GASTROENTEROLOGY
1992;102:355-359
Grading and Classification of Chronic Gastritis: One American Response to the Sydney System PELAYO Department Department
CORREA
and JOHN H. YARDLEY
of Pathology, Louisiana State University Medical Center, New Orleans, Louisiana; and of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
A
new classification of chronic gastritis coined the Sydney system has been proposed as a “flexible matrix of rules.“‘* The system claims that “the recognition that Helicobacter pylori is the major cause of chronic inflammation of the human gastric mucosa has in part solved this problem”. As is often the case, the enthusiasm over new medical findings may have led to overinterpretation. Chronic gastritis is a multifactorial disease, and its biological characteristics are stil1 poorly understood. H. pylori is undoubtedly an important etiologic factor but not the only one. The purpose of this article is to give the reader our reasons for believing that the Sydney system has major flaws in regard to both its underlying premises about the nature of chronic gastritis and in its approach to classifying these disorders. Furthermore, we believe that those flaws are so serious that they could have a detrimental effect on progress in understanding chronic gastritis if the Sydney system becomes widely accepted. We have necessarily given our contrasting views about gastritis by reference to terminology and approaches previously reported by one of US,~but our primary purpose is not mere advocacy of one particular system. We fee1 strongly that understanding of chronic gastritis, spurred by recent exciting discoveries, continues to evolve and that its evolution should not be impeded by accepting questionable inferences on etiopathogenesis and by premature attempts to establish a universal system of classification. The Sydney System The Sydney system recommends that the diagnosis of gastritis be made by integration of information on its etiology, histopathology, and endoscopy, as shown in Figure 1. It further recommends that the same grading categories (mild, moderate, and severe) be used for histological and endoscopic variables without considering the poor record of interobserver reproducibility of such exercises. The system assumes that al1 forms of chronic gastritis are one nosologic entity, with the exception of forms with a specific etiology. It further assumes that it is a
progressive disease in which al1 types of advanced lesions, regardless of topography or morphology, are sequentia1 events of common precursors and suggests H. pylori (apparently in isolation from other etiologic factors) as the cause of the condition. The Sydney system proposes that “the microscopic details of the gastritis are documented in the main body of the pathologist’s report by a series of SUFFIX phrases, the major variables being graded using a common uniform scale. In the conclusion, the topographic summary phrase is PREFIXED, if sufficient data are available, by the etiology or by the most likely etiologic association.“’ This amounts to a grading scheme for each main area of the mucosa (antrum and corpus) prefixed by an etiologic opinion. A system of grading histological parameters by topography could indeed be the basis for a classification but is not in itself a classification, defined as a categorization of nosologic entities. The Sydney system recommends “a minimum of two biopsies from the anterior and posterior walls of the antrum and corpus” (ignoring the incisura). It thus ignores that in the multifocal atrophic gastritis (MAG) nosologic complex, the earliest and most advanced lesions are usually found in and around the incisura. The system creates new problems for the pathologists by unwisely stating that “attempts to orient biopsies are unnecessary.” The endoscopic component proposes that edema, erythema, friability, exudate, erosions, hyperrugosity, fold atrophy, visibility of vascular pattern, bleeding spots, and granularity be graded and used to classify the gastritis. The present critique addresses mostly the etiology and pathological aspects of the Sydney system, but we cannot avoid expressing disagreement with implying a correlation between pathological and endoscopic findings in chronic gastritis. The limited potential of endoscopy in classifying gastritis has been noted by many authors. The Sydney system is accompanied by a summary 0
1992 by the American Gastroenterological 0016-5085/92/$3.00
Association
356
GASTROENTEROLOGY Vol. 102. No. 1
CORREA AND YARDLEY
ETIOLOGY (prefix)
TOPOGRAPHY (core)
MORPHOLOGY (suffix) TOPOGRAPHY Pangastritis
ACUTE GASTRITIS CHRONIC GASTRITIS SPECIAL FORMS
-
Gastritis of antrum
Inflammation
Gastritis of corpus
- Activity
ETIOLOGY
+ Pangastritis
GRADED VARIABLES
- Atrophy
Descriptive terms
Intestinal metaplasia
PATHOGENIC ASSOCIATIONS
Edema Erythema Friability Exudate Flat erosion Raised erosion Nodularity
Helicobacter pylori
Gastritis of antrum
Gastritis of corpus
NONGRADED VARIABLES
I
I
Rugal hyperplasia Rugal atrophy Visibility of vascular pattern Intramural bleeding spots
Categories of endoscopic gastritis
I
P
Specific
Figure 1. The Sydney system. Severity grading: none, mild, moderate, and severe.
