Intestinal metaplasia and its variants in the gastric mucosa of portuguese subjects: A comparative analysis of biopsy and gastrectomy material

Original Contributions Intestinal Metaplasia and its Variants in the Gastric Mucosa of Portuguese Subjects: A Comparative Analysis of Biopsy and Gastrectomy Material SALETE SILVA, MD,* and M. I. FILIPE, PHI:), FRCPATH t The incidence and prevalence of intestinal metaplasia (IM) of three types were investigated in 1,041 endoscopic biopsy specimens collected from patients with gastric abnormalities in 1981 and 1982. Intestinal metaplasia was classified as type I (complete), type II (incomplete, sulfomucin-negative), or type III (incomplete, sulfomucin-positive). Intestinal metaplasia, found in 244 biopsy specimens (23%), was prevalent in gastric carcinoma (65%), compared with the incidence of 18.4 per cent in benign conditions. The sulfomucin-negative types I and II were more common than type III and were present in both benign conditions (98 per cent) and carcinoma (64 per cent). In contrast, type III IM was seen in only 12 per cent of IM-positive biopsy specimens, 90 per cent of which (26 of 29) were from patients with carcinoma. The high specificity of type III IM (98 per cent) might be acceptable for screening purposes, but its sensitivity of 36 per cent for gastric carcinoma is low. Two main factors would seem to account for the low sensitivity, as shown in the comparative analysis of IM types in gastrectomy specimens and the previous biopsy specimens from 93 patients: 1) sampling and 2) the association of type III IM with gastric carcinoma of the intestinal type but not with diffuse gastric carcinoma. The data thus confirm a significant relation between incomplete sulfomucin-secreting IM (type III) and gastric carcinoma of the intestinal type (P < 0.001). This variant of IM should be considered a risk factor, and its presence in a biopsy specimen should prompt close surveillance. HUM PATHOL 17:988--995, 1986.

In Portugal gastric carcinoma causes m o r e deaths than cancer of any other type in both sexes. Although the mortality rate declined after 1970, it remained high in 1980, at 28.4/100,000 inhabitants, the sixth highest rate in the world. 1,2 T h e good prognosis for early gastric cancer compared with the poor survival in advanced cases 3 makes it imperative that efforts be made to prevent and/or detect the disease in the early stages of development. It is thus important to characterize precancerous lesions, so that patients at risk can be identified and followed up carefully. Precancerous lesions in the stomach include dysplasia and intestinal metaplasia (IM). While dysplasia has been considered a morphologic marker of premalignant change in the gastric mucosa, 4,5 the role of IM in the histogenesis of gastric carcinoma is still a matter of debate. Received from the *Department of Histopathology, Sta Marta Hospital, Lisbon, Portugal, and tGuy's Hospital Medical School, London, England. Revision accepted for publication February 25, 1986. Address correspondence and reprint requests to Dr. Filipe: Department of Histopathology, Guy's Hospital Medical School, London Bridge, London SE1 9RT, England.

988

Epidemiologic and long-term prospective studies of patients with chronic gastritis and IM have provided strong evidence of a link between IM and the intestinal type o f gastric carcinoma. 6- ~ However, the fact that 1M is a common lesion, occurring in both benign and malignant conditions, has limited its potential value in the screening for the risk of gastric cancer. Recent studies have identified types of intestinal metaplasia that seem to express a more selective association with gastric carcinoma. In particular, a close relation between a variant o f IM characterized by incomplete cell differentiation and sulfomucin secretion and gastric carcinoma of the intestinal type has been suggested. 1~-17 If this is so, it may prove to be a valuable marker in screening for gastric carcinoma of the intestinal type, the prevalent type in Portugal (64.2 per cent). The aim of this investigation was to establish the prevalence of intestinal metaplasia and its variants in endoscopic biopsy and'gastrectomy specimens from Portugal, a high-risk cancer area, and to assess the value and limitations o f sulfomucin-secreting incomplete IM in the screening for gastric cancer. MATERIALSAND METHODS

Endoscopic BiopsySpecimens Endoscopic biopsy specimens were obtained from 1,041 patients with u p p e r gastrointestinal symptoms attending the endoscopy clinic at Hospitals Civis (Capuchos) Lisbon, during the period from 1981 to 1982. There were 653 men and 388 women (male-to-female ratio, 1.7) ranging in age from 20 to 86 years (details of mean age and male-to-female ratio for each gastric condition are presented in table 1). Endoscopy was performed by'different endoscopists, and biopsy specimens were taken from the antrum, body, and incisura angularis, according to disease and endoscopic findings. The antrum was the most common biopsy site (53 per cent; table I). In patients with'gastric ulcer and carcinoma, samples were taken from the lesion and adjacent mucosa, and in some patients the noninvolved mucosa farther from the lesion was also sampled. T h e n u m b e r of fragments taken varied, from two to three in the absence of lesions visible to the naked eye, to four to five in patients with gastric ulcer and up to 10 for

INTESTINALMETAPLASIAAND ITSVARIANTS[Silva& Filipe) TABLE 4. Gastric Biopsy Specimens: Patients' Age and Sex and Biopsy Site in Relation to GastricAbnormaIities

Condition Normal CG GU CA Total

No. of Specimens (%) 283(27) 478(46) 170(16) 110(11) 1,041

Patients' Age (yr)* AllPatients 48 56 55 65

PatientswithIM

60 58 56 65 28-86 (range)

Site (%)

No. of Males/ NO. of Females

A

,~'B

B

1

1.9 1.5 2.0 1.3 1.7

181(64) 354(74) 95(56) 47(43) 677(53)

68(24) 81(17) 42(25) 22(20) 213(41)

26(9) 29(6) 9(5) 21(19) 85(2)

8(3) 14(3) 24(14) t 46(4)

ABBREVIATIONS:A, antrum; MB, transitionantrum/body;B, body; I, incisuraangularis; CG, chronic gastritis; GU, gastric ulcer; CA, carcinoma; IM, intestinal metaplasia. * Mean. t Site indeterminatein 18% of the specimens.

those with gastric carcinoma. All of the biopsy specimens taken from a patient were counted as one in this study. Biopsy specimens from the gastroesophageal junction and from patients with gastric stump were not included; also eliminated from the study were superficial specimens and/or specimens that showed no gastric glandular structures, i.e., ulcer base or tumor only.

G a s t r e c t o m y Specimens

FIGURE 1, Gastric mucosa showing intestinal metaplasia, type I, with regular architecture, straight crypts lined by goblet cells secreting acid mucin, and mature nonsecreting absorptive cells between. Inset,detail and prominent brush border. [Alcian blue/periodic acid-Schiff stain, x 175. Inset, x 350.] 989

Gastrectomy specimens were obtained from patients in whom biopsies had been performed previously and who underwent surgery for gastric carcinoma (93 patients) or gastric ulcer (19 patients). Clinical and macroscopic data are presented in the Results section. T h e g a s t r e c t o m y specimens were routinely opened along the greater curve, pinned onto a cork, and placed in 10 per cent f o r m o l - s a l i n e for 24 hours. After fixation, blocks were taken from the lesion, adjacent mucosa, resection margins, and, in most cases, from a region approximately 3 cm from the lesion, usually along the lesser curve. T h e biopsy specimens were fixed in a similar manner, and all tissues were routinely processed for paraffin embedding. Sections were cut at 5 p.m and stained with hematoxylin-eosin and Alcian blue, pH 2.5/periodic acid-Schiff (AB/PAS). In addition, sections showing IM were stained with high i r o n - d i amine/Alcian blue (HID/AB), pH 2.5, to identify sialomucins (blue) and sulfomucins (brown). 18 T h r e e categories o f intestinal metaplasia were identified. 17,]9,~~ Type I (complete) IM is characterized by straight crypts and regular architecture, with m a t u r e absorptive and goblet cells, the latter secreting sialomucins. Paneth cells are present (fig. 1). The features of type II (incomplete) IM include mild glandular distortion, few or no absorptive cells, and the presence of columnar mucous cells in various stages of differentiation secreting neutral and acid sialomucins; goblet cells secrete sialomucin and, occasionally, sulfomucins. Paneth cells may not be present (fig. 2). In type III (incomplete) IM glandular architecture is distorted to varying degrees, and cell dedifferentiation is more marked than in type II. Columnar mucous cells secrete predominantly sulfomucins, and goblet cells contain sialomucins and/or sulfomucins; Paneth cells are usually absent (fig. 3). The presence of sulfomucins in goblet cells can be seen in IM of any type and is therefore not a criterion for type III IM. Sulfomucins may also be detected in sites not showing IM, such as the base o f pyloric crypts, within cysts, and, very occasionally, as a trace secretion in mucous neck cells. Transitional forms between these three principal variants, in

HUMAN PATHOLOGY

Volume 17, No. 10 (October 1986]

FIGURE 2. Left, gastric mucosa showing extensive Incomplete intestinal metaplasia, with distortion of architecture, irregular crypts lined by goblet cells, and columnar mucus-secreting cells belween. Inset, detail of columnar cells. Right, type II intestinal metaplasia is predominant in section stained with high iron diamine-Alcian blue; columnar mucus-secreting cells contain neutral mucin [unstained) and slalomucin [shades of gray). Goblet ceils secrete sialomucin and, occasionally, sulfomucin [dark gray). [Le~ Alcian blue-periodic acid-Schiff stain, x 175; inset, x 350. Right, high iron diamine-Alcian blue stain, x 700.]

were examined (table 1). Examination of the majority (46 per cent) revealed chronic gastritis, either superficial or atrophic, not associated with gastric ulcer. Gastric ulcer (endoscopic and/or morphologic criteria) and gastric carcinoma accounted for 16 and 11 per cent, respectively, of the specimens examined. A sizable proportion (27 per cent) o f the specimens from patients with dyspeptic symptoms were reported as normal. T h e term normal was used to define mucosa with no histologic abnormalities, independent of the presence or absence of small foci of IM. Abnormalities of all types, particularly chronic gastritis (74 per cent), occurred most often in the antrum. T h e antrum was also the most common site for gastric ulcer and gastric carcinoma. Gastric abnormalities were seen more often in men (male-to-female ratio, 1.7), occurring almost twice more often in men than in women among the

terms of both morphology and mucin profile, are also seefi. 21 In the gastrectomy specimens, carcinomas were classified as intestinal or diffuse, as described by Lauren. 22 These two types correspond broadly to the expanded and infiltrative growth patterns in the classification of Ming. 23 In gastric biopsy specimens no attempt was made to classify the carcinomas as intestinal or diffuse. Statistical Anarysis

We used chi-square c o n t i n g e n c y tables and Fisher's exact probability test. RESULTS

Gastric Biopsies A total o f 1,04f e n d o s c o p i c b i o p s y specimens 990

INTESTINALMETAPLASIAAND ITSVARIANTS(Silva & Filipe]

~

.

-

,,-...

,

FIGURE 3, Intestinal metaplasla, type IlL Goblet cells secrete sialomucins and/or sulfomucins, which are predominant in this case [dark gray]; the columnar mucus-secreting cells between show marked production of sulfomucin (dark gray]. Inset, detail. For comparison with the absence of sulfomucins in the columnar cells in 4ype II intestinal metaplasia, see figure 2, right]. [High iron diamine stain. • 175; inset, x 350.}

9*

~

patients with no apparent histologic abnormalities, despite dyspeptic symptoms (table 1). Incidence of Intestinal Metaplosia Intestinal metaplasia of all types was observed in 244 biopsy specimens (23 per cent) (tables 2 and 3). It was prevalent in gastric carcinoma (65%) but was found in only 18.4 per cent of specimens from patients with benign conditions. IM was found in approximately 25 per cent of the specimens of chronic gastritis and gastric ulcer but was rare in otherwise normal biopsy specimens (4.6 per cent) (table 2). Type I IM, the most common (66 per cent), was TABLE 2.

