ANATOMIC PATHOLOGY
Original Article
Geographic Variations in the Histologic
Characteristics of the Gastric Mucosa
C. A. RUBIO, M.D., J. JESSURUM, M.D., AND P. ALONSO DE RUIZ, M.D.
Histologic sections of 205 gastrectomy specimens, which were
obtained for benign and malignant diseases, were reviewed. All
patients were Mexican nationals. The following histologic features were recorded: intestinal metaplasia, intramucosal cysts,
ciliated gastric cells, and different types of pyloric cells ("ordinary"; with granular cytoplasm; with small cytoplasmic vacuoles;
with large cytoplasmic vacuoles; or with homogeneous "glassy"
cytoplasm). The percentage of specimens showing intestinal
metaplasia was similar in those containing gastric ulcers (42.7%)
or adenocarcinomas (50.0%). Intestinal metaplasia was decreased
in men 59 years of age or older and in women 69 years of age
or older. Diffuse-type adenocarcinoma accounted for 90% of the
gastric tumors. Only 3 of the 205 specimens (1.9%) contained
intramucosal cysts, and only 1 (0.4%) showed ciliated cells. Py-
loric cells with granular cytoplasm were observed in 21.2% of
the specimens, and pyloric cells with small cytoplasmic vacuoles
were seen in 1.9%. Pyloric cells with large vacuoles or "glassy"
cytoplasm were not found in any case. These results indicate
differences in the proportions of several histopathologic findings
in the gastric mucosa, between Mexicans and other ethnic groups
that have been investigated in previous surveys. The authors'
findings support the hypothesis that different environmental factors, acting in disparate geographic regions, may account for
dissimilarities in the histologic appearance of "normal gastric
mucosa." (Key words: Gastric neoplasms; Histology of the
stomach; Epidemiology; Peptic ulcer disease) Am J Clin Pathol
1991;96:330-333
The factors causing the geographic variations in gastric
carcinoma remain obscure. Environmental factors have
been thought to be responsible.2,5'6 Also, the dramatic decrease in the frequency of gastric carcinoma among Japanese people emigrating to Hawaii7 or to the United
States1 strongly supports the etiologic influence of environmental factors in the development of gastric carcinoma.
If the environment contributes to gastric carcinogenesis,
it is hypothetically possible that the same factors may induce nonneoplastic changes in the normal gastric mucosa
as an initial step in the series of events that lead to gastric
carcinoma. With this hypothesis in mind, we investigated
the mucosa in gastrectomy specimens from people of disparate geographic origins: Japanese people in Japan, 8
Japanese people in Hawaii,9 Norwegians,10 Swedes,"
white Americans,12 Chinese people and Chileans (unpublished), and Mexican people. The main differences demonstrated thus far have been a high frequency of intraFrom the Department of Pathology, Hospital General de Mexico
SS, cysts, ciliated metaplastic pyloric cells, and inmucosal
Universidat Autonoma de Mexico, Mexico City. