HISTOPATHOLOGICAL STUDY OF CHRONIC GASTRITIS

Transcription

1 HISTOPATHOLOGICAL STUDY OF CHRONIC GASTRITIS Thesis submitted in partial fulfillment of M.Sc. Degree in Pathology By Somaia AbduLatif Mahmoud Soliman M.B.B.Ch Faculty of Medicine, Cairo University Supervised by Prof. Dr. Dalal Anwar Elwi Professor of pathology Faculty of Medicine Cairo University Ass. Prof. Dr. Mostafa Mohamed Salem Assistant Professor of pathology Faculty of medicine Cairo University Dr. Ahmed Abd- El Monem Soliman Lecturer of Pathology Faculty of Medicine Cairo University Faculty of Medicine Cairo University 2012

2 الله بسم الرحمن الرحیم و الله أ خ ر ج ك م م ن ب ط ون أ مھ ات ك م لا ت ع ل م ون ش ی ي ا و جع ل ل كم ال سم ع و الا ب ص ار و الا ف ي د ة ل ع ل ك م ت ش ك ر ون. العظیم الله صدق (النحل: ٧٨ )

3 Acknowledgement First and foremost "Thanks to God", the most merciful and kind. I am honored to have Prof. Dr. Dalal Anwar Elwi, Professor of Pathology, Faculty of Medicine, Cairo University, as a supervisor of this work. I am deeply grateful and most appreciative to her great efforts, kind guidance and valuable advice that encouraged and helped me to finish this work. My profound gratitude goes to Prof. Dr. Mostafa Mohammed Samy Salem assistant Professor of Pathology, Faculty of Medicine, Cairo University for his close supervision and precious remarks throughout the course of this study. Special thanks are owed to Dr. Ahmed Abd- Elmonem Soliman, lecturer of Pathology, Faculty of medicine, Cairo University, who saved no time and effort in helping me, his constant support, continuous encouragement and constructive comments allowed me to accomplish this work. Finally, I would like to thank my family for their patience, love, motivation and support throughout this work. Somia AbduLatif

4 Contents Introduction & Aim of the work 1 Review of literature: Structure of the stomach 5 Classification 9 Chronic gastritis associated with Helicobacter pylori infection 13 Autoimmune gastritis 26 Reactive gastropathy 32 Radiation gastritis 35 Lymphocytic gastritis 36 Granulomtous gastritis 38 Esinophilic gastritis 43 Other causes of infectious gastritis 46 Vascular gastropathy 51 Collagenous gastritis 54 Ureamic gastropathy 56 Graft Versus Host Disease 57 Materials & Methods 58 Results 60 Discussion 86 Summary 93 Conclusion & Recommendation 95 References 96 Arabic summary

5 List of Abbreviation AIDS AG CLO test CAG CMV DAG ECL cells ELISA GAVE G cells GIT GVHD H. heilmannii H.pylori H & E HIV IELs MALT MAG NSAIDs PCR PG1 PPIs PHG VacA Acquired immuno deficiency syndrome Autoimmune gastritis Campylobacter like organism test Chronic antral gastritis Cytomegalovirus Diffuse antral gastritis Enterochromaffin-like cells Enzyme linked immunosorbent assays Gastric antral vascular ectasia Gastrin cells Gastrointestinal tract Graft versus host disease Helicobacter heilmannii Helicobacter pylori Hematoxylin & eosin Human immuno deficiency virus Intraepithelial lymphocytes Mucosa associated lymphoid tissue Multifocal atrophic gastritis Non steroidal anti-inflammatory drugs Polymerase chain reaction Prostaglandings Proton pump inhibitors Ptoral hypertensive gastropathy Vacuolating cytotoxin A

6 Table (1) Table (2) Table (3) Table (4) Table (5) Table (6) Table (7) Table (8) Table (9) Table (10) Table (11) Table (12) Table (13) Table (14) Table (15) List of Tables Table Sydney System Classification of Chronic Gastritis Sydney classification system Frequency of various histological subtypes Age frequency in chronic gastritis cases Sex distribution in the studied cases Clinical presenting symptoms Frquency of various endoscopic pictures Categorization of H.pylori subtypes Classification of intensity of inflammation in H.pylori associated cases Classification according to activity in H.pylori cases Complications in H.pylori associated cases Correlation between histological type & age Correlation between Sex & histological type Correlation between clinical presentation & histological type Correlation between clinical presentation & histological type page

7 Table (15) Table (16) Table (17) Table (18) Table (19) Table (20 ) Table (21) Table (22 ) Table (23) Table (24) Correlation between clinical presentation & histological type Correlation between endoscopic picture & histological type Correlation between endoscopic picture & histological type Correlation between endoscopic picture & histological type Corrlation between endoscopic picture & histological type Correlation between endoscopic picture & subtypes of H.pylori positive group Correlation between endoscopic picture & subtypes of H.pylori positive group Correlation between endoscopic picture & subtypes of H.pylori positive group Correlation between endoscopic picture & subtypes of H.pylori positive group Correlation between endoscopic picture & subtypes of H.pylori positive group

