Turk J Gastroenterol 2014; 25: 233-47

What is ? What is gastropathy? How is it classified? Serra Kayaçetin, Servet Güreşçi Review Department of , Ankara Numune Education and Training Hospital, Ankara, Turkey

ABSTRACT Stomach endoscopic are made to determine the diagnosis of the illness, its stage, and follow-up after the treatment. It is very significant to collaborate with the clinician while evaluating endoscopic biopsies. Besides the clinical and laboratory information of the patient, the endoscopic appearance of the lesion should be known. The clinician and pathologist should use the same language and the same terminology. Although new classifications have been made to prevent the confusion of terminologies in neoplastic processes recently, most centers around the world have reported non-invasive neoplasias without giving any certain diagnosis by just commenting on it. The clinician should understand what the pathologist wants to say; pathologists should know the approach of the clinician (repetition of the , endoscopic resection, surgery). There is Helicobacter pylori (HP) in most of the stomach as the etiologic agent. No matter if the factor is HP or other etiologic agents, the tissue gives similar responses. That is why clinical-endoscopic indications should be taken into consideration, as well as histological indications, and the reports of the endoscopy should be seen. A good clinicopathologic correlation increases the accuracy of the diagnosis. Keywords: Gastritis, gastropathy, classification

Gastritis is an infectious or auto-immunological inflam- images of gastritis based on different etiologies, and mation. Gastropathy can be described as a pathology there may be more than one etiologic agent in a gas- that displays epithelial injury and regeneration, and it is tritis chart. secondary to endogenous or exogenous irritants. Gastritis was categorized as chronic and acute in 1947 In practice, “gastritis” may be accompanied by mucosal for the first time. Then, chronic gastritis was categorized injury, while “gastropathy” may show, even if minimal, into two subgroups: namely, superficial and atrophic. an inflammatory reaction. After Marshall and Warren demonstrated in 1983 that a CLASSIFICATION bacteria called Campylobacter pylori caused gastritis, a There is no universal categorization of gastritis and tendency of an etiology-oriented denotation began. For gastropathy, but they can be categorized according this purpose, a group of gastropathologists prepared a to their duration of development (according to the in- classification in 1990 in Sydney for the first time to clas- flammation type) and acute/chronic etiology. sify and rank gastritis. Within this period, the importance of the findings of gastritis, atrophy, and metaplasia in GASTRITIS Correa’s chart in 1992 was realized, and these findings Gastritis is an inflammatory condition of gastric mu- were included in the first classification. However, due to cosa that displays changes related to etiology and the differences between observers in the rating of especially host response. It was identified in the 1800s as a re- chronic gastritis and atrophy over time, the Sydney clas- sult of autopsies. There may be similar morphological sification was reviewed, and a visual analog scale was

Address for Correspondence: Serra Kayaçetin, Department of Pathology, Ankara Numune Education and Training Hospital, Ankara, Turkey E-mail: [email protected] Received: 10.6.2014 Accepted: 18.6.2014 © Copyright 2014 by The Turkish Society of • Available online at www.turkjgastroenterol.org • DOI: 10.5152/tjg.2014.7906

233 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

prepared by preserving the basic principles. Despite all these Etiology efforts, inconsistencies, especially in the rating of atrophy, drew • Medication, uremia, ischemia, shock, corrosive agent, attention. Thus, the team that made the first Sydney classifica- radiation, sepsis, trauma, acute , severe burns, tion put forward a metaplastic/nonmetaplastic atrophy rating alkaline reflux, surgery in 2002 (1-7). Physiology The morphological changes that are observed in a gastritis • Decrease in mucus secretion chart can be summarized as follows: • Decrease in mucosal blood flow 1. Epithelial degeneration • DNA, PG synthesis

Review 2. Foveolar hyperplasia • Decrease in mucosal barrier 3. Mucosal hyperemia and 4. Neutrophilic infiltration Endoscopy 5. Eosinophilic infiltration • Stress, fundus-corpus; NSAID, antrum 6. Mononuclear inflammatory cell infiltration • Multiple round-shaped severe erosions with a diameter 7. Lymphoid follicles of several millimeters. 8. Atrophy • Mucosal edema, hyperemic 9. Intestinal metaplasia 10. Endocrine cell hyperplasia ACUTE GASTRITIS (Acute erosive/hemorrhagic gastritis- 11. Parietal cell alterations tress-induced gastritis) This is a transient type of gastritis that has an acute beginning, APPROACH TO GASTRIC BIOPSY and it causes gastrointestinal pain and hemorrhage. It can de- Acute velop in a hemorrhagic or nonhemorrhagic, ulcero-erosive or • Edema, congestion, hemorrhage nonerosive manner, and it develops as a result of the stress that • Acute (, eosinophil) the mucosa is exposed to. • Erosion, ulcer 1. Physiological stress Chronic Severe burns, trauma, SSS injury, etc. • Chronic inflammation (lymphocyte, ) • Lymphoid aggregate, follicle 2. Toxic stress, medication, especially NSAII • Atrophy Corrosive substances, alcohol, reflux, etc. • Metaplasia (intestinal, pyloric, pancreatic) Specific (Lymphocytic, Eosinophilic, Granulomatous) 3. Hemodynamic stress Hypovolemia and shock, ischemia, hypotension Reparative, Reactive • Regenerative activity Morphological findings • Foveolar hypertrophy Sharply circumscribed, superficial erosions that are generally • Granulation tissue smaller than 2 mm. These erosions are typically multiple, and they have a tendency to occur in proximal. Ulcerations are SYSTEMATIC ANALYSIS OF BIOPSY smaller than 1 cm, and the base is grayish green, sanguineous, • Localization- corpus, fundus, or antrum and slightly swollen. • Distribution of gastritis (pangastritis) • Gastritis-gastropathy differentiation ACUTE GASTRITIS

CHANGES RELATED TO BIOPSY Microscopy • Edema • Hemorrhage and edema in superficial • Vascular dilatation • Mucosal necrosis, neutrophil infiltration (low) • Hemorrhage in focal lamina propria • Regenerative epithelium, syncytial glandular structure • Flattening in surface epithelia (there is no epithelial de- • Erosive surface epithelium generation or acute inflammation) Differential diagnosis ACUTE GASTRITIS • HP Chronic active gastritis Lymphoplasmacytic inflammation Classification Neutrophilic cryptitis Hemorrhagic, nonhemorrhagic, erosive, nonerosive, diffuse, • Dysplasia and intense (Figure 1). Nuclear stratification

234 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified?