review of some of the classifications available and some comments on the epidemiology and natura1 history of gastritis. The latter is mostly based in the Finnish system of grading (not classifying) gastritis.4 To provide a perspective of the developments that have led to the present state of confusion, a different view of such developments is hereby offered, followed by comments on how they conflict with the Sydney system. Scope of Classification
Problems
The present dilemma concerns only the most common types of chronic gastritis, sometimes called nonspecific. There is no important controversy about the specific forms of gastritis. These refer to well-defined entities such as sarcoidosis, tuberculosis, and eosinophilic gastritis. Recently, two new specific forms of gastritis have been recognized: lymphocytic gastritis, which may be related to intestinal malabsorption syndromes,5*6 and reflux gastritis, originally described in postgastrectomy specimens and recently linked to nonsteroidal antiinflammatory drugs and other “chemical” injuries.“’
Two Types
ofAtrophic
Gastritis
Al1 major publications recognize the existence of two types of atrophic gastritis characterized by gland loss and intestinal metaplasia. First recognized was the type associated with the pernicieus anemia syndrome, limited to the oxyntic mucosa, and not usually associated with gastric ulcer but linked to a higher risk of gastric carcinoma originating in the previously metaplastic corpus mucosa. It has received a variety of names: gastric atrophy,g body atrophy,” type A,” diffuse atrophic gastritis,” and diffuse corpora1 atrophic gastritis (DCG).3 It is also referred to as autoimmune gastritis.13,14 Table 1
Table 1. Morphological Not atrophic Superficial (SG) Diffuse antral [DAG) Atrophic Diffuse corpora1 (DCG) Multifocal (MAG)
Classification
of Chronic Gastritis
GRADING AND CLASSIFICATION
January 1992
of Independent
Foei ofïntestinal
357
The problem arises when such a grading system is adopted as a classification, which the Sydney system does, thereby melding two diseases into one. Siurala et a1.4present their contribution as a system for grading, not for classifying atrophic gastritis. They refer to DCG as pernicieus anemia type and to MAG as the genera1 population type. However, they present a controversial speculation implying that the two diseases are one and the same when they state that “it is possible that the only essential differente between the pernicieus anemia type and the gastritis prevailing in the genera1 population is the dynamics, i.e., in the speed of progression of the body gastritis. . . .” Had they had experience with populations free of pernicieus anemia, they would probably have come to a different conclusion. Glass and Pitchumoni” recognized the coincidence of the two types of atrophic gastritis. They proposed the name type AB- (with negative parietal cel1 antibodies) corresponding to MAG. The type they cal1 AB+ (with parietal cel1 antibodies) probably corresponds to subjects with the two diseases, i.e., DCG responsible for the parietal cel1 antibodies and MAG, the only disease known to lead to atrophy of the antrum.
summarizes the classification previously proposed by one of usa3 Classic DCG, as the pernicieus anemia syndrome, is characteristic of populations of Scandinavian and northern European extraction and is either absent or extremely rare in other groups. The second type of atrophic gastritis has historically created much confusion. It was called multifocal atrophic by Lambert in 197Z1’ and type B by Strickland and Mackay in 197X*’ The choice of the name type B turned out to be unfortunate because it has been frequently misused to describe gastritis without atrophy (not considered in the Strickland and Mackay article confined to atrophic types of gastritis) or gastritis of bacterial (B) etiology.14 Its topographic distribution has been extensively studied in its “pure” form in populations in which pernicieus anemia is not present. Its multifocal pattern has been excellently illustrated by Stemmermann and Hayashi15 who used special stains to locate the foei of intestinal metaplasia in gastrectomy specimens from Japanese patients. Its multifocal nature and its agedependency was shown in a study of over 1500 autopsy specimens of Colombian patients,16 as seen in Table 2 which includes topographic distribution of 1113 foei of metaplasia found in 435 specimens. It is clear that the focal lesions in which metaplasia is accompanied by chronic inflammatory infiltrate are more prevalent and appear earlier in the middle and lower lesser curvature (around the incisura) and spread to other areas with age. The classification problems have arisen mostly in studies of populations in which both the pernicieus anemia syndrome and MAG are frequent. There is no reason why a subject with a genotype associated with the pernicieus anemia syndrome, exposed to the environment that leads to MAG, should not develop both types of atrophic gastritis. Detailed studies of the dynamics of the gastritis have been published, especially by the Finnish group of Siurala et al. and Kekki et a1.4,‘7Their grading system clearly describes the dynamics of progression of atrophy of the corpus (a feature shared by DCG and MAG) and atrophy of the antrum (an exclusive feature of MAG).
Table 2. Distribution
OF CHRONIC GASTRITIS
Two Types of Peptic Ulcers The second major source of confusion comes from the fact that for many years gastric and duodenal peptic ulcers were considered as one nosologic entity. This led to the notion that the gastritis associated with each localization was part of the same disease complex. It seems clear now that the two peptic ulcers are different disease entities. Gastric ulcer is accompanied by MAG, whereas duodenal ulcer is accompanied by diffuse antral (not atrophic) gastritis (DAG). Ulcers of the pyloric Channel behave as duodenal ulcers in this regard.‘g~20 The existente of DAG has been recognized by many investigators, although different names or descriptions have been used. Diffuse antral gastritis involves diffusely the full thickness of the mucosa exclusively in the antrum and is characterized by a dense lymphoplas-
Metaplasia
in Stomachs
of Colombian
Subjects
Location of lesions
Age (yrl
No. of specimens with lesions
No. of lesions
9 100 125 201 435
15 171 313 614 1113
0-14 15-34 35-54 55+
Total NOTE. Parentheses
Lesser curvature
show percentage
Cardia 2 13 31 71 117
(2.2) (13.0) (24.8) (35.3)
positive for each site.
