproducible sign in the diagnosis of IBD [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our series, basal plasmacytosis was present in both UC (76%) and CD (24%).\u003c/p\u003e \u003cp\u003eNo granulomas were detected in our series. Detecting granulomas in biopsies can be challenging due to their deep location within the intestinal wall, random sampling of biopsies, variability in granuloma presence among patients and disease stages, and the technique used for sample collection. It is crucial to carefully interpret histological findings and consider other diagnostic criteria, including clinical and radiological data, to achieve an accurate diagnosis and develop an appropriate treatment plan for patients with inflammatory bowel diseases.\u003c/p\u003e \u003cp\u003eDifferential diagnosis is important, especially during the initial onset of symptoms. Conditions to consider include ischemic colitis, occurring most often in the elderly, microscopic colitis (collagenous and lymphocytic) occurring preferentially in the young, drug-induced enterocolitis (especially non-steroidal anti-inflammatory drugs), radiation-induced digestive tract disorders, celiac disease, and its complications.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe homogeneous character of epithelial abnormalities is a discriminating histological criterion, with a predominant observation in ulcerative colitis (UC) compared to Crohn's disease (CD). This suggests that this characteristic can play an important role in the classification of chronic inflammatory bowel diseases (IBD).\u003c/p\u003e \u003cp\u003eMost biopsies from patients with colitis do not present pathognomonic histological characteristics. It is crucial to interpret them considering clinical, endoscopic, and biological data to reach an accurate diagnosis.\u003c/p\u003e \u003cp\u003eThe histopathology report is based on the description of histological patterns rather than a definitive diagnosis. This report offers a preliminary differential diagnosis and provides the gastroenterologist other arguments for more accurate diagnosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was conducted in accordance with the principles of the Declaration of Helsinki (2013 revision). Ethical approval was obtained from the Ethics Committee of the Centre Hospitalier Universitaire Hassan II de F\u0026egrave;s (Ref: CE-CHUH2-2024-015; Date of approval: 15 March 2024).\u003c/p\u003e\n\u003cp\u003eDue to the retrospective nature of the study and the use of fully anonymized patient data, the requirement for informed consent was waived by the Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSE, ME and SM designed the study\u003c/p\u003e\n\u003cp\u003eLT, NH and LC supervised the work.\u003c/p\u003e\n\u003cp\u003eHAB collected the data and wrote the manuscript.\u003c/p\u003e\n\u003cp\u003eHB, ZM and FI analyzed the data.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOndrej Fabian et Lukas Bajer. Histopathological Evaluation of Microscopic Activity in Inflammatory Bowel Diseases, \u003cem\u003eWorld jounal of gastroenterology\u003c/em\u003e, 28th September 2022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3748/wjg.v28.i36.5300\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v28.i36.5300\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e PMC9521520, PMID: 36185628.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCROHN BB, OPPENHEIMER GINZBURGL. GD. Regional ileitis; a pathologic and clinical entity. \u003cem\u003eAm J Med\u003c/em\u003e. 1952;13(5):583\u0026thinsp;\u0026ndash;\u0026thinsp;90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0002-9343(52)90025-9\u003c/span\u003e\u003cspan address=\"10.1016/0002-9343(52)90025-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 12996536.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSCENIC. International Consensus Statement on Surveillance and Management of Dysplasia in IBD. \u003cem\u003eGastrointest Endosc\u003c/em\u003e. 2015;148(3):639\u0026ndash;651.e28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.gastro.2015.01.031\u003c/span\u003e\u003cspan address=\"10.1053/j.gastro.2015.01.031\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 25702852.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRath I, Ahmed S, Biligi DS. (2020). Diagnostic Dilemma of Inflammatory Bowel Disease: A Study from a Tertiary Hospital in Southern India. Int J Sci Study, 8(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaboubi N. Reporting Colonic Biopsies in Patients With Inflammatory Bowel Disease; a Practical Approach. \u003cem\u003eInflamm Bowel Dis\u003c/em\u003e. 2019;25(4):679\u0026ndash;684. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ibd/izy288\u003c/span\u003e\u003cspan address=\"10.1093/ibd/izy288\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 30256953.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? \u003cem\u003eClin Gastroenterol Hepatol\u003c/em\u003e. 2014;12(6):929\u0026thinsp;\u0026ndash;\u0026thinsp;34.e2. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cgh.2013.07.022\u003c/span\u003e\u003cspan address=\"10.1016/j.cgh.2013.07.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2013 Aug 1. PMID: 23911875.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMolander P, Sipponen T, Kemppainen H, Jussila A, Blomster T, Koskela R, Nissinen M, Rautiainen H, Kuisma J, Kolho KL, F\u0026auml;rkkil\u0026auml; M. Achievement of Deep Remission during Scheduled Maintenance Therapy with TNFα-Blocking Agents in IBD. J Crohns Colitis. 2013;7:730\u0026ndash;5. [PubMed] [Google Scholar].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChbani L, Hammas N, El Fakir S, Nejjari C, Amarti A. Interobserver variability and value of histological examination in the diagnosis of inflammatory bowel disease (experience of Hassan II University Hospital Fez). J Africain d'H\u0026eacute;pato-Gastroent\u0026eacute;rologie. 