Lamina propria expanded with inflammation Lamina propria with little or no inflammation

Acute Gastritis - Erosion, edema, hemorrhage - Caustic injury, Alcohol - Shock, hypotension Diffuse Focal (s) - latrogenic: Iron, etc... - Radiation Reactive Gastropathy

- Foveolar hyperplasia w/ Review Autoimmune gastritis Focally Enhancing Gastritis Granulomatous Gastritis - "Corkscrew appearance" - NSAID, other drugs - Corpus predominant - Admixed lymphohistiocytic and - Crohn disease - Lymphoplasmacytic infiltrate neutrophilic infiltrate - Bile reflux - Sarcoidosis - (Alcohol) - Parietal cell destruction - IBD, autism, bone marrow - Others: Parasite, Foreign - ECL cell hyperplasia transplant body, Mycobacteria, etc - Unknown (25%) GAVE Lymphocytic gastritis - Rule out other causes even if - Antrum predominant vascular - Increased IELs H. pylori positive ectasia - H. pylori +/- - Intravascular thrombi - History of celiac sprue +/- - Myofibroblastic proliferation - Others: Crohn, HIV, etc... PHG Eosinophilic gastritis - Corpus predominant - Increased intra-epithelial or vascular ectasia lamina propria eosinophils - Edema, congestion - History of allergy, connective - Mural thickening tissue disease, parasites etc. - History of /portal HT Collagenous gastritis GVHD - Subepithelial collagen band - Increased apoptosis - Increased IEL's +/- - Similar changes secondary to - History of sprue, collagenous cytoreductive regimens - Difficult diagnosis within 3 weeks of transplantation

Figure 1. Schematic approach to the diagnosis of non-Helicobacter pylori gastritis Hyperchromasia • Mucus depletion Increased mitosis, regenerated epithelium amphophilic • Mitosis cytoplasm, regular nuclear contour • Chemical gastropathy Mucosal changes Mucosal elongation Variable Smooth muscle hyperplasia Slight congestion, edema Regenerated change Superficial erosion • Biopsy trauma: clinical history, endoscopic findings Massive necrosis Deep ulcers NSAI usage Inflammation degree depends on the severity of the injury Mucosal erosion, petechial telangiectasia, acute hemorrhagic During recovery gastritis, erosion, loss in glands Regenerative changes Foveolar hyperplasia ACUTE EROSIVE GASTRITIS “Acute hemorrhagic gastritis” related to NSAI and alcohol During acute phase Slight or no inflammation • Vascular congestion • Edema and hemorrhage in lamina propria CHRONIC GASTRITIS • Superficial necrosis • HP-related • Polymorphic leukocyte in glands and pits • Autoimmune Gastritis • Ulcer and erosions in surface epithelium • Atrophic Autoimmune Pangastritis • Superficial fibril deposits • Metaplasia

During the recovery phase Classification of gastritis - Etiologic classification • Nuclear hypertrophy, epithelial regeneration • HP-related gastritis • Pit elongation • Other gastritis

235 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

Chronic H. pylori Gastritis - Histopathology Invasive clinical tests  Amount of H. pylori microorganism Rapid urease test (CLO test), culture, molecular tests (PCR)... • Scarce • Colonies HP in tissue • Abundant Hematoxylin-eosin Histochemistry  Severity of the inflammation: Chronic inflammation Immunohistochemistry cell amount Electron microscopy • Mild • Medium Review H. PYLORI - GENERAL DESCRIPTION • Severe Helicobacter Pylori (HP) H. pylori is a curved, gram-negative bacterium that has flagella.  Activity of the inflammation: Amount of 3.5x0.5 μm. • None 1984- Warren-Marshall • Mild • Medium Epidemiology • Severe Fifty percent of the world’s population is infected with H. pylori.

 Intestinal metaplasia This rate is 70% in developing countries, and its prevalence in • Presence of goblet cells our country is 59%-82% • Goblet HC + Paneth cell complete metaplasia • Prevalent/Focal (TURHEP, GÖRHEN, DİSPEN).  Atrophy: Mucosal thickness and decrease in the num- Transmission: Human beings are the only known hosts. It can ber of glands be transmitted via oral-oral, fecal-oral, and environmental fac- • Mild tors. • Medium • Severe PATHOGENESIS CHRONIC GASTRITIS Features that make it easier to survive in the stomach (viru- There are three different forms of chronic gastritis: lence factors): • Antral • Urease enzyme: It produces ammonia and carbon di- • Fundic • Multifocal oxide from endogenous urea, and it tampons the acid around it. It lives in a urease cloud. HP-RELATED GASTRITIS • Motility (flagella): Enables it to swim in viscous mucus. • Proteases: Melt the mucus. Clinical • Adhesins: BabA and LewisB bind the blood-type an- 80% asymptomatic tigens, and this enhances the bonding with cells that 15%-20% morbidity carry these types of antigens. HP virulence? • Toxins: CagA (“cytotoxin association gene A”) Host immune response? Accompanying factors: Smoking, nutrition, etc? More frequent in the HPs of societies with higher rates of stom- Dyspeptic complaints, nausea vomiting, anemia... ach cancer. VacA (“vacuolating cytotoxin gene A”), which is re- sponsible for cell bonds, polarity, and differentiation, is present Endoscopy in every HP strain. It forms vacuoles in the cell. It facilitates the Variable. Affects the antrum in the beginning and advances nutrition of the bacteria. It inhibits apoptosis. to the proximal in time. Corpus-oriented colonization in those who receive antacid treatment. Strains with high virulence are cagA-, vacAs1-, iceA1-positive. HP identification HP in the tissue Noninvasive clinical tests Serum lgG antibodies (ELISA) Histochemistry HP antigen in stool Giemsa, toluidine blue, Alcian yellow, Genta, Thiamine colors, Urea breath test (radioactive urea) Diff-Quick (Figure 2).

236 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified?

Peptic ulcer - an infectious disease!.. Barry Marshall and Robin Warren, who with tenacity and a prepared mind, challenged pre- vailing dogmas… By using technologies generally available…

Helicobacter pylori can hold any part of the gastric mucosa, but it most frequently settles in the antrum and cardia, and it often advances to the fundus with treatment. HP infection starts as acute gastritis, causes neutrophilic infiltration in the cervix por- H&E Diff-Quick tion of the gastric pit, damages the epithelia with neutrophils