8 Figure(1) Figure(2) Figure (3) Figure (4) Figure (5) Figure (6) Figure (7) Figure (8) Figure (9) Figure (10) Figure (11) List of Figures Figure Diagram of 4 anatomical & 3 histological areas of the stomach Diagram of H.pylori structure. Chronic superficial gastritis (gastric mucosal glands showing colonization by H.pylori organisms). (H&E x400) Chronic superficial gastritis (gastric mucosal glands showing colonization by H.pylori organisms). (H&E x400) Chronic superficial gastritis (gastric mucosal glands showing colonization by H.pylori organisms). (Giemsa stain x400) Chronic superficial gastritis (gastric mucosal glands showing colonization by H.pylori organisms) (Giemsa stain x400) Chronic superficial gastritis (gastric mucosal glands showing colonization by H.pylori organisms) (Giemsa stain x400) Follicullar gastritis, H.pylori associated, showing lymphoid follicle situated deep in the antral mucosa. (H&E x100) Chronic atrophic gastritis, showing marked decrease in number of gastric mucosal glands. (H&E x100) chronic gastritis, showing intestinal metaplasia. (H&E x100) Lymphocytic gastritis, showing lymphocytic infiltration of the lamina propria & intraepithelial lymphocytosis. (H&E x250) Page

9 Figure (12) Figure (13) Figure (14) Figure (15) Figure (16) Figure (17) Figure (18) Figure (19) Figure (20) Figure (21) Esinophilic gastritis, showing that the lamina propria is infiltrated by a large number of esinophils. (H&E x250) Esinophilic gastritis, showing marked infiltration of the lamina propria by esinophils. (H&E x250) Esinophilic gastritis, showing invasion of mucosal glands by esinophils (diagnostic criteria). (H&E x400) Reactive gastropathy, showing the foveolar hyperplasia & torsuosity. (H&E x100) Reactive gastropathy, showing smooth muscles reaching near the mucosal surface & sparse inflammatory infiltrate. (H&E x250) Autoimmune gastritis, showing atrophy of oxyntic mucosal glands. (H&E x100) Autoimmune gastritis, showing atrophy of oxyntic mucosal glands & its replacement by intestinal type cells (intestinal metaplasia). (H&E x250) Autoimmune gastritis, showing atrophy of oxyntic mucosal glands & its replacement by intestinal type cells (intestinal metaplasia). (H&E x250) Autoimmune gastritis, showing atrophy of oxyntic mucosal glands & its replacement by intestinal type cells (intestinal metaplasia). (H&E x250) chronic gastritis in a patient recieved radiotherapy, showing glandular mucosal degenerative changes. (H&E x250)

10 List of Graphs Graph (1) Graph (2) Graph (3) Graph (4) Graph (5) Graph (6) Graph (7) Graph (8) Graph (9) Graph Frequency of various histological subtypes Age frequency in chronic gastritis cases Sex distribution in the studied cases Clinical presenting symptoms Frquency of various endoscopic pictures Categorization of H.pylori subtypes Classification of intensity of inflammation in H.pylori associated cases Classification according to activity in H.pylori cases Complications in H.pylori associated cases page

11 ABSTRACT Aim of Work: Analysis of chronic gastritis cases in 2 years duration, to detect rate of occurrence of different histological types, to reclassify cases according to the latest grading and staging systems and to compare the clinico-pathological features among Egyptian patients included in the study with registries of other countries. Methods: This was a retrospective study conducted at the Department of Pathology, Kasr Al Aini Hospital, Cairo University between January 2009 and December Analysis of 224 gastric biopsy specimens was done. We routinely make Hematoxylin/Eosin stained slides and perform Giemsa stain to check for H. pylori on all endoscopic gastric biopsies. Results: Out of two hundred & twenty four cases, H.pylori was found in 68.7% of the cases. Increased frequency of chronic gastritis was seen between 51 & 60 years. The most common clinical presentation was epigastric pain. The most common endoscopic finding was gastritis. The mean age of patients was 42 years and the age of patients ranged from 2.5 to 80 years. Females constituted 52% of cases while males were 48%. The mean age of female patients 41 years was less than that of male patients 43.4 years. Recommendations: For proper assessment of distribution of gastritis, multiple biopsies (at least five) from antrum, corpus & incisura angularis are important. Key Words: Chronic gastritis, Helicobacter pylori, lymphoid follicles. Baaed Study of Helicobacter Pylori in Egypt

12 Introduction & aim of the work Introduction The incidence and natural history of chronic gastritis has been greatly clarified by the systematic use of endoscopic gastric biopsy (Wyatt et al., 2001). Chronic gastritis is a histopathologic entity characterized by chronic inflammation of the stomach mucosa. Gastritis can be classified based on the underlying etiologic agent (e.g, Helicobacter pylori, bile reflux, nonsteroidal anti-inflammatory drugs [NSAIDs], autoimmunity, allergic response) and the histopathologic pattern, which may suggest the etiologic agent and clinical course (e.g, H. pylori associated multifocal atrophic gastritis) (Merck, Retrieved 2009). Although minimal inflammation is observed in some gastropathies, such as those associated with NSAID intake, these entities are frequently included in the differential diagnosis of chronic gastritis. Chemical or reactive gastritis is caused by injury of the gastric mucosa by reflux of bile and pancreatic secretions into the stomach, but it can also be caused by exogenous substances, including NSAIDs, acetylsalicylic acid, chemotherapeutic agents, and alcohol. These chemicals cause epithelial damage, erosions, and ulcers that are followed by regenerative hyperplasia detectable as foveolar hyperplasia, and damage to capillaries, with mucosal edema, hemorrhage, and increased smooth muscle in the lamina propria. Inflammation in these lesions caused by chemicals is minimal or lacking; therefore, the term gastropathy or chemical gastropathy is more appropriate to describe these lesions than is the term chemical or reactive gastritis as proposed by the updated Sydney classification of gastritis (Gao et al., 2009). -1-

13 Introduction & aim of the work No single classification of gastritis provides an entirely satisfactory description of all types of gastritis. However, an etiologic classification provides a direct target toward which therapy can be directed (Sepulveda et al., 2008). Infectious gastritis: Chronic gastritis caused by H. pylori infection. This is the most common cause of chronic gastritis. The most important advance in the field of chronic gastritis & other gastric diseases (peptic ulcer, carcinoma & malignant lymphoma) has been the awareness of the crucial role played by H.pylori (Wu et al., 2001). Infection by Helicobacter heilmannii, granulomatous gastritis associated with gastric infections in mycobacteriosis, syphilis, histoplasmosis, mucormycosis, South American blastomycosis, anisakiasis, or anisakidosis. Chronic gastritis associated with parasitic infections such as Strongyloides species, schistosomiasis, Diphyllobothrium latum. Viral infections such as CMV and herpes virus infection (Hasegawa et al., 2009). Noninfectious gastritis: autoimmune gastritis, chemical gastropathy, usually related to chronic bile reflux or NSAID and aspirin intake, Uremic gastropathy (Siegelbaum et al, 2006). chronic noninfectious granulomatous gastritis, associated with the following: Crohn disease, Sarcoidosis, Wegener granulomatosis, Foreign bodies, Cocaine use, Isolated granulomatous gastritis, Chronic granulomatous disease of childhood, eosinophilic granuloma, allergic granulomatosis and vasculitis, plasma cell granulomas, rheumatoid nodules, tumoral amyloidosis and granulomas associated with gastric carcinoma, gastric lymphoma, Langerhans cell histiocytosis (Maeng et al., 2004). Eosinophilic gastritis, radiation injury to the stomach, GVHD, ischemic gastritis, gastritis secondary to drug therapy (Quentin et al., 2006). Lymphocytic gastritis, including gastritis associated with celiac disease (also called collagenous gastritis) (Leung et al., 2009). -2-

14 Introduction & aim of the work Cases of histologically documented chronic gastritis are diagnosed as chronic gastritis of undetermined etiology or gastritis of undetermined type when none of the findings reflect any of the described patterns of gastritis and a specific cause cannot be identified (Galiatsatos et al., 2009). -3-

15 Introduction & aim of the work AIM OF THE WORK Histopathological revision of all available archival material of chronic gastritis in the last 2 years ( ), collected from the pathology department, Faculty of medicine, Cairo University Hospital, then statistical evaluation and correlation between age, clinical data, endoscopy or any relevant data available in the request sheets and the histopathological findings. Assessment of histopathological types, their incidence, & complications in order to have better treatment chances. -4-

16 Review of literature Structure of the stomach *Anatomy: Anatomically, the stomach is divided into four regions: Cardia: It is a narrow portion immediately distal to gastro-esophageal junction. Fundus: It is gastric portion that extends above the level of gastro-esophageal junction. Body (corpus): It is the part that extends proximal to incisura angularis (angle along the lesser curvature). Antrum: It is the part that extends distal to incisura angularis. (Owen, 1986) * Histology: I- The Mucosa: The normal gastric mucosa consists of epithelium, delicate stroma of connective tissue (lamina propria) and muscularis mucosa. The epithelium: It has as distinct glandular compartments, superficial zone, neck zone and deep zone. The superficial glandular zone: Composed of straight, narrow, tubular pits (foveolae) lined by surface mucous cells and neck mucous cells. They remain the same through out the stomach. -5-

17 Review of literature The surface mucous cells: tall columnar with basal nuclei and clear luminal cytoplasm due to accumulation of large mucin vacuoles towards the luminal surface. The neck mucous cells: smaller because they are compressed and distorted by adjacent cells. They have basal nucleus and finely granular cytoplasm due to presence of small mucin vacuoles smaller than those in the surface mucous cells distributed throughout the cytoplasm. The deep zone: is composed of glands which their bases lies close to or in the muscularis mucosa and their upper ends open into the bases of the superficial zone pits. It has variable composition throughout the different gastric histological patterns. The neck zone or the isthmus: it lies between superficial and deep zone. It is lined by immature stem cells mixed with some neck mucous cells. The stem cells proliferate and migrate upward after differentiation to replace the mucous cells of the superficial zone and downward to replace the various cell types in the deep zone glands (Stevens and Lowe, 1997). There are three main histological patterns which delineate the main areas of the stomach: the cardia, the fundus or the pylorus (Lewin et al., 1992). The cardiac mucosa: The superficial and deep zones are of about equal thickness. The deep zone is composed of tubular and branched glands; some of them are complex and coiled. They are lined by mucous cells, few acid producing cells and scattered endocrine cells. The cardiac glands are quite similar to pyloric glands but more coiled and dilated (Helander et al., 1986). -6-

18 Review of literature The body (fundic) glands: The superficial zone accounts 25% or less of the mucosal thickness. The deep zone is composed of tightly packed long straight tubular glands, 5-15mm long, and end blindly at the muscularis mucosa. They are lined by acid producing cells (parietal or oxyntic cells), enzyme producing cells (chief or peptic or zymogen cells), neck mucous cells and scattered endocrine cells (Owen, 1997). The pyloric (antral) glands: The superficial zone occupies slightly more than 50% of the mucosal thickness and the crypts are often branched. The deep zone is composed of tortuous or branched glands. They are lined by mucous cells, scattered acid producing cells and numerous endocrine cells. The acid producing cells become more numerous close to the pyloric spincter (Helander et al., 1986). The lamina propria: It is fibroreticular connective tissue that is situated between the surface epithelium and muscularis mucosa, forming the stroma in between the glands. It contains fine capillary plexus, nonmyelinated nerves, some fibroblasts, occasional smooth muscle cells passing from the muscularis mucosa and rare plasma cells (Owen, 1997). The muscularis mucosa: It consists of poorly defined layer of smooth muscle fibers (Owen, 1997). II- The Submucosa: Consists of loose connective tissue that supports the large blood vessels, lymphatics and the Miessner s plexus of nerves. It also contains small collection of fat cells and some esinophils (Lawson, 1988). -7-

19 Review of literature III- The Muscularis Propria: The muscular wall of the stomach differes from the standard digestive pattern by the presence of third layer of oblique muscle fibers (inner oblique) which is absent in the pyloric region (Owen, 1986). IV- The Serosa: It consists of thin layer of connective tissue covered by a layer of flat mesothelial cells (Owen, 1986). Figure (1): Diagram of 4 anatomical & 3 histological areas of the stomach. -8-

20 Review of literature Classification of chronic gastritis Chronic gastritis represents the non-specific histopathological sequelae to diffuse long-standing and multifactorial injury to the gastric mucosa. In a longstanding condition, histological appearances change with time and similar histological appearances may result from differing etiologies, Whitehead et al., advocate classification of chronic gastritis according to mucosal type, the grade of gastritis, whether it is superficial or atrophic, and the type of associated metaplasia (Whitehead et al., 1972). Strickland, & Mackay, 1973 identified type A and type B chronic gastritis based on topography. Type A refers to chronic atrophic gastritis involving the corpus and often associated with parietal cell autoantibodies and minimal antral involvement. Type B gastritis involves the distal stomach predominantly with only patchy involvement of the corpus. This is not associated with parietal cell autoantibodies and is considerably more prevalent than type A. This classification has been widely adopted and continues to be used. The discovery of H. pylori and its association with chronic gastritis has cast new light on the condition, Wyatt, & Dixon, 1988 proposed a classification based on histological features and pathogenesis. This consisted of type A (autoimmune), type B (bacterial), and reflux or chemical gastritis. The most widely used classification of chronic gastritis is the Sydney system which was devised by an international Working Party of experts and attempts to draw many previous classifications together (Price. 1991). This system combines etiology, topography and morphology. The system relies on at least two mucosal biopsies from both the antrum and the corpus, in -9-