Prevalence of Intestinal Metaplasia [IM] in

Gastric BiopsySpecimens No. of Specimens Condition Normal CG GU CA Total

All

IM(%)

283 478 170 110

13(5) 118(25) 41 (24) 72(65)

1,041

244(23)

-

the prevalent type in all conditions and the only type present in the 13 IM-positive specimens in the normal group. In contrast, type III IM was seen in only 12 per cent of the IM-positive biopsy specimens. Of these specimens, 26 of 29 (90 per cent) were associated with gastric carcinoma (table 2). T h e nonsulfated incomplete type II IM was found in 21 to 25 per cent of the specimens from patients with chronic gastritis, gastric ulcer, and gastric carcinoma. It seems that the nonsulfated vartants (types I and II) are common to both benign conditions (98 per cent) and carcinoma (64 per cent) (table 3). In contrast, sulfated type III IM was seen in only 2 per cent of IM-positive specimens of chronic gastritis and gastric ulcer, compared with 36 per cent of specimens of carcinoma; this difference was highly significant (P < 0.0001; table 3).

IM Type l(~)

13(100) 88(74) 30(73) 31(43) 162(66)

II(%)

Intestinal Metaplasia in Relation to Gastric Abnormalities andAge

111(%)

0 0 28(24) 2(2) 10(25) 1(2) 1 5 ( 2 1 ) 26(36) 53(22)

Intestinal metaplasia was rarely seen in specimens from patients younger than 30 years of age; the incidence o f IM increased gradnally with age after 30 years (table 4). Analysis of the IM trend with age for each gastric abnormality reveals interesting aspects. In the

29(12)

ABBREVIATIONS:CG, chronic gastritis; GU, gastric ulcer; CA, carcinoma. 991

HUMANPATHOLOGY Volume'IL No. 10 [October '1986] TABLE 3. Incidence of Intestinal Metaplasla JIM] In Benign

Conditions and Carcinoma [Endoscopic Biopsies]

Benign Carcinoma Total"

IM, All Types

IM Types I and I1 (Nonsulfated)

IM Type I11 (Sulfated)

172 72 244

169(98%) 46(64%) 215 P < 0.0001

3(2%) 26(36%) 29

n o r m a l g r o u p , IM was not d e t e c t e d in patients younger than 40 years of age, but the incidence then increased steadily, from 3.2 per cent in the fifth decade of life to 13 per cent in patients older than 70 years of age. In comparison, the incidence of IM in gastric carcinoma was much higher for the same age groups (50 and 81 per cent, respectively). A direct relation between IM and age was not so apparent for c h r o n i c gastritis a n d gastric ulcer. In p a t i e n t s younger than 50 years of age, the incidence of IM i n c r e a s e d s h a r p l y with age in both c o n d i t i o n s , reaching a plateau with no significant differences in prevalence between patients in the sixth and seventh decades and beyond (table 4). Our observations indicate a significant relation between sulfomucin-secreting incomplete IM (type III) and gastric carcinoma (P < 0.001). In our material the high specificity of IM of this type for malignancy (98 per cent) is acceptable for screening purposes. However, the sensitivity of 36 per cent for carcinoma is low (table 3). Two main factors may account for this low sensitivity: 1) different incidences of IM in general, and of type III IM in particular, in intestinal and diffuse gastric carcinoma; a n d 2) s a m p l i n g e r r o r . T h e studies of gastrectomy specimens helped to clarify these points. Comparative Analysis of Types of Intestinal Metaplasla in Biopsy and Subsequent Gastrectomy Specimens G a s t r e c t o m y specimens f r o m 93 patients in whom carcinoma had been identified in the previous biopsy specimen (see above) were exanfined and classified as intestinal carcinoma (60 patients) or diffuse carcinoma (33 patients). 22 More than half of the gasTABLE 4.