Figure 2. H.pylori’s bacillus with HE and Diff-Quick. and HP, and causes desquamation, and as a result, hyperplasia Review develops in order to replace dead cells. Silvering Whartin Starry. The silver subsides and shows it to be bigger. The inflammation process is followed by erosion, ulceration, Difficulty in implementation and artifacts. There are also au- and loss in mucosal barrier. Neutrophilic infiltration in acute tomatized systems available. gastritis is rapidly followed by chronic inflammation. Lympho- Immunohistochemistry (IHK) is expensive for routine. cytes, plasma cells, , eosinophil leukocytes, and HP-negative chronic antral gastritis cells get involved in the process. With the eradication of HP, Low HP density (dense IM, PPI, antibioterapy) neutrophils rapidly disappear while eosinophils disappear Coccoid form? later. Atrophy and lymphoid follicles are more resistant, and if polymorphonuclear leukocytes are still observed despite treat- HP density ment, HP should be examined again. Should the densest surface or the average be assessed? Should the intestinal metaplasia (IM)surface be assessed? Atrophy of the gastric mucosa makes the mucosa thin and thereby causes severe mucosal injury. It is harder for the bacteria to colonize the IM. Instead of aver- age, the density of the gastric mucosa is more appropriate. The As a result of the destruction of glands along with mucosa or densest surface should be assessed. of the glands that get damaged due to prolonged inflamma- tions, atrophy is formed. After the atrophy develops, intestinal Helicobacter pylori, the dominant factor in gastritis etiology, was metaplasia replaces gastric mucosa. actually identified by Kreniz and Luger for the first time on gastric secretions and on the necrotic material on the surface of ulcer- Other changes observed in HP gastritis ated gastric carcinoma. In 1924, Luck and Steh identified evident urease activity in the stomach. In 1939, Doenges showed spiro- Changes in surface epithelium chetes in the stomachs of 43% of 242 autopsies. Then, in 1979, Damage, erosion, and loss of mucus. Fung identified a spirochete in the curves of surface mucus cells in chronic gastritis, and in 1983, Warren and Marshall showed The differences from artifact separation are fibrin, neutrophils. that this bacteria had similar features with campylobacters, and and regenerative changes. the bacteria was named C. PYLORIDIS in 1985. Foveolar hyperplasia Then, plenty of bacteria, which showed similar growth to gram- Increase in length and curving of foveola. negative bacteria, in a medium that was coincidentally planted and left unattended before Easter were found 5 days later. In Causes of foveolar hyperplasia: 1994, bacteriologists included the bacteria in the Helicobacter • Chemical gastropathy group due to its features, such as denitrification, hippurate hy- • hyperplastic polyp drolysis, and sensitivity to cephalotin. • Menetrier’s Disease • Juvenile polyposis Pathogenesis • Ulcer and regeneration adjacent to stoma (3) Apical HC membrane, intercellular junction, weakens the bonds, downwards penetration, intercellular space and LP leukocytes, Regenerative changes , growth factors... “Cellular-humoral response.” The proliferative compartment expands, and foveolar hyper- plasia is observed. It is difficult to distinguish atypical regenera- HP AND 2005 NOBEL MEDICINE PRIZE tive findings from dysplastic lesions. Robin Warren (Pathologist) Pancreatic acinar metaplasia Barry Marshall (Gastroenterologist) Lobules that resemble pancreatic acinus

237 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

In autoimmune gastritis In cardia Along with other metaplasia In intestinal metaplasia focus in antrum Thin granulose and acidophilic in apical Basophilic in basal. Cells with wide cytoplasm enclose the smooth muscle cells.

Pseudopyloric metaplasia

Review In corpus... Difference from real “pyloric” gland No G cells that produce “gastrin” Contains enterochromaffin-like (ECL) cells They excrete pepsinogen I as well as pepsinogen II.

When it is prevalent and if the localization of the biopsy in atro- Figure 3. Glandular microabcess with PNL. phy is not known, it is hard to diagnose. GASTRITIS. In fact, these lymphoid follicles show im- IHK: Gastrin (-) (7) mune response to bacteria. If there are wide and irreg- ular lymphoid follicles or lymphoid follicles that cover Lymphoid follicles most of the mucosa, MALT lymphoma diagnosis should There are no lymphoid follicles in normal stomach mucosa. be considered.

Its presence indicates the presence of HP. Superficial gastritis Band-shaped in superficial mucosa However, it may not disappear months or years after eradica- Lymphocyte, infiltration of plasma cells tion. Follicular gastritis Attention! Wide and irregular follicles should be examined in terms of MALT lymphoma. ACTIVITY: Polymorphonuclear leukocytes (PNLs) Polymorphonuclear leukocytes activity is a good indicator of Endocrine cell hyperplasia “active” or “acute” inflammation. It is a critical indicator for HP (it It is more apparent in . Hyperplasia may be rapidly disappears in the days following the treatment). “linear” or “micronodular.” Dysplasia and endocrine may turn into tumor. Mild: Scarce neutrophils

PPI-related changes Moderate: Apparent neutrophils in glandular epithelium and It is especially apparent in oxyntic mucosa. Vacuolar changes foveola in gland epithelium, acidophil, protrusions like “clout nails” to- wards lumen, hyperplasia in smooth muscle fibers in antrum, Severe: Mucosal erosions and glandular microabscess (Figure 3). vacuolization in parietal cells, and cystic changes in mucosa can be given as examples. There is PNL in the biopsy but I cannot find HP Am I missing? FREQUENTLY USED TERMINOLOGY IN HP GASTIRITIS 1. Cases where HP gastritis is present but cannot be located: • The term ACTIVE GASTRITIS is used to express pres- Prevalent intestinal metaplasia, ulcer/erosion, PPI usage, antibi- ence of chronic inflammation that accompanies enzy- otic usage for another reason, Helicobacter heilmannii gastritis. matically active neutrophils. Chronic inflammatory re- sponse is limited to superficial mucosa in the beginning 2. Gastritis that is not HP-related and that shows focal chronic (superficial gastritis), and then, it becomes deeper, active inflammation, carditis, reactive gastropathies, Crohn and T-lymphocytes increase both in epithelium and in gastritis, or infectious (fungal, viral, etc.) gastritis. lamina propria. INLAMMATION: Mononuclear inflammatory cells • The evidence of lymphoid follicles that contain or do not What is normal is not known. In total, 2-5 lymphocytes, plasma contain germinal centers is identified as FOLLICULAR cell, in “expected” limits in 1 BBA.

238 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified?

Table 1. Updated Sydney Classification Feature Definition Gradind Guidelines Chronic Increased lymphocytes and plasma Mild, moderate, or severe increase in density inflammation cells in the lamina propria Activity Neutrophilic infiltrates of the lamina Less than one third of pits and surface infiltrated = mild; one third to propria, pits, or surface epithelium two thirds = moderate; more than two thirds = severe Atrophy Loss of specialized glands from either Mild, moderate, or severe loss antrum or corpus

Intestinal Intestinal metaplasia of Less than one third of mucosa involved = mild; one third to two thirds = Review metaplasia the epithelium moderate; more than two thirds = severe. Helicobacter H. pylori density Scattered organisms covering less than one third of the surface = pylori mild colonization; large clusters or a continuous layer over two thirds of surface = severe; intermediate numbers = moderate colonization

Plasma cells are normally absent or only a few in number; 3-5 taken in ideal conditions from both the small and the big plasma cells that come together between foveolae or glands curvatures. The biopsy from the antrum should be taken means “mild” chronic inflammation. 2-3 cm far from the pylorus, and the biopsy from the corpus should be taken 8 cm far from the cardia. Lymphocytes <5/100 epithelium cell. The biopsies should be tagged and sent in three separate Lymphocytic gastritis if this increases? bottles (9).