2012;6:288\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchumacher G, Kollberg B, Sandstedt B. A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Histologic course during the 1st year after presentation. \u003cem\u003eScand J Gastroenterol\u003c/em\u003e. 1994;29(4):318\u0026thinsp;\u0026ndash;\u0026thinsp;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/00365529409094843\u003c/span\u003e\u003cspan address=\"10.3109/00365529409094843\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 8047806.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOdze. and Goldblum: Surgical Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas. 3rd ed. Philadelphia, PA: Saunders; 2014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eenkins D, Balsitis M, Gallivan S, Dixon MF, Gilmour HM, Shepherd NA, Theodossi A, Williams GT. Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative. J Clin Pathol. 1997;50(2):93\u0026ndash;105. PMID: 9155688; PMCID: PMC499731.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllison MC, Hamilton-Dutoit SJ, Dhillon AP, Pounder RE. (1987) The Value of Rectal Biopsy in Distinguishing Self-limited Colitis from Early Inflammatory Bowel Disease. QJ7Med 65: 985\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Crohn's disease, Ulcerative Colitis, Predictive Value, Heterogeneity","lastPublishedDoi":"10.21203/rs.3.rs-9304837/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9304837/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eIntroduction\u003c/b\u003e: Chronic inflammatory bowel diseases (IBD) are characterized by chronic, intermittent, and continuous inflammation of a part of the digestive tract, with an increased risk of dysplasia and colorectal cancer (CRC). They typically include Crohn's disease (CD) and ulcerative colitis (UC). The diagnosis of IBD is multidisciplinary. One biopsies are essential for establishing a diagnosis, monitoring treatment, and/or identifying complications. This study evaluates the predictive value of the heterogeneity of epithelial abnormalities in the etiological diagnosis of IBD.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMaterials and Methods\u003c/b\u003e: This is a retrospective study involving 81 cases of IBD diagnosed at the Department of Pathological Anatomy and Cytology of the Hassan II University Hospital in FES from 2021 to 2023. The diagnosis was established after histological examination. The homogeneous or heterogeneous nature of the lesions between differents biopsy sample was categorized into two groups.\u003c/p\u003e \u003cp\u003eCorrelations were made between the presence of homogeneous or heterogeneous characteristics of the lesions and the various epithelial abnormalities, as well as the clinical diagnosis of CD and UC. The positive and negative predictive values were assessed.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e: Our study included 81 cases of IBD. The average age of the patients was 40 years with a standard deviation of 14. All patients underwent colonic biopsy. These 81 cases were distributed as follows based on the final clinical diagnosis: 19 cases of CD, 59 cases of UC, and 3 cases of IBD on histological examination. When endoscopic and histopathological data were correlated, heterogeneous lesions were found in 44% of patients with CD compared to 16% with homogeneous characteristics. In UC, homogeneous lesions were found in 84% of patients compared to 56% with heterogeneous characteristics (P\u0026thinsp;=\u0026thinsp;0.009).\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion\u003c/b\u003e: Our study demonstrated that the homogeneous nature of epithelial abnormalities was more commonly observed in UC than in Crohn's disease. This could serve as a discriminatory histological criterion for better categorizing IBD.\u003c/p\u003e","manuscriptTitle":"Predictive value of epithelial lesion heterogeneity in the etiological diagnosis of chronic inflammatory bowel disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 07:52:24","doi":"10.21203/rs.3.rs-9304837/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-12T20:11:36+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"62462630003523549531427897286280449791","date":"2026-05-12T17:13:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T15:51:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"210215875347662369737709694323695287296","date":"2026-04-28T14:16:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-27T18:56:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"241800224074306350837161908878138991270","date":"2026-04-23T17:13:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"334658038430811656071414236841289821426","date":"2026-04-18T15:11:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-08T10:29:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-08T10:27:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-08T09:47:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-07T19:48:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2026-04-07T16:17:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c28a04a6-7b70-4d69-b2e5-c47aaca8fdc1","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-12T20:11:36+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"62462630003523549531427897286280449791","date":"2026-05-12T17:13:17+00:00","index":98,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T15:51:18+00:00","index":81,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T20:24:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 07:52:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9304837","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9304837","identity":"rs-9304837","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}