tric carciuomas of tile intestinal type were localized in tile antrum, with the remainder equally distributed in tile antrum/body transition and body (mainly in tile lesser curve). The diffl~se carcinomas were evenly distributed in tile various regions (table 5). The male-to-female ratio (1.3) was tile same for both categories of tumor, but the mean ages for both men and women were nmch lower for diffuse carcinoma (men, 53 years; women, 48 years) than for gastric carcinoma of the intestinal type (men, 63 years; women, 69 years). When the incidence and extent of the types of IM are /:ompared in the biopsy and gastrectomy specimens, differences are apparent, more pronounced in the gastric carcinoma of the intestinal type group than in the diffuse carcinoma group, shown in table 6. In 18 per cent of cases of gastric c a r c i n o m a no IM was seen in the g a s t r e c t o m y samples examined, compared with much higher IMnegative results in the corresponding previous biopsy specimens (42 per cent), as expected from sampling error. Another factor that would seem to account for the IM-negative findings in both biopsy and gastrectomy specimens is the type of gastric carcinoma. IM was absent in nearly half of the specimens of diffuse carcinoma (45 per cent) compared with only 3 per cent of the specimens of gastric carcinoma of the intestinal type. Type III IM was found twice as frequently in the resected material (44 per cent) as in the biopsy specimens (23 per cent). No such differences were seen for types I and II IM. Intestinal metaplasia o f all types was more common in gastric carcinoma of the intestinal type than in diffuse carcinoma. However, it is interesting that the prevalences of types I and II IM were similar in gastrectomy and biopsy material in both gastric carcinoma o f the intestinal type and diffuse carcinoma. In contrast, type III IM was significantly associated with intestinal, but not diffuse, carcinoma in both gastrectomy (62 and 9 per cent, respectively) and biopsy specimens (33 and 3 per cent, respectively) (P < 0.01). For all gastric carcinomas, the prevalence of IM was greater in the adjacent mucosa, but the extent of IM was more pronounced in gastric carcinoma of the intestinal type and the lesser curve was almost ahvays involved.

Age Distribution for Gastric Abnormalities and Intestinal Metaplasia (IM] Age Group

20-29 yr

30-39 yr

40-49 yr

50-59 yr

60-69 yr

>70 yr

Condition

All

IM(%)

All

IM(%)

All

IM(%)

All

IM(%)

All

IM(%)

All

IM(%)

Normal CG GU CA All IM(%)

34 24 9 1

0(0) 2(8.3) I(I 1) 0(0) (4.4)

59 42 16 3

0(0) 7(16.6) 5(31.2) 1(33.3) (10.8)

61 94 39 12

2(3.2) 23(24.4) 11(28.2) 6(50) (20.4)

66 147 48 26

3(4.5) 32(21.7) 9(18.7) 11(42.3) (19)

33 97 35 36

4(12) 27(27.8) 9(25.9) 28(77.7) (33.8)

30 74 23 32

4(13) 27(36.4) 6(26) 26(81.2) (39.6)

ABBREVIATIONS"CG, chronic gatritis; GU, gatric ulcer; CA. carcinoma.

992

INTESTINALMETAPI.ASIAAND ITSVARIANTS[Silva& Filipe] TABLE 5. Clinical and Morphologic Data for Gastrectomy Specimens with Carcinoma and Peptic Ulcer

Histologic Category Carcinoma Intestinal Diffuse Peptic ulcer

Mean Age (yr)

Site (%)*

No. of Cases

No. of Males/ No. of Females

Males

Females

A

MB

B

60 33 19

1.3 1.3 1: 1

63 53 51t

69 48

54 40 50

21 33 0

23 26 19

0 0 26

ABBREVIATIONS:A, antrum; A/B, antrum/body;B, body; I, incisura angularis. .* Site indeterminatein a few cases. t Range, 36-64 yr.

Gastric Ulcer

T h e incidence and frequency of the three types of IM were compared in 19 gastrectomy specimens from patients with gastric ulcer and in the preceding biopsy specimens. Almost half of the ulcers were localized in the antrum, 25.5 per cent in the incisura angularis and 18.7 per cent in the body in the lesser curve. One of the patients had two ulcers in the lesser curve involving both antrum and body (table 5). There were 10 men and nine women, ranging in age from 36 to 64 years (mean, 51 years). Intestinal metaplasia was more common in the mucosa adjacent to the ulcer. In the few cases in which it was found in areas distant from the ulcer, IM was associated with chronic atrophic gastritis. In only two cases were there differences between IM-negative biopsy specimens and the gastrectomy specimens, both of which contained foci of type III IM. In the remaining 11 IM-positive cases, examination o f both biopsy a n d g a s t r e c t o m y specimens showed type I IM only. DISCUSSION