Lymphoid gathering cannot be found in a lamina propria that 2. The pathologist should be aware of the endoscopic find- has not encountered HP. ings, history of the patient, and the part of the stomach that the biopsy was taken from while evaluating the biopsy. Helicobacter pylori may exist for years after its eradication. The Sydney system suggests that chronic inflammation rating be 3. The biopsy sample that will be taken in the full layer from done far from lymphoid follicles (8). the mucosa should be determined in appropriate condi- tions; it should be placed vertically to the mucosa surface, Chronic gastritis according to 1994 Sydney Classification and sufficient mass incision should be taken. 1. ACUTE 2. CHRONIC 4. Appropriate histo/immunohistochemical stains should be NONATROPHIC - apparent gastritis in antrum - H. pylori, diffuse used in order to make a reliable rating of HP. antral gastritis, pangastritis, superficial gastritis, type B 5. H. pylori, chronic inflammation, PNL activity, atrophy, and ATROPHIC - Corpus dominant - Autoimmune, type A metaplasia should be rated and located in each gastritis chart. Multifocal atrophic - H. pylori 6. If there is an intense inflammatory reaction in the biopsy, 3. SPECIAL TYPES - and Gastropathy - Eosinophilic, lymphocyt- ic, infectious, etc. atrophy rating should be avoided, and atrophy should be evaluated in the ambiguous group. However, the term at- SYDNEY 2002 CLASSIFICATION rophy should be used if there is intestinal metaplasia ac- Due to the different points of view among gastrointestinal pa- companying the inflammation. If there is atrophy both with thologists, especially about atrophy, atrophy and intestinal meta- and without metaplasia in the same biopsy, it is a better ap- plasia were reviewed again. Two main phenotypes of chronic proach to evaluate the atrophy with metaplasia, since the gastritis in the new description of atrophy were classified as: metaplasia increases the risk of cancer. • Atrophic • Nonatrophic 7. If the metaplasia is limited to the foveolar epithelium and has not replaced the gastric glands completely, atrophy Updated Sydney Classification (Table 1). should not be referred. In this case, the lesion may be de- scribed with a metaplasia that is limited to the foveolar- Points to take into account while making the Sydney clas- focal or partial metaplasia. sification: 1. Consisting of two from the antrum, two from the corpus, 8. While atrophy without metaplasia is being evaluated, the and one from the incisura angularis, five biopsies should be number of glands in x40 enlargement should be taken as

239 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

the morphological criteria. If the oxyntic tubules get short- HP GASTRITIS ACCORDING TO THEIR PHENOTYPIC AND er, the interglandular distance expands, and additionally, TOPOGRAPHIC FEATURES pseudopyloric metaplasia develops; a distinction from the normal antrum mucosa is not possible. In this case, a di- Non-atrophic gastritis agnosis of atrophy can be made only with the endoscopic Sydney findings. Antral predominant gastritis Non-atrophic pangastritis (or corpus dominant/predominant Rating according to the updated Sydney classification gastritis) In stomach biopsy:

Review - Mononuclear inflammatory cell infiltration Atrophic gastritis - Activity, PNL infiltration Sydney (Autoimmune gastritis/Multifocal atrophic gastritis) - Atrophy Antrum dominant (limited to antrum/antral predominant) - Intestinal metaplasia atrophic gastritis - Rating of HP presence is, according to the visual analog Corpus dominant (limited to corpus/corpus predominant) scale, classified as mild, medium, and severe (10). atrophic gastritis (Autoimmune gastritis is also a type of corpus-limited atrophic Chronic inflammation: In normal gastric mucosa, 2-5 lym- gastritis) phocytes, plasma cells, and macrophages can be accepted as normal; in fact, plasma cells are either nonexistent or very Another classification rare in healthy people. While evaluating chronic inflamma- • Non-atrophic antral predominant gastritis tion, it is necessary to evaluate places far from lymphoid fol- • Non-atrophic corpus predominant gastritis licles. • Non-atrophic pangastritis • Antrum-limited atrophic gastritis Activity: The severity of the intraepithelial PMNs is the most • Multifocal atrophic gastritis sensitive indicator of mucosal injury and presence of H. py- lori, and they are the quickest cells to disappear with treat- Importance ment. Antral predominant non-atrophic gastritis The most common form of HP gastritis. Atrophy: Loss of glandular tissue is considered atrophy. Since Acid secretion could be normal or increased. atrophy is one of the most important steps of gastric carcino- The risk of duodenal ulcer is high. The risk of gastric cancer is low. genesis, the diagnosis and rating of atrophy are very important. Corpus-predominant non-atrophic gastritis Intestinal metaplasia: Intestinal metaplasia in gastric muco- It is generally seen in those who use PPI. sa is diagnosed with the presence of goblet cells, absorptive cells, and colonocytes that contain mucin. Since the lesion Pangastritis (or corpus dominant/predominant non-atro- is often patch-like, it is important to identify the location of phic gastritis) biopsy (11). Acid production decreases. Gastric ulcer is common. The risk of multifocal atrophic gastritis, metaplasia, and cancer Complete: Goblet cells that contain acidic mucin and absorp- is high. tive enterocytes with brush borders. Corpus dominant (limited to corpus/corpus predominant) Incomplete: Irregularly shaped goblet cells and immature- atrophic gastritis intermediary mucus cells The risk of cancer has increased in these cases. It is also called autoimmune gastritis. Type II A or type II: the ones that contain acidic sialomucin TOPOGRAPHIC EVALUATION... WHEN CAN IT BE PER- Type II B or type III: the ones that contain sulfomucin FORMED? The Sydney system/OLGA system suggests that a full set bi- Since pseudopyloric metaplasia often accompanies autoim- opsy be taken in order to make a topographic classification. mune gastritis and endocrine cell hyperplasia, it is important Topographic interpretation can only be made if there is a full to diagnose. This kind of metaplasia should also be accepted set, appropriate tagging, and endoscopic report. as evidence of atrophy. How should we report if the biopsy is not full set? H. pylori: H. pylori activity in the stomach should be evaluated in In fact, most HP gastritis and non-HP gastritis/gastropathies places where there is no intestinal metaplasia. could be evaluated with a few samples.

240 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified?

However (attention) Systematic sampling and tagging is necessary for Atrophy rating-staging

Metaplastic Atrophic Gastritis (MAG)-Autoimmune distinction Pseudopyloric metaplasia evaluation (if there is no gastrin IHK) Otherwise, interpretation regarding topographic dispersion should be avoided.

