HISTOPATHOLOGICAL STUDY OF CHRONIC GASTRITIS · HISTOPATHOLOGICAL STUDY OF CHRONIC GASTRITIS Thesis...

HISTOPATHOLOGICAL STUDY OF CHRONIC GASTRITIS

Thesis submitted in partial fulfillment ofM.Sc. Degree in Pathology

By

Somaia AbduLatif Mahmoud Soliman M.B.B.Ch

Faculty of Medicine, Cairo University

Supervised by

Prof. Dr. Dalal Anwar ElwiProfessor of pathology

Faculty of MedicineCairo University

Ass. Prof. Dr. Mostafa Mohamed Salem

Assistant Professor of pathologyFaculty of medicine

Cairo University

Dr. Ahmed Abd- El Monem SolimanLecturer of PathologyFaculty of Medicine

Cairo University

Faculty of Medicine Cairo University

2012

الرحمن الرحیمهللابسم

أخرجك ھاتكم ـوهللا م من بطون أممع ـعل لك ـشیئا وج ال تعلمون م الس

.واألبصار واألفئدة لعلكم تشكرون

العظیم هللاصدق

)٧٨:النحل(

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. MostafaMohammed 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

Contents

Introduction & Aim of the work 1Review 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 58Results 60Discussion 86Summary 93Conclusion & Recommendation 95References 96Arabic summary

List of Abbreviation

Acquired immuno deficiency syndromeAIDS1

Autoimmune gastritisAG2

Campylobacter like organism testCLO test3

Chronic antral gastritisCAG4

CytomegalovirusCMV5

Diffuse antral gastritisDAG6

Enterochromaffin-like cellsECL cells7

Enzyme linked immunosorbent assaysELISA8

Gastric antral vascular ectasiaGAVE9

Gastrin cellsG cells10

Gastrointestinal tractGIT11

Graft versus host diseaseGVHD12

Helicobacter heilmanniiH. heilmannii 13

Helicobacter pyloriH.pylori14

Hematoxylin & eosinH & E15

Human immuno deficiency virusHIV16

Intraepithelial lymphocytesIELs17

Mucosa associated lymphoid tissueMALT18

Multifocal atrophic gastritisMAG 19

Non steroidal anti-inflammatory drugsNSAIDs20

Polymerase chain reactionPCR21

ProstaglandingsPG122

Proton pump inhibitorsPPIs23

Ptoral hypertensive gastropathyPHG24

Vacuolating cytotoxin AVacA25

List of Tables

page Table

11 Sydney System Classification of Chronic

Gastritis

Table (1)

60Sydney classification systemTable (2)

61 Frequency of various histological subtypesTable (3)

62 Age frequency in chronic gastritis casesTable (4)

63 Sex distribution in the studied casesTable (5)

64 Clinical presenting symptomsTable (6)

65 Frquency of various endoscopic picturesTable (7)

66 Categorization of H.pylori subtypesTable (8)

67 Classification of intensity of inflammation in

H.pylori associated cases

Table (9)

68 Classification according to activity in

H.pylori cases

Table (10)

69 Complications in H.pylori associated casesTable (11)

70 Correlation between histological type & ageTable (12)

70 Correlation between Sex & histological typeTable (13)

71 Correlation between clinical presentation &

histological type

Table (14)


histological type

Table (15)


histological type

Table (15)

72 Correlation between endoscopic picture &

histological type

Table (16)


histological type

Table (17)


histological type

Table (18)

74 Corrlation between endoscopic picture &

histological type

Table (19)


subtypes of H.pylori positive group

Table (20 )



Table (21)



Table (22 )



Table (23)



Table (24)

List of Figures

PageFigure

8Diagram of 4 anatomical & 3 histological

areas of the stomach

Figure(1)

14Diagram of H.pylori structure.Figure(2)

76Chronic superficial gastritis (gastric mucosal

glands showing colonization by H.pylori

organisms). (H&E x400)

Figure (3)



organisms). (H&E x400)

Figure (4)



organisms). (Giemsa stain x400)

Figure (5)



organisms) (Giemsa stain x400)

Figure (6)



organisms) (Giemsa stain x400)

Figure (7)

78Follicullar gastritis, H.pylori associated, showing

lymphoid follicle situated deep in the antral

mucosa. (H&E x100)

Figure (8)

79Chronic atrophic gastritis, showing marked

decrease in number of gastric mucosal glands.

(H&E x100)

Figure (9)

79chronic gastritis, showing intestinal metaplasia.

(H&E x100)

Figure (10)

80Lymphocytic gastritis, showing lymphocytic

infiltration of the lamina propria & intraepithelial

lymphocytosis. (H&E x250)

Figure (11)

80Esinophilic gastritis, showing that the lamina

propria is infiltrated by a large number of

esinophils. (H&E x250)

Figure (12)

81Esinophilic gastritis, showing marked infiltration

of the lamina propria by esinophils. (H&E

x250)

Figure (13)

81Esinophilic gastritis, showing invasion of

mucosal glands by esinophils (diagnostic

criteria). (H&E x400)

Figure (14)

82Reactive gastropathy, showing the foveolar

hyperplasia & torsuosity. (H&E x100)

Figure (15)

82Reactive gastropathy, showing smooth muscles

reaching near the mucosal surface & sparse

inflammatory infiltrate. (H&E x250)

Figure (16)

83Autoimmune gastritis, showing atrophy of

oxyntic mucosal glands. (H&E x100)

Figure (17)


oxyntic mucosal glands & its replacement by

intestinal type cells (intestinal metaplasia).

(H&E x250)

Figure (18)




(H&E x250)

Figure (19)




(H&E x250)

Figure (20)

85chronic gastritis in a patient recieved

radiotherapy, showing glandular mucosal

degenerative changes. (H&E x250)

Figure (21)

List of Graphs

pageGraph

60Frequency of various histological subtypesGraph (1)

61Age frequency in chronic gastritis casesGraph (2)

62Sex distribution in the studied casesGraph (3)

63Clinical presenting symptomsGraph (4)

64Frquency of various endoscopic picturesGraph (5)

65Categorization of H.pylori subtypesGraph (6)

66Classification of intensity of inflammation in

H.pylori associated cases

Graph (7)

67Classification according to activity in H.pylori

cases

Graph (8)

68Complications in H.pylori associated casesGraph (9)

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 2010. 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

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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, 2007.

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).


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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).


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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).


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AIM OF THE WORK

Histopathological revision of all available archival material of chronic

gastritis in the last 2 years (2009-2010), 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.

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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.


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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).


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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).


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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.

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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 long-

standing 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

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