Intestinal metaplasia was a common finding in our endoscopic material (23 per cent) and was prevalent in gastric carcinoma (65 per cent). A significant relation between sulfomucin-secreting incomplete IM (type III) and gastric carcinoma (90 percent of TABLE 6. Incidence of Intestinal Metaplasia [IM] in Gastric Carcinoma*: Comparative Analysis of Biopsy Specimens and Subsequent GastrectomySpecimens

Gastric Carcinoma

IM Types (%) I § .II III No IM Total

Intestinal

Diffuse

B

G

B

G

B

G

35 23 42

38 44 18

37 33 30

35 62 3

33 3 64

46 9 45

93

60

33

ABBREVIATIONS:B, biopsy; G, gastrectomy. * Excluding carcinomasof the gastroesophagealjunction.

specimens containing type III IM were associated with gastric carcinoma) was confirmed (P < 0.0001). Types I and II, although more common than type III, were prevalent in benign conditions and showed no significant association with malignancy. These findings are comparable with those of similar studies performed in England, France, 21 Finland, 24 and of a recent study reported by Rothery and Day2s (table 7), and they strongly support the view that type III IM could play a special role in the histogenesis of intestinal gastric carcinoma. T h e increasing frequency of IM with age has often been cited as an argument against the concept of IM as a precursor of gastric carcinoma. That IM is more common in the elderly is a f a c t . 9,21,26,27 However, the incidence o f IM is consistently higher in gastric carcinoma than in benign conditions for all age groups (table 4), and in chronic gastritis and gastric ulcer the incidence of IM was constant in patients older than 50 years o f age. Observations in the normal group suggest that IM, and type I in particular, could be related to age, but in patients older than 60 years of age its presence seems to be associated with the underlying pathologic condition, irrespective of age. Furthermore 90 per cent of the specimens containing type III IM were from patients with carcinoma, irrespective of age. Sipponen et al. 27 also found significant differences in age distribution for IM in stomachs with and without carcinoma and between types of gastric carcinoma. The role of IM as a precursor of gastric carcinoma of the intestinal type has received strong support from epidemiologic research and long-term prospective studies of patients with chronic gastritis and IM, and these findings favor the concept of environmentally induced IM leading to carcinoma, a process that may take as long as 20 years. They do not however, necessarily prove the precancerous nature of IM. In none of these studies was IM typing performed. The evidence for the precancerous nature of IM has received support from the identification of IM types, characterized by incomplete cell differentiation and atypical phenotypes, sharing features with malignancy and fetal gut 2~ and the demonstration of their selective association with gastric carcinoma of the intestinal type, as shown in this and the other

993

HUMAN PATHOLOGY Volume1L No. 10 (October 1986} TABLE7. Incidence of Incomplete Sulfomucin-Secreting Intestinal Metaplasia 0ype III} in Benign Conditions and Carcinoma: Comparative Data for Endoscopic Biopsies fromVarious Studies