Upper 1 20 52 101 174
(1.1) (20.0) (41.6) (50.2)
Greater curvature
Medium 2 41 78 148 269
(2.2) (41.0) (62.4) (73.6)
Lower 8 76 94 165 343
(88.9) (76.0) (75.2) (82.1)
Medium
Fundus
1 16 40 94 151
1 (1.1) 5 (5.0) 18 (14.4) 35 (17.4) 59
(1.1) (16.0) (32.0) (46.7)
358
CORREA
AND YARDLEY
mocytic infiltrate. Gland loss (atrophy) and intestinal metaplasia are not part of DAG. However, as in the previous example, occasionally DAG and MAG coincide in the same patient. The evidente for DAG as an independent nosologie entity is mostly epidemiological; it is the predominant form of chronic gastritis in children and young adults, it predominates in affluent urbanized populations, it is specifically associated with duodenal or pyloric ulcers, and it does not lead to atrophy (gland loss), intestinal metaplasia, dysplasia, or gastric carcinoma. Present evidente strongly suggests that infection with H. pylori may be the chief cause of DAG, probably triggered by precipitating factors so far poorly understood. Gastric ulcer, on the other hand, is part of the MAG disease complex, multifocal in the antrum and corpus and associated with atrophy and intestinal metaplasia.lg It is associated with an increased risk of gastric carcinoma.” Schindler” recognized the differences in the gastritis of the two types of ulcer when he stated: “In gastric ulcer often atrophic changes are found. These are almost always missing in duodenal ulcer, in which hypertrophic gastric mucosal thickness predominates.” He notes that these findings were previously reported by Stempien et al. in 1953. The endoscopic “hypertrophy” of the antrum of duodenal ulcer patients led to the endoscopic classification of DAG as hypertrophic gastritis, which has been subsequently abandoned.” A totally different entity, hypertrophy of the oxyntic mucosa (without inflammation) is seen in the Zollinger-Ellison and related syndromes. H. pylori is frequently found in MAG, but its prevalente varies markedly between populations from approximately 100% in populations at high gastric cancer risk to somewhere between 50% and 70% in populations at lower gastric cancer risk.23 Superficial
Gastritis
A final point of confusion relates to the term superficial gastritis, described as an inflammatory infiltrate localized to the superficial portions of the Superficial is therefore a term gastric mucosa.3~‘2~21~24 to describe the topographic distribution of the infiltrate. The problem arose when some investigators stated that when the infiltrate penetrated to the full thickness of the mucosa, the gastritis became “atrophic.” Atrophy of course has nothing to do with the depth of the infiltrate. It has been used to imply gland loss since the times of Magnus.” The trend to confuse topography of infiltrate with loss of glands apparently began as a result of attempts to correlate endoscopic and histopathologie findings21*25but has been unfortunately adopted in more recent publica-
GASTROENTEROLOGY
Vol. 102, No. 1
tions. There is no scientific evidente that infiltrate of the full thickness of the mucosa is a cause or a consequente of gland 10ss.~~*~’ The confusion might have been an attempt to fill the vacuum created by the lack of a name for DAG, which was frequently observed by many pathologists but not recognized as a disease entity. Attempts to fill the vacuum led to a proposal to cal1 preatrophic gastritis those cases with “reduction of the parenchyma and extension of the inflammatory infiltrate into the deepest areas.” Pseudoatrophic would be a more appropriate term for this morphological expression of DAG, because the apparent reduction of the parenchyma does not represent gland loss but separation of glands to accommodate the dense infiltrate in the lamina propria. Problems of the Sydney System As described above, the main misconceptions and misunderstandings about chronic gastritis have been identified and are slowly being clarified. This trend, however, may be reversed by the Sydney system for the following reasons: (a) it confuses the need for a system of grading and reporting (useful to assess the degree and topography of specific histological changes) with the need for a classification (a systematic arrangement of nosologic entities); (b) it preserves unproven assumptions of past attempts to classify the disease entities, especially the notion that al1 forms of chronic gastritis are part of a continuum of progressive changes, from leucocytic infiltrate to gland loss and metaplasia; and (c) it ignores the wel1 known interpopulation variations in the distribution of the types of gastritis and tries to impose the present-day European experience on the rest of the world. Conclusion 1. To clarify the present confusion, grading systems have to be recognized as different from classifications. 2. There is abundant evidente that there are two separate entities associated with gastric atrophy (gland loss frequently associated with intestinal metaplasia). One is diffuse, localized to the oxyntic mucosa, and part of the pernicieus anemia syndrome; the other is multifocal in the antrum and corpus and is the predominant type in nonScandinavian populations at high gastric cancer risk. Both types cover more extensive area of the mucosa with age. 3. There is abundant evidente that the duodenal and pyloric peptic ulcers are accompanied by a chronic gastritis limited to the antrum, characterized by a diffuse, dense, and deep lymphoplasmo-