Even in benign lesion diagnosis, biopsies should be taken Review from the right place, with the sufficient amount. For instance, since the microorganisms may be dispersed in a patch man- ner in Helicobacter pylori gastritis, Helicobacter pylori may be negative if multiple samples are not taken from different localizations. Similarly, if the biopsy is taken from the middle and surface of an ulcerous lesion, a carcinoma that causes Figure 4. Nuclear hiperkromazi, nucleus/stoplazma percent increase seen ulceration underneath or a lymphoma infiltration cannot be in the regenerative atypia. detected, since only an inflammatory and necrosis non-neoplastic and how the follow-up and the treatment of will be seen. the patient will be directed afterwards. The size of the biopsy is also important. In very small mucosa Diseases that are related to H. pylori biopsies, even the diagnosis of benign lesions is difficult. The presence, activity, and atrophy of a gastritis or intestinal meta- • Chronic gastritis - 90% plasia cannot be evaluated in small biopsies that contain only • Peptic ulcer - 95%-100% foveolar epithelium and too little lamina propria. In small bi- • Gastric adenocarcinoma - 70% opsies taken from malignant lesions, a few groups of malig- • Gastric lymphoma (MALT lymphoma) nant cells or a few tumoral glands or a few malignant cells, a • Reflux ? large part of which is in necrotic fragments, can be observed. • Non-ulcer dyspepsia Besides the high probability of a carcinoma or a malignant tu- moral process, it may be difficult to make a final diagnosis. Col- HP AND GASTRIC CANCER laboration of clinicians is very significant in this kind of case. Helicobacter pylori prevalence is 80%. Why do some people have cancer while others do not? Technically, another important problem is the mechanical artifact that is made by the biopsy forceps. When the benign Why is there an apparent atrophic background in some can- nature glands get squeezed and lose their normal shape as a cers while there is none in others? result of contusion artifacts, they may face carcinoma. Since the cell nuclei in the artifacts, which are at the margin of the Inflammation pattern- risk of cancer... IL-1 beta gene polymor- biopsy, are stained larger and darker than normal, they may be phism? thought to be dysplasia or carcinoma. The mononuclear cells that are in the normal limits in the mucosa may appear to be Every step of the cascade... More apparent in societies where in great numbers as a result of contusion artifacts and thus be the risk of gastric cancer is high! thought to be inflammation or lymphoma infiltration. HP is a strong risk factor in distal gastric cancers. But, its rela- Another condition for a correct diagnosis is an examination tionship with gastric cardia? (lowers the risk?) in incisions that are prepared in optimal conditions that dis- play full-layer mucosa and that are stained with well-oriented No genetic-molecular difference in HP-related/non-HP tumors! hematoxylin-eosin (H.E). In addition to the fact that histo- chemical, immunohistochemical, and molecular methods are WHO-IARC... HP type 1 carcinogen! frequently used and are helpful in differential diagnosis, the golden standard is still the examination of incisions that are Chronic inflammation- increased cellular “turn-over” - increased stained with H.E. mitotic failure - increased rate of mutation (12).

Despite some other problems that are faced in the evaluation Correa pathway / Correa cascade of benign lesions in endoscopic biopsies, the main problem is Chronic gastritis the differential diagnosis of whether the lesion is neoplastic or Atrophic gastritis

241 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

Intestinal metaplasia as presence of abnormal mitosis, back-to-back gland pattern, Dysplasia and budding, and papillary formation (13).

Gastric cancer In endoscopic biopsies, after diagnosing dysplasia, the second In lesions that are formed by Helicobacter pylori or non-ste- crucial point is the distinction of high-and low-grade dysplasia, roidal anti-inflammatory drugs (gastritis, ulcer/adjacent to ero- and especially in an intramucosal carcinoma diagnosis, various sion) and especially in the intestinal metaplasia zone, it could histopathological approaches among pathologists is a much- be difficult to differentiate regenerative changes from low- debated issue. Especially, this difference is presented by Jap- grade dysplasia. anese and Western pathologists in great numbers of studies

Review (14). Although an apparent invasion is not seen in most of the Besides the fact that ulcer/erosion adjacency or intense active high-grade dysplastic lesions, Japanese pathologists evaluate inflammation is mostly considered to be in favor of regenera- it as intramucosal carcinoma (15). While Japanese pathologists tion, it should not be forgotten that active inflammation can evaluate only in accordance with the degree of cytologic and also be observed in low-grade dysplasia. The regenerative structural atypia, the incidence of lamina propria invasion is an changes being limited to the glands’ proliferative zone and not indispensable criterion in the West (16-18). In order to prevent advancing to the surface epithelium and absence of structural this difference and to make the whole world use the same ter- deformation are useful for diagnosis. minology, the Padua and then Wien classifications were made, In the Padua classification that was made in 2000, dysplasia and based on the Wien classification, the WHO-2000 classifica- was named non-invasive neoplasia (NIN) and “indefinite” group tion was made in 2000 (19,20). There has not been any change lesions, in which regenerative atypia and dysplasia (NIN) could in the WHO-2010 classification. not be differentiated, and was classified into two subgroups in order to make a better identification. Diagnosis according to Western pathologists: - High-Grade Dysplasia 1. Foveolar hyperproliferation (seen with erosion or ulcer, no intestinal metaplasia) Diagnosis according to Japanese pathologists: - Intramucosal Carcinoma 2. Hyperproliferative intestinal metaplasia (back-to-back gland pattern, consists of medium/high number of intestinal In the grading of dysplasia, the triplet system (low-, medium-, glands with mitotic character). The main problem in the di- high-grade dysplasia) had been used for many years. However, agnosis is the hyperproliferative intestinal metaplasia type. the dysplasia classification formed by Riddell et al. in 1983 in inflammatory bowel diseases was found to be very practical Atypia is the most important histopathologic finding that de- and was applied to the stomach as well. It started to be used in termines the lesion’s nature. In general, it shows that the cell’s many centers in the form of a doublet grading system, which proliferative activities, such as hyperbasophilia, nuclear and was dysplasia-negative, indefinite group for dysplasia and nucleolar growth, increased mitotic activity, and decreased cell low or high grade for dysplasia positive. Cases diagnosed as maturation, have increased. In addition to the fact that it can be “indefinite dysplasia” in which dysplasia and regenerative/reac- seen in benign lesions, it is a feature of real neoplastic epithe- tive atypical changes can not be differentiated are immediately lium, such as dysplasia or cancer. recommended to have a certain diagnosis by a new biopsy or biopsies of pursuance after the treatment. The answer to the Atypia is in 3 main types: question about whether it is real dysplasia or regenerative/re- active hyperplasia is one of the most important problems of 1. Reactive atypia: It develops as a response to tissue injuries, this routine. The increase of the expression and its discontinuity such as acute inflammation or radiation. in the surface ımmunohistochemical that shows the activity of proliferative Ki67, PCNA, the existence of the expression of P53, 2. Regenerative atypia: It develops as a regenerative response intestinal differentiation (cdx2), immortalization (hTERT), MU- to benign ulcer or erosion (Figure 4). C5AC, MUC 6 expression ptosis, recently defined α-Methylayl- CoA-Racemase (AMACR) expression are used as assistant 3. Precancerous atypia (dysplasia/intraepithelial neoplasia): It methods in dysplasia diagnosis (21). However, in most of the develops as a neoplastic process without relation to reac- studies, it is seen that molecular markers are limited in distin- tive or regenerative causes, and it is a change of epithelium guishing the atypical hyperplastic lesions from low-grade dys- that has a risk of developing cancer. plasia (NİN). The second important point in endoscopic biop- sies after the diagnosis of dysplasia is made is correct grading, In addition to the aforementioned cytologic features of atypia, because the biological meanings and treatment approaches of there are also structural deformations, such as nuclear polar- low- and high-grade dysplasia are very different to each other. ity loss in epithelium in real dysplasia, multiple ranks, as well As can be seen, there are still no objective measures put for-