distribution similar to that of chronic gastritis (74 per cent) and gastric carcinoma of the intestinal type (54 per cent) in the present series and others, 21,2s consistent with the pattern o f environmentally induced Benign Conditions Carcinoma chronic g.astritis, ss Differences also exist between gastrlc carcinomas o f the intestinal and diffuse types (%) C%) (table 6). In the former, IM, and type III IM in parSipponene4 6 31 ticular, is more prevalent and more extensive, and Filipe et al.21 7 35 foci of IM are more frequent and more widespread Rothery and Day~5 2 21 Present study 2 36 than in diffuse carcinoma. Furthermore, gastric carcinoma of the intestinal type shows a predilection for the antrum, whereas diffuse gastric carcinoma does not occur in any particular location (table 5). studies referred to earlier. Further evidence is pro3. Tile results obtained in various centers in difvided by the selective presence of type III IM in preferent countries are comparable, constituting evicancerous lesions, such as adenomas, as opposed to dence of the reproducibility of both the histochenlnonneoplastic polyps 28-s~ and dysplasia, 25 its high inicai method and the interpretation of the findings cidence in first degree relatives o f gastric carcinoma (table 7). Tile observed differences are not significant patients and patients with pernicious anemia comand may be related to disparity in the prevalence of pared with age-matched control subjects, II and its certain gastric conditions, different approaches to prevalence in mucosa surrounding early gastric carpatient selection at endoscopy, biopsy sampling, and cinomas and microcarcinomas, aLs2 ethnic variations. In the interpretation of IM types, For sulfomucin-secreting incomplete IM (type .particularly type III, the existence of transitional III) to be considered a m a r k e r o f premalignant forms between the three easily recognizable variants, change in the gastric mucosa and used in patient which may be difficult to classify, must be considfollow-up evaluation, it must fulfill certain criteria~ ered. 21 Furthermore, in the cardioesophageal juncOur study revealed the following features of type III tion, it is not uncommon to find sulfomucins in coIM: lumnar mucous cells of hyperplastic epithelium in 1. In endoscopic biopsy specimens type III IM areas often, but not always, adjacent to carcinoma. shows high specificity (98 per cent) for gastric carciThe significance of this atypical hyperplasia is not yet noma, similar to that of other reports (93 to 98 per known, but we do not consider these features to be cent) and acceptable tbr screening purposes (tables 3 indicative of IM in the absence of well-formed goblet and 7). cells. Therefore, biopsy specimens from this region 2. The sensitivity, however, is low (36 per cent; were excluded from this study. The high prevalence range in other studies, of 21 to 35 per cent) (tables 3 of type III IM (15 per cent) in cardiac biopsy specand 7). Two main factors seem to be responsible for imens reported by Rothery and Day 25 may be related the low yield of IM in biopsy specimens from cases of in part to atypical hyperplasia rather than true IM. gastric carcinoma. First, IM in general, and type III 4. A gradation of changes from chronic atrophic IM in particular, is absent from a proportion of cases .gastritis through intestinal metaplasia and, finally, to o f gastric carcinoma (18 per cent), and the preval n v a s l v e c a r c i n o m a was well d o c u m e n t e d by lence is low in the diffilse type, as illustrated in table Correa. ss A similar sequence of events has not been 6, in which the yield of IM in Tbiopsy and correestablished for type III IM. Morphologically, type III sponding gastrectomy specimens'is compared. IM fulfills the criteria for dysplasia: cellular atypia, Second, sampling errors may account in part for loss of cell differentiation, and distorted mucosal arthe low sensitMty. The difficulty of sampling focal chitecture. T h e incomplete cell differentiation in lesions, such a s IM and dysplasia, is well recognized type III IM results in biochemical and functional and accounts for some of the' negative results obcharacteristics that have no normal counterpart in tained. This problem can be minimized by taking the adult gastrointestinal tract, a n d type III IM exmultiple biopsy specimens. Knowledge of the most presses oncofetal features. 2~ likely regional distribution of IM (and IM types) and T h u s , in o u r view, i n c o m p l e t e type III IM their prevalence provides guidelines for greater should be considered a form of dysplasia.-Whether it diagnostic accuracy. It is important to realize that IM has the potential to evolve to malignancy is not yet of different types is often present in various proporknown. The answer to this question can be achieved tions in the same specimen, and that type I is the only by prospective follow-up studies. Such s~udies of most frequent and extensive, while type III tends to a group of the patients reported here are being perbe less frequent and, often, focal. Furtherntore, the formed. pattern of IM distribution seems to depend on the underlying type of chronic gastritis, sa and on the loREFERENCES cation and types of gastric carcinoma, 2~ and it also differs in gastric ulcer. 14 IM in general shows a predi1. l'ereira HC, Ribeiro MC, Alexandrino PT: Gastric cancer lection for the lesser curve and the antrum, 2L25's4 a mortality. Acta Med Port 5:305, 1984 994

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21.

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