January 1992
GRADING
cytic infiltrate, and almost universally associated with severe infection by H. pylori. There is no scientific evidente that it leads to atrophy, metaplasia, or carcinoma. Diffuse antral gastritis is completely reversible after treatment; such reversibility has not been shown for MAG. 4. In some individuals, two types of gastritis may coexist. This is especially the case with MAG, which may coexist with corpora1 atrophic gastritis of the pernicieus anemia type or with the DAG of the type seen in duodenal ulcers. 5. The disease entities have been wel1 recognized, but the names given to them by different investigators are multiple and confusing. 6. Much is known about the biology of chronic gastritis, and the chief problems are those of nomenclature (semantics) and classification. In our opinion, the Sydney system has conceptual flaws that may perpetuate outmoded views and fail to help in the clarification of the present state of confusion. Further joint efforts among pathologists and other specialists wil1 be needed before a satisfactory and generally accepted system for classifying chronic gastritis can be achieved. References 1. Misiewicz JJ, Tytgat G, Goodwin CS, Price A, Sipponen P, Strickland R. The Sydney system: a new classification of gastritis. Working Party Reports of the 9th World Congress of Gastroenterology. Melbourne: Blackwell Scientific, 1989:110. 2.Gastroenterologists in Sydney-histology and Helicobacter. Lancet 1990;2:779-780. 3. Correa P. Chronic gastritis: a clinico-pathologie classification. Am J Gastroenterol 1988;83:504-509. 4. Siurala M, Sipponen P, Kekki M. Chronic gastritis: dynamics and clinical aspects. Stand J Gastroenterol 1985;2O(Suppl 109):69-76. 5. Haot J, Hamichi L, Wallez L, Mainguet P. Lymphocytic gastritis: a newly described entity: a retrospective endoscopic and histological study. Gut 1988;29:1258-1264. 6. Karttunen T, Niemela S. Lymphocytic gastritis and coeliac disease. J Clin Pathol 1990;43:436. Dixon MF, O’Connor HJ, Axon ATR, King RFJG, Johnston D. Reflux gastritis: distinct histopathological entity? J Clin Pathol 1986;39:524-530. Sobala GM, King RFG, Axon ATR, Dixon MF. Reflux gastritis in the intact stomach. J Clin Pathol 1990;43:303-306. Fenwick S. On atrophy of the stomach. Lancet 1870;2:78-80.
AND CLASSIFICATION OF CHRONIC GASTRITIS359
10.
Magnus HA. A re-assessment of the gastric lesion in pernicious anaemia. J Clin Pathol 1958;11:289-295. 11. Strickland RG, Mackay IR. A reappraisal of the nature and significante of chronic atrophic gastritis. Am J Dig Dis 1973;18:426-440. 12. Lambert R. Chronic gastritis. Digestion 1972;7:83-126. 13. Correa P. The epidemiology and pathogenesis of chronic gastritis. Three etiologic entities. Front Gastroenterol Res 1980;6:98-108. 14. Wyatt JI, Dixon MF. Chronic gastritis. A pathogenetic approach. J Pathol 1988;154:113-124. 15. Stemmermann GN, Hayashi T. Intestinal metaplasia of the gastric mucosa: a gross and microscopic study of its distribution in various disease states. J Nat1 Cancer Inst 1976;57:10271035. 16. Correa P, Cue110 C, Duque E. Carcinoma and intestinal metaplasia of the stomach in Colombian migrants. J Nat1 Cancer Inst 1970;44:297-306. 17. Kekki M, Siurala M, Varis K, Sipponen P, Sistonen P, Neolanlina HR. Classification principles and genetics of chronic gastritis. Stand J Gastroenterol 1987;22(Suppl 141):1-28. 18. Glass GBJ, Pitchumoni CS. Atrophic gastritis. Hum Pathol 1975;6:219-250. 19. Gear MWL, Truelove SC, Whitehead R. Gastric ulcer and gastritis. Gut 1971;12:639-645. 20. Stemmermann G, Haenszel W, Locke F. Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii. J Nat1 Cancer Inst 1977;58:13-20. 21. Schindler R. Gastritis. In: Paulson M, ed. Gastroenterologic medicine. Philadelphia: Lea & Febriger, 1969:687-709. 22. Cheli R, Perasso A, Giacosa A. Gastritis. A critical review. New York: Springer Verlag, 1987:115-139. 23. Correa P, Fox J, Fontham E, Ruiz B, Lin Y, Zavala D, Taylor N, Mackinley D, delima E, Portilla H, Zarama G. Helicobacter pylori and gastric carcinoma: serum antibody prevalente in populations with contrasting cancer risks. Cancer 1990; 66:2569-2574. 24. Whitehead R, Truelove SC, Gear MWL. The histological diagnosis of chronic gastritis in fiberoptic gastroscopy biopsy specimens. J Clin Pathol 1972;25:1-11. 25. Motteram R. Biopsy study of chronic gastritis and gastric atrophy. J Pathol Bacterial 1951;63:389-394. 26. Yardley JH. Pathology of chronic gastritis and duodenitis. In: Goldman H, Appelman HD, Kaufman N, eds. Gastrointestinal pathology. IAP monograph. Baltimore: Williams & Wilkins, 1990:69-143. 27. Paul1 G, Yardley JH. Pathology of C. pylori-associated gastric and esophageal lesions. In: Blaser MJ, ed. Campylobacter pylori in gastritis and peptic ulcer disease. New York: IgakuShoin, 1989:73-97. Received November 2, 1990. Accepted March 15, 1991. Address requests for reprints to: Pelayo Correa, M.D., Department of Pathology, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, Louisiana 70112.
1992;102:355-359
Grading and Classification of Chronic Gastritis: One American Response to the Sydney System PELAYO Department Department
CORREA
and JOHN H. YARDLEY
of Pathology, Louisiana State University Medical Center, New Orleans, Louisiana; and of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
A
new classification of chronic gastritis coined the Sydney system has been proposed as a “flexible matrix of rules.“‘* The system claims that “the recognition that Helicobacter pylori is the major cause of chronic inflammation of the human gastric mucosa has in part solved this problem”. As is often the case, the enthusiasm over new medical findings may have led to overinterpretation. Chronic gastritis is a multifactorial disease, and its biological characteristics are stil1 poorly understood. H. pylori is undoubtedly an important etiologic factor but not the only one. The purpose of this article is to give the reader our reasons for believing that the Sydney system has major flaws in regard to both its underlying premises about the nature of chronic gastritis and in its approach to classifying these disorders. Furthermore, we believe that those flaws are so serious that they could have a detrimental effect on progress in understanding chronic gastritis if the Sydney system becomes widely accepted. We have necessarily given our contrasting views about gastritis by reference to terminology and approaches previously reported by one of US,~but our primary purpose is not mere advocacy of one particular system. We fee1 strongly that understanding of chronic gastritis, spurred by recent exciting discoveries, continues to evolve and that its evolution should not be impeded by accepting questionable inferences on etiopathogenesis and by premature attempts to establish a universal system of classification. The Sydney System The Sydney system recommends that the diagnosis of gastritis be made by integration of information on its etiology, histopathology, and endoscopy, as shown in Figure 1. It further recommends that the same grading categories (mild, moderate, and severe) be used for histological and endoscopic variables without considering the poor record of interobserver reproducibility of such exercises. The system assumes that al1 forms of chronic gastritis are one nosologic entity, with the exception of forms with a specific etiology. It further assumes that it is a
progressive disease in which al1 types of advanced lesions, regardless of topography or morphology, are sequentia1 events of common precursors and suggests H. pylori (apparently in isolation from other etiologic factors) as the cause of the condition. The Sydney system proposes that “the microscopic details of the gastritis are documented in the main body of the pathologist’s report by a series of SUFFIX phrases, the major variables being graded using a common uniform scale. In the conclusion, the topographic summary phrase is PREFIXED, if sufficient data are available, by the etiology or by the most likely etiologic association.“’ This amounts to a grading scheme for each main area of the mucosa (antrum and corpus) prefixed by an etiologic opinion. A system of grading histological parameters by topography could indeed be the basis for a classification but is not in itself a classification, defined as a categorization of nosologic entities. The Sydney system recommends “a minimum of two biopsies from the anterior and posterior walls of the antrum and corpus” (ignoring the incisura). It thus ignores that in the multifocal atrophic gastritis (MAG) nosologic complex, the earliest and most advanced lesions are usually found in and around the incisura. The system creates new problems for the pathologists by unwisely stating that “attempts to orient biopsies are unnecessary.” The endoscopic component proposes that edema, erythema, friability, exudate, erosions, hyperrugosity, fold atrophy, visibility of vascular pattern, bleeding spots, and granularity be graded and used to classify the gastritis. The present critique addresses mostly the etiology and pathological aspects of the Sydney system, but we cannot avoid expressing disagreement with implying a correlation between pathological and endoscopic findings in chronic gastritis. The limited potential of endoscopy in classifying gastritis has been noted by many authors. The Sydney system is accompanied by a summary 0
1992 by the American Gastroenterological 0016-5085/92/$3.00
Association
356
GASTROENTEROLOGY Vol. 102. No. 1
CORREA AND YARDLEY
ETIOLOGY (prefix)
TOPOGRAPHY (core)
MORPHOLOGY (suffix) TOPOGRAPHY Pangastritis
ACUTE GASTRITIS CHRONIC GASTRITIS SPECIAL FORMS
-
Gastritis of antrum
Inflammation
Gastritis of corpus
- Activity
ETIOLOGY
+ Pangastritis
GRADED VARIABLES
- Atrophy
Descriptive terms
Intestinal metaplasia
PATHOGENIC ASSOCIATIONS
Edema Erythema Friability Exudate Flat erosion Raised erosion Nodularity
Helicobacter pylori
Gastritis of antrum
Gastritis of corpus
NONGRADED VARIABLES
I
I
Rugal hyperplasia Rugal atrophy Visibility of vascular pattern Intramural bleeding spots
Categories of endoscopic gastritis
I
P
Specific
Figure 1. The Sydney system. Severity grading: none, mild, moderate, and severe.