242 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? ward in dysplasia diagnosis and grading. The support of im- intestinal metaplasia of the glandular area, it should be evalu- munohistochemical and other molecular methods is limited. ated as atrophy. Incisions stained with gold standard H.E. and another patholo- gist’s (experienced in gastrointestinal systems) confirmation of CHRONIC GASTRITIS STAGING (OLGA staging) the diagnosis are recommended. Operative Link for Gastritis Assessment (OLGA) Gastroenterologists and pathologists ATROPHY It is a system “staging” morphologic changes (atrophy) accord- In its new description, atrophy is described as “loss of the ap- ing to increased risk of cancer from 0 to IV. propriate glands (native glands in a specific surface);” so, meta-

plasia is added to the description of atrophy. Atrophy: None/metaplastic/nonmetaplastic atrophy/indefi- Review nite atrophy Two kinds of atrophic lesions are defined: ATROPHY 1. With the replacement of native glands by epithelia-show- Mild: 1%-30% ing metaplasia-atrophy related to metaplasia Medium: 31%-60% Severe: 61%-70% (the cystic dilatation of the gland is together 2. The decrease of the density of native glands and character- with the epithelial atypia and intestinal metaplasia); 16 times ized by the increase in interglandular extracellular matrix- increased risk of malignancy. nonmetaplastic atrophy The risk of malignancy increases by 11% when atrophy and in- testinal metaplasia are together. It is possible to observe both metaplastic and nonmetaplastic atrophy in one patient; in such cases, as metaplasia increases HP GASTRITIS EVALUATION the risk of cancer, priority should be given to the diagnosis of Helicobacter pylori gastritis is a perpetual and “chronic” gas- atrophy related to metaplasia. tritis.

“the loss of the glandular tissue and thinning of mucosa,” in the Some of the changes are not characteristics of HP gastritis. original Sydney system. Grading Staging • Functional atrophy (Atrophy Club). Sydney Classification OLGA Staging system (<10 years) • It is normal to have 4-5 lines of glands on the muscularis (1996-Houston) Gastritis- atrophy-cancer relation mucosa Intensity of observed Whom to follow? • Antrum, corpus changes • It is difficult to determine the grade of atrophy in the Follow-up? It grades atrophy antrum rather than corpus. Normally, in the antrum, glands are in loose stroma and gastric pits are longer, Important points to pay attention to in atrophy associated and there is dense inflammatory cell infiltration in HP. with metaplasia Glands are denser in the corpus. • If the metaplastic change is limited in the foveolar part • Parietal cells and core cells lie on the neck of the gland. of the gastric gland, atrophy should not be mentioned. The reticulin dips among the pits. “the loss of appropri- The term atrophy should be used when all segments of ate glands”(22). the original glandular unit go to metaplasia. • Goblet cells, scattered and few in number, are a fre- Negative for atrophy: There is no indication of the loss of the quent indication, especially in H. pylori-related gastritis. gland when a sufficient number of samples is taken. If limited These lesions should be depicted as limited in foveola, intestinal metaplasia in the minimal focus or in foveola does partial, etc. not cause loss of gland, it should be evaluated as negative for • Metaplastic atrophy should be classified as mild, medi- atrophy. um, and severe. There is sporadic intestinal metaplasia of a gland in atrophy with mild metaplasia, and there is Indefinite for atrophy: If there is apparent inflammation, lym- prevalent metaplasia in the severe form. phoid aggregates, and follicles in the lamina propria, antral glands and oxyntic glands secreting mucin could be masked METAPLASIA by inflammation. While defining the phenomenon, it is nec- • Pyloric essary to use the description of indefinite for atrophy and to • Intestinal ask for a new biopsy again in such a case. Generally, atrophy • Pancreatic indications retreat after several months of successful eradica- • Cilia cell tion treatment. However, if the inflammation is with all of the Intestinal and pyloric metaplasia is frequent in HP.

243 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

Native glands can change positions with mucus cervix cells or CHRONIC REACTIVE (CHEMICAL) GASTROPATHY mucus-secreting glands in oxyntic compartment- pseudopylo- It is more frequent in antrum ric metaplasia. This view is frequently associated with advanced NSAI drug use autoimmune gastritis and endocrine cell hyperplasia. It should Gall reflux (stomach surgery) be evaluated as atrophy related with metaplasia in such cases. Mucosal edema, congestion Foveoler hyperplasia like “corkscrew” It could be difficult to distinguish native glands replacing the Fibromuscular hyperplasia in LP nonatrophic antral gastritis and metaplasia with pseudopyloric (increase of smooth muscle tendons, their stretching towards oxyntic mucosa in the incisura angularis; in these areas, only the surface)

Review intestinal metaplasia should be used to define gastric atrophy. Regenerative changes Chronic inflammation is not as dense as HP INTESTINAL METAPLASIA Erosion might develop According to histological features similar to colon and intestine Infiltration of eosinophils Brush border, paneth cell, goblet cell… Mucin ingredient is evaluated as complete/incomplete Differential diagnosis… To determine the mucin ingredient Regenerative mucosa shifts around the ulcer (presence of ulcer) PAS Foveolar hyperplasia related to HP Alcian blue pH 2.5 (presence of medium-severe inflammation on the ground) Alcian blue pH 0.5 Hyperplastic polyp (presence of endoscopic polyp) The combinations of these with high iron diamine are used. Gastric Antral Vascular Ectasia (GAVE) It is related with HP. As the required features are in the epithelium for , HP LYMPHOCYTIC GASTRITIS can not colonize in intestinal metaplasia areas. Chronic gastritis continuing with the increase of intraepithelial T lymphocytes (İELs) Foveolar epithelium of gastric containing neutral mucin, pH 2.5, is stained pink with PAS-Alcian blue; acidic glycoproteins in Etiology… most frequently, it accompanies gluten-sensitive intestinal metaplasia are stained with blue-purple. (40%) and HP gastritis (20%)