review of some of the classifications available and some comments on the epidemiology and natura1 history of gastritis. The latter is mostly based in the Finnish system of grading (not classifying) gastritis.4 To provide a perspective of the developments that have led to the present state of confusion, a different view of such developments is hereby offered, followed by comments on how they conflict with the Sydney system. Scope of Classification
Problems
The present dilemma concerns only the most common types of chronic gastritis, sometimes called nonspecific. There is no important controversy about the specific forms of gastritis. These refer to well-defined entities such as sarcoidosis, tuberculosis, and eosinophilic gastritis. Recently, two new specific forms of gastritis have been recognized: lymphocytic gastritis, which may be related to intestinal malabsorption syndromes,5*6 and reflux gastritis, originally described in postgastrectomy specimens and recently linked to nonsteroidal antiinflammatory drugs and other “chemical” injuries.“’
Two Types
ofAtrophic
Gastritis
Al1 major publications recognize the existence of two types of atrophic gastritis characterized by gland loss and intestinal metaplasia. First recognized was the type associated with the pernicieus anemia syndrome, limited to the oxyntic mucosa, and not usually associated with gastric ulcer but linked to a higher risk of gastric carcinoma originating in the previously metaplastic corpus mucosa. It has received a variety of names: gastric atrophy,g body atrophy,” type A,” diffuse atrophic gastritis,” and diffuse corpora1 atrophic gastritis (DCG).3 It is also referred to as autoimmune gastritis.13,14 Table 1
Table 1. Morphological Not atrophic Superficial (SG) Diffuse antral [DAG) Atrophic Diffuse corpora1 (DCG) Multifocal (MAG)
Classification
of Chronic Gastritis
GRADING AND CLASSIFICATION
January 1992
of Independent
Foei ofïntestinal
357
The problem arises when such a grading system is adopted as a classification, which the Sydney system does, thereby melding two diseases into one. Siurala et a1.4present their contribution as a system for grading, not for classifying atrophic gastritis. They refer to DCG as pernicieus anemia type and to MAG as the genera1 population type. However, they present a controversial speculation implying that the two diseases are one and the same when they state that “it is possible that the only essential differente between the pernicieus anemia type and the gastritis prevailing in the genera1 population is the dynamics, i.e., in the speed of progression of the body gastritis. . . .” Had they had experience with populations free of pernicieus anemia, they would probably have come to a different conclusion. Glass and Pitchumoni” recognized the coincidence of the two types of atrophic gastritis. They proposed the name type AB- (with negative parietal cel1 antibodies) corresponding to MAG. The type they cal1 AB+ (with parietal cel1 antibodies) probably corresponds to subjects with the two diseases, i.e., DCG responsible for the parietal cel1 antibodies and MAG, the only disease known to lead to atrophy of the antrum.
summarizes the classification previously proposed by one of usa3 Classic DCG, as the pernicieus anemia syndrome, is characteristic of populations of Scandinavian and northern European extraction and is either absent or extremely rare in other groups. The second type of atrophic gastritis has historically created much confusion. It was called multifocal atrophic by Lambert in 197Z1’ and type B by Strickland and Mackay in 197X*’ The choice of the name type B turned out to be unfortunate because it has been frequently misused to describe gastritis without atrophy (not considered in the Strickland and Mackay article confined to atrophic types of gastritis) or gastritis of bacterial (B) etiology.14 Its topographic distribution has been extensively studied in its “pure” form in populations in which pernicieus anemia is not present. Its multifocal pattern has been excellently illustrated by Stemmermann and Hayashi15 who used special stains to locate the foei of intestinal metaplasia in gastrectomy specimens from Japanese patients. Its multifocal nature and its agedependency was shown in a study of over 1500 autopsy specimens of Colombian patients,16 as seen in Table 2 which includes topographic distribution of 1113 foei of metaplasia found in 435 specimens. It is clear that the focal lesions in which metaplasia is accompanied by chronic inflammatory infiltrate are more prevalent and appear earlier in the middle and lower lesser curvature (around the incisura) and spread to other areas with age. The classification problems have arisen mostly in studies of populations in which both the pernicieus anemia syndrome and MAG are frequent. There is no reason why a subject with a genotype associated with the pernicieus anemia syndrome, exposed to the environment that leads to MAG, should not develop both types of atrophic gastritis. Detailed studies of the dynamics of the gastritis have been published, especially by the Finnish group of Siurala et al. and Kekki et a1.4,‘7Their grading system clearly describes the dynamics of progression of atrophy of the corpus (a feature shared by DCG and MAG) and atrophy of the antrum (an exclusive feature of MAG).
Table 2. Distribution
OF CHRONIC GASTRITIS
Two Types of Peptic Ulcers The second major source of confusion comes from the fact that for many years gastric and duodenal peptic ulcers were considered as one nosologic entity. This led to the notion that the gastritis associated with each localization was part of the same disease complex. It seems clear now that the two peptic ulcers are different disease entities. Gastric ulcer is accompanied by MAG, whereas duodenal ulcer is accompanied by diffuse antral (not atrophic) gastritis (DAG). Ulcers of the pyloric Channel behave as duodenal ulcers in this regard.‘g~20 The existente of DAG has been recognized by many investigators, although different names or descriptions have been used. Diffuse antral gastritis involves diffusely the full thickness of the mucosa exclusively in the antrum and is characterized by a dense lymphoplas-
Metaplasia
in Stomachs
of Colombian
Subjects
Location of lesions
Age (yrl
No. of specimens with lesions
No. of lesions
9 100 125 201 435
15 171 313 614 1113
0-14 15-34 35-54 55+
Total NOTE. Parentheses
Lesser curvature
show percentage
Cardia 2 13 31 71 117
(2.2) (13.0) (24.8) (35.3)
positive for each site.
Upper 1 20 52 101 174
(1.1) (20.0) (41.6) (50.2)
Greater curvature
Medium 2 41 78 148 269
(2.2) (41.0) (62.4) (73.6)
Lower 8 76 94 165 343
(88.9) (76.0) (75.2) (82.1)
Medium
Fundus
1 16 40 94 151
1 (1.1) 5 (5.0) 18 (14.4) 35 (17.4) 59
(1.1) (16.0) (32.0) (46.7)
358
CORREA
AND YARDLEY
mocytic infiltrate. Gland loss (atrophy) and intestinal metaplasia are not part of DAG. However, as in the previous example, occasionally DAG and MAG coincide in the same patient. The evidente for DAG as an independent nosologie entity is mostly epidemiological; it is the predominant form of chronic gastritis in children and young adults, it predominates in affluent urbanized populations, it is specifically associated with duodenal or pyloric ulcers, and it does not lead to atrophy (gland loss), intestinal metaplasia, dysplasia, or gastric carcinoma. Present evidente strongly suggests that infection with H. pylori may be the chief cause of DAG, probably triggered by precipitating factors so far poorly understood. Gastric ulcer, on the other hand, is part of the MAG disease complex, multifocal in the antrum and corpus and associated with atrophy and intestinal metaplasia.lg It is associated with an increased risk of gastric carcinoma.” Schindler” recognized the differences in the gastritis of the two types of ulcer when he stated: “In gastric ulcer often atrophic changes are found. These are almost always missing in duodenal ulcer, in which hypertrophic gastric mucosal thickness predominates.” He notes that these findings were previously reported by Stempien et al. in 1953. The endoscopic “hypertrophy” of the antrum of duodenal ulcer patients led to the endoscopic classification of DAG as hypertrophic gastritis, which has been subsequently abandoned.” A totally different entity, hypertrophy of the oxyntic mucosa (without inflammation) is seen in the Zollinger-Ellison and related syndromes. H. pylori is frequently found in MAG, but its prevalente varies markedly between populations from approximately 100% in populations at high gastric cancer risk to somewhere between 50% and 70% in populations at lower gastric cancer risk.23 Superficial
Gastritis
A final point of confusion relates to the term superficial gastritis, described as an inflammatory infiltrate localized to the superficial portions of the Superficial is therefore a term gastric mucosa.3~‘2~21~24 to describe the topographic distribution of the infiltrate. The problem arose when some investigators stated that when the infiltrate penetrated to the full thickness of the mucosa, the gastritis became “atrophic.” Atrophy of course has nothing to do with the depth of the infiltrate. It has been used to imply gland loss since the times of Magnus.” The trend to confuse topography of infiltrate with loss of glands apparently began as a result of attempts to correlate endoscopic and histopathologie findings21*25but has been unfortunately adopted in more recent publica-
GASTROENTEROLOGY
Vol. 102, No. 1
tions. There is no scientific evidente that infiltrate of the full thickness of the mucosa is a cause or a consequente of gland 10ss.~~*~’ The confusion might have been an attempt to fill the vacuum created by the lack of a name for DAG, which was frequently observed by many pathologists but not recognized as a disease entity. Attempts to fill the vacuum led to a proposal to cal1 preatrophic gastritis those cases with “reduction of the parenchyma and extension of the inflammatory infiltrate into the deepest areas.” Pseudoatrophic would be a more appropriate term for this morphological expression of DAG, because the apparent reduction of the parenchyma does not represent gland loss but separation of glands to accommodate the dense infiltrate in the lamina propria. Problems of the Sydney System As described above, the main misconceptions and misunderstandings about chronic gastritis have been identified and are slowly being clarified. This trend, however, may be reversed by the Sydney system for the following reasons: (a) it confuses the need for a system of grading and reporting (useful to assess the degree and topography of specific histological changes) with the need for a classification (a systematic arrangement of nosologic entities); (b) it preserves unproven assumptions of past attempts to classify the disease entities, especially the notion that al1 forms of chronic gastritis are part of a continuum of progressive changes, from leucocytic infiltrate to gland loss and metaplasia; and (c) it ignores the wel1 known interpopulation variations in the distribution of the types of gastritis and tries to impose the present-day European experience on the rest of the world. Conclusion 1. To clarify the present confusion, grading systems have to be recognized as different from classifications. 2. There is abundant evidente that there are two separate entities associated with gastric atrophy (gland loss frequently associated with intestinal metaplasia). One is diffuse, localized to the oxyntic mucosa, and part of the pernicieus anemia syndrome; the other is multifocal in the antrum and corpus and is the predominant type in nonScandinavian populations at high gastric cancer risk. Both types cover more extensive area of the mucosa with age. 3. There is abundant evidente that the duodenal and pyloric peptic ulcers are accompanied by a chronic gastritis limited to the antrum, characterized by a diffuse, dense, and deep lymphoplasmo-