As type III metaplasia has a more apparent relation with cancer, Histomorphological indications… sulfomucin HID/AB with its special dye is stained brown, while si- alomucin is stained blue. However, the requirement of the color- İEL >25 lymphocytes/100 epithelial cells ing should be debated, as it is difficult to distinguish metaplasia Both in the surface and in the foveolar epithelium involving sulfomucin, and it requires expensive methods. In HP gastritis, it is 1/10 Most of it is CD3 (+) T lymphocytes HELICOBACTER HEILMANNII (HH) GASTRITIS CD8 coexpressed Helicobacter Heilmannii, gram-negative bacillus Involvement is in the form of either patch or diffuse It is 5-9 μm longer than HP, and it has a spiral shape Involvement of corpus is more frequent It generally causes a milder focal gastritis in the form of a patch More frequent in children Differential diagnosis...HP gastritis. Lymphoma Infection: From livestock or pets Treatment... Towards the accompanying pathology Responds to steroids as well. It may regress spontaneously. Alkaline Reflux Gastritis Foveolar hyperplasia GRANULOMATOUS GASTRITIS Similar to hyperplastic polyp It is a descriptive diagnosis. Villiform transformation Infections Irregular glands containing gall crystals Tuberculosis, histoplasma, Taenia, strongyloides, H. pylori Acute Suppurative (Phlegmonous) gastritis… Systemic diseases Generally old, alcoholic, addicted people Crohn disease, Sarcoidosis, CVID, An acute chart that could be fatal Wegener granulomatous… Agent factors are bacteria, such as streptococcus, staphylococ- Foreign bodies: Suture material, cus, E. coli and proteus. (infectious gastritis) barium, mucus, “food granuloma” It is frequently seen in laparotomy biopsies or autopsies Idiopathic; in 25% of the cases, there is no etiologic agent (it is Dense submucosal and mural intense PNL infiltration, mucosal also called isolated idiopathic granulmatous gastritis) fall, and necrosis are seen frequently Clinic…It depends on the related illness.

244 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified?

Histology Fungis Caseification necrosis - tuberculosis Candida… Large compact surrounded by lymphocytes in Colonized in 20% of benign gastric ulcers … normal mucosa - sarcoidosis Most of them recover with antacid treatment without the ne- Eosinophilic infiltration - parasitic disease cessity of additional antifungal treatment. Ulcer edge - “food granuloma” Not having plasma cells - CVID Aspergillus (Mucor)… Localized in antrum, HP-negative focal chronic active gas- The invasive forms are almost always fatal. It is an “emergency/ tritis - Crohn H. panic” diagnosis. Review GASTRIC CROHN DISEASE PORTAL HYPERTENSIVE GASTROPATHY The “gastric-dominant/gastric beginning” forms of the illness Related to in cirrhotic or noncirrhotic patients. are <4% of all Crohn cases Endoscopy: appearance like “snake skin” caused by mucosal Endoscopic changes or inflammation in 15% of people who edema and erythema have Crohn disease; microscopic mucosal changes or inflam- mation in 75% Antrum is typically preserved.

The indications are the same with intestinal Crohn disease. Histopathologic indications … Dilate capils and vens in mucosa and submucosa. SPECIFIC GASTRITIS TYPES Differential diagnosis … Collagenous gastritis: It is characterized with the existence of subepithelial thick acellular collagen bands. GAVE (fibrin thrombus) fibrovascular proliferation is seen. AUTOIMMUNE GASTRITIS Radiation gastritis: It is scarcely seen; necrosis, edema, and mononuclear inflammatory cell infiltration are seen in fundic Histomorphologic indications… glands. It is a reversible event. Changes are in oxyntic mucosa. Antrum is preserved. 1. Chronic gastritis (lymphoplasmocytic infiltration that is Infectious gastritis: It is a gastritis emerging from factors, denser in depths of mucosa). such as mycobacterium avium intracellular, treponema palli- 2. Atrophy (it is lost in oxyntic mucosa; parietal and chief cells) dum. CMV observed in people who have immune deficiency. 3. Metaplasia (intestinal metaplasia, pseudopyloric metapla- sia, pancreatic acinar metaplasia) Carditis: The inflammation of the cardia is generally with gas- 4. Neuroendocrine cell hyperplasia (linear or nodular) trointestinal reflux; if there is no H. pylori, generally acute in- flammation is not seen. Indications change according to the stage of the illness. In Early Stage: dense inflammation, metaplasia in form of patch COLLAGENOUS GASTRITIS Etiology… In Fluoride Stage: diffuse inflammation, apparent atrophy, Unknown metaplasia, ECL-like neuroendocrine cell hyperplasia Co-occurrence with other collagenous intestinal and autoim- mune diseases In Advanced Stage: slight inflammation, apparent atrophy and Both in pediatric and adult groups metaplasia±foveoler hyperplasia, microcystic changes. Intestinal and autoimmune defects do not accompany in children. Histopathology… Mucosa may look like (complete intestinal Subepithelial collagen thickening (> 10 μm) (on average 30-40 μm). metaplasia). Surface epithelial damage and accompanying inflames Involvement could be in patch form or diffuse (23) Autoimmune Gastritis Chronic or active inflammation, intraepithelial lymphocytosis, Synonym: Type A gastritis, fundic gastritis, diffuse corporal intestinal metaplasia±HP. atrophic gastritis, autoimmune chronic gastritis

INFECTIOUS GASTRITIS Epidemiology: Northern Europe - Scandinavia, in females CMV gastritis… It is seen in immunosuppressive people. Etiology: Immune attack: In acid-secreting mucosa, a progres- It is appropriate to take biopsy in ulcer lesions from the basis sive destruction affecting mainly parietal cells and chief cells. of the ulcer. H. pylori: <20%

245 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified? Turk J Gastroenterol 2014; 25: 233-47

Laboratory: Anti-parietal HC, antibodies (+) Nausea, vomiting, , obstructive symptoms Anti-İF antibodies (+) Histomorphologic indications… B12: Low (pernicious anemia) Mucosa is normal, erythematous, ulcerous, or hypertrophic.

Gastrin: Very high Eosinophilic microabscess might be seen.

Histology: KG, atrophy in oxyntic mucosa, metaplasia, NEH, Differential diagnosis… G-HC hyperplasia in antrum. Parasitic infections, drug reactions, inflammatory bowel disease Review Multifocal atrophic gastritis Treatment and prognosis… Synonym: Peripheral chronic atrophic gastritis, peripheral It gives a dramatic response to steroid. metaplastic atrophic gastritis, atrophic gastritis type AB, atro- phic pangastritis GENERAL APPROACH TO GASTRITIS-SUMMARY Most of the gastritis types can be recognized by H & E- Epidemiology: the whole world, female = male stained tests. While evaluating biopsy, the answers to the questions below will ease the specific diagnosis towards the Etiology: HP (mis-hygiene?) (frequent in Japan, rare in Africa) etiology. HP: 90%-100% 1. Are there any indications of chronic gastritis? (lymphocyte Laboratory: Anti-parietal HC, antibodies: negative and plasma cell infiltration in LP are chronic gastritis indica- Anti-İF antibodies: normal tors, Sydney Classification) B12: normal Gastrin: normal or low 2. Is there PNL in the mucosa? (it is an indicator of active gastritis)

Histology: There is no NEH in the corpus. 3. Is there HP? (when needed, special stains could be used)

AUTOIMMUNE GASTRITIS 4. Is there glandular atrophy or intestinal metaplasia? It constitutes 10% of chronic gastritis. Hypochloride, achlor- hydria progress with high serum gastrin. Generally, there is 5. Is there any specific feature in the division of lesions (topog- no symptom; 90% antiparietal cell immune bodies and 60% raphy)? Is it antral predominant? Is corpus-fundus predomi- anti-intrinsic immune bodies are positive. Glandular atrophy, nant? Is it holding the whole stomach? especially corpus and fundus mucosa, is dominant. Diffuse and deep lymphoplasmocytic infiltration is seen in the lamina pro- 6. Are there any special indications? (granuloma, foveolar hy- pria. There is linear and nodular neuroendocrine cell metapla- perplasia, viral inclusion?) sia and parietal cell pseudohypertrophy. Oxyntic glands disap- pear and give their place to glands (pseudopyloric metaplasia) 7. Is an additional examination needed? What are the conse- producing neutral mucin (periodic acid-Schiff-positive). quences?