January 1992
GRADING
cytic infiltrate, and almost universally associated with severe infection by H. pylori. There is no scientific evidente that it leads to atrophy, metaplasia, or carcinoma. Diffuse antral gastritis is completely reversible after treatment; such reversibility has not been shown for MAG. 4. In some individuals, two types of gastritis may coexist. This is especially the case with MAG, which may coexist with corpora1 atrophic gastritis of the pernicieus anemia type or with the DAG of the type seen in duodenal ulcers. 5. The disease entities have been wel1 recognized, but the names given to them by different investigators are multiple and confusing. 6. Much is known about the biology of chronic gastritis, and the chief problems are those of nomenclature (semantics) and classification. In our opinion, the Sydney system has conceptual flaws that may perpetuate outmoded views and fail to help in the clarification of the present state of confusion. Further joint efforts among pathologists and other specialists wil1 be needed before a satisfactory and generally accepted system for classifying chronic gastritis can be achieved. References 1. Misiewicz JJ, Tytgat G, Goodwin CS, Price A, Sipponen P, Strickland R. The Sydney system: a new classification of gastritis. Working Party Reports of the 9th World Congress of Gastroenterology. Melbourne: Blackwell Scientific, 1989:110. 2.Gastroenterologists in Sydney-histology and Helicobacter. Lancet 1990;2:779-780. 3. Correa P. Chronic gastritis: a clinico-pathologie classification. Am J Gastroenterol 1988;83:504-509. 4. Siurala M, Sipponen P, Kekki M. Chronic gastritis: dynamics and clinical aspects. Stand J Gastroenterol 1985;2O(Suppl 109):69-76. 5. Haot J, Hamichi L, Wallez L, Mainguet P. Lymphocytic gastritis: a newly described entity: a retrospective endoscopic and histological study. Gut 1988;29:1258-1264. 6. Karttunen T, Niemela S. Lymphocytic gastritis and coeliac disease. J Clin Pathol 1990;43:436. Dixon MF, O’Connor HJ, Axon ATR, King RFJG, Johnston D. Reflux gastritis: distinct histopathological entity? J Clin Pathol 1986;39:524-530. Sobala GM, King RFG, Axon ATR, Dixon MF. Reflux gastritis in the intact stomach. J Clin Pathol 1990;43:303-306. Fenwick S. On atrophy of the stomach. Lancet 1870;2:78-80.
AND CLASSIFICATION OF CHRONIC GASTRITIS359
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Magnus HA. A re-assessment of the gastric lesion in pernicious anaemia. J Clin Pathol 1958;11:289-295. 11. Strickland RG, Mackay IR. A reappraisal of the nature and significante of chronic atrophic gastritis. Am J Dig Dis 1973;18:426-440. 12. Lambert R. Chronic gastritis. Digestion 1972;7:83-126. 13. Correa P. The epidemiology and pathogenesis of chronic gastritis. Three etiologic entities. Front Gastroenterol Res 1980;6:98-108. 14. Wyatt JI, Dixon MF. Chronic gastritis. A pathogenetic approach. J Pathol 1988;154:113-124. 15. Stemmermann GN, Hayashi T. Intestinal metaplasia of the gastric mucosa: a gross and microscopic study of its distribution in various disease states. J Nat1 Cancer Inst 1976;57:10271035. 16. Correa P, Cue110 C, Duque E. Carcinoma and intestinal metaplasia of the stomach in Colombian migrants. J Nat1 Cancer Inst 1970;44:297-306. 17. Kekki M, Siurala M, Varis K, Sipponen P, Sistonen P, Neolanlina HR. Classification principles and genetics of chronic gastritis. Stand J Gastroenterol 1987;22(Suppl 141):1-28. 18. Glass GBJ, Pitchumoni CS. Atrophic gastritis. Hum Pathol 1975;6:219-250. 19. Gear MWL, Truelove SC, Whitehead R. Gastric ulcer and gastritis. Gut 1971;12:639-645. 20. Stemmermann G, Haenszel W, Locke F. Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii. J Nat1 Cancer Inst 1977;58:13-20. 21. Schindler R. Gastritis. In: Paulson M, ed. Gastroenterologic medicine. Philadelphia: Lea & Febriger, 1969:687-709. 22. Cheli R, Perasso A, Giacosa A. Gastritis. A critical review. New York: Springer Verlag, 1987:115-139. 23. Correa P, Fox J, Fontham E, Ruiz B, Lin Y, Zavala D, Taylor N, Mackinley D, delima E, Portilla H, Zarama G. Helicobacter pylori and gastric carcinoma: serum antibody prevalente in populations with contrasting cancer risks. Cancer 1990; 66:2569-2574. 24. Whitehead R, Truelove SC, Gear MWL. The histological diagnosis of chronic gastritis in fiberoptic gastroscopy biopsy specimens. J Clin Pathol 1972;25:1-11. 25. Motteram R. Biopsy study of chronic gastritis and gastric atrophy. J Pathol Bacterial 1951;63:389-394. 26. Yardley JH. Pathology of chronic gastritis and duodenitis. In: Goldman H, Appelman HD, Kaufman N, eds. Gastrointestinal pathology. IAP monograph. Baltimore: Williams & Wilkins, 1990:69-143. 27. Paul1 G, Yardley JH. Pathology of C. pylori-associated gastric and esophageal lesions. In: Blaser MJ, ed. Campylobacter pylori in gastritis and peptic ulcer disease. New York: IgakuShoin, 1989:73-97. Received November 2, 1990. Accepted March 15, 1991. Address requests for reprints to: Pelayo Correa, M.D., Department of Pathology, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, Louisiana 70112.