EOSINOPHILIC GASTRITIS CONCLUSION Diagnosis Stomach endoscopic biopsies are made to determine the di- 1. Dense eosinophilic infiltration in stomach agnosis of the illness, its stage, and follow-up after the treat- 2. Presence of Gl symptoms ment. It is very significant to collaborate with the clinician 3. Excluding the pathologies that may cause eosinophils while evaluating endoscopic biopsies. Besides the clinical Minimal eosinophil density? and laboratory information of the patient, the endoscopic At least 20 eosinophils/BBA appearance of the lesion should be known. The clinician and Involvement may be in the form of patch, or it may be prevalent. pathologist should use the same language and the same ter- minology. Although new classifications have been made to Etiopathogenesis… prevent the confusion of terminology in neoplastic processes Genetic factors, food allergens, interleukins (especially IL-5, IL-3, recently, most of the centers around the world report non- and GM-CSF) and chemokines (CCL-5/RANTES, CCL-11/eotaxin) invasive neoplasies without giving any certain diagnosis, by just commenting on it. Clinicians should understand what Clinical… the pathologist wants to say, and pathologists should know Atrophy history, peripheral eosinophils, increasing of serum IgE the approach of the clinician (repetition of the biopsy, endo- 20% in pediatric age group scopic resection, surgery).

246 Turk J Gastroenterol 2014; 25: 233-47 Kayaçetin and Güreşçi. What is gastritis? What is gastropathy? How is it classified?

There is HP in most of the stomach pathologies as the etiologic 10. Ozturk S, Serinsoz E, Kuzu I, et al. The Sydney System in the assess- agent. No matter the factor is HP or other etiologic agent, the ment of gastritis: Inter-observer agreement. Turk J Gastroenterol tissue gives similar responses. This is why clinical-endoscopic 2001; 12: 36-9. indications should be taken into consideration as well as his- 11. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grad- tological indications, and the reports of the endoscopy should ing of gastritis. The updated Sydney System. International Work- be seen. A good clinicopathologic correlation increases the ac- shop on the Histopathology of Gastritis, Houston 1994. Am J Surg curacy of the diagnosis. Pathol 1996; 20: 1161-81. [CrossRef] 12. Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of Ethics Committee Approval: N/A. the digestive system. World Health Organization classification of tumours. Lyon: IARC Press; 2000. Informed Consent: N/A. Review 13. Stolte M. Diagnosis of gastric carcinoma: Japanese fairy tales or Peer-review: Externally peer-reviewed. Western deficiency? Virchows Arch 1999; 434: 279-280. [CrossRef] Author contributions: Concept - S.K., Design - S.K., Supervision - S.K., 14. Schlemper RJ, Kato Y, Stolte M. Review of histological classifica- S.G.; Analysis&/or Interpretation - S.K., S.G.; Literature Search - S.K.; Writ- tions of the gastrointestinal epithelial neoplasia: Differences in ing - S.K.; Critical Reviews - S.K. diagnosis of early carcinomas between Japanese and Western Conflict of Interest:No conflict of interest was declared by the authors. pathologists. J Gastroenterol 2001; 36: 445-56. [CrossRef] Financial Disclosure: The authors declared that this study has re- 15. Schlemper RJ, Hirata I, Dixon MF. The macroscopic classification of ceived no financial support. early neoplasia of the digestive tract. Endoscopy 2002; 34: 163-8. [CrossRef] REFERENCES 16. Cornberg M, Enss ML, Makkink MK, et al. Variation of human mucin 1. Massimo Rugge MD, Robert M, Genta MD. Staging and grading of gene expression in gastric cancer cell lines and gastric mucous cell chronic gastritis. Hum Pathol 2005; 36: 228- 33. [CrossRef] primary cultures. Eur J Cell Biol 1999; 78: 832-41. [CrossRef] 2. Aydin O, Egilmez R, Karabacak T, Kanik A. Interobserver variation 17. Price AB. Classification of gastritis-yesterday, today and tomorrow. in histopathological assessment of Helicobacter pylori gastritis. Verh Dtsch Ges Pathol 1999; 83: 52-5. World J Gastroenterol 2003; 9: 2232-5. 18. Schlemper RJ, Itabashi M, Kato Y, et al. Differences in the diagnos- 3. Price AB. The Sydney System: Histological division. J Gastroen- tic criteria used by Japanese and western pathologists to diag- terol Hepatol 1991; 6: 209-22. [CrossRef] nose colorectal carcinoma. Cancer 1998; 82: 60-9. [CrossRef] 4. Price AB, Misiewicz JJ. Sydney classification for gastritis. Lancet 19. Schempler RJ, Riddell RH, Kato Y, et al. The Vienna classification of 1991; 337: 174. [CrossRef] gastrointestinal epitelial neoplasia. Gut 2000; 47: 251- 5. [CrossRef] 5. Demir M, Neşe N, Saruc M, et al. Features of incisura angularis bi- 20. Stolte M. The new Vienna classification of epitelial neoplasia of opsies in dyspeptic cases. Turk J Gastroenterol 2001; 12: 211-3. the : advantages and disadvantages. Vir- 6. El-Zimaity H, Ramchatesingh J, Saeed MA, et al. Gastric intestinal meta- chows Arch 2003; 442: 99-106. plasia: Subtypes and natural history. J Clin Pathol 2001; 54: 679-83. 21. Piazuelo MB, Haque S, Delgado A, Du JX, Rodriguez F, Correa P. [CrossRef] Phenotypic differences between esophageal and gastric intesti- 7. Rugge M, Correa P, Dixon MF, et al. Gastric mucosal atrophy: in- terobserver consistency using new criteria for classification and nal metaplasia. Mod Pathol 2004; 17: 62-74. [CrossRef] grading. Aliment Pharmacol Ther 2002; 16: 1249-59. [CrossRef] 22. Rugge M, Genta RM, OLGA Group. Staging gastritis: An interna- 8. Alderuccio F, Toh BH. Immunopathology of autoimmune gastritis: tional proposal. Gastroenterology 2005; 129: 1807-8. [CrossRef] lessons from mouse models. Histol Histopathol 2000; 15: 869-79. 23. Stolte M, Meining A. The updated Sydney system: classification 9. Nomura A. Searching for the causes of gastric cancer. Hawaii Med and grading of gastritis as the basis of diagnosis and treatment. J 2002; 61: 33-4. Can J Gastroenterol 2001; 15: 591-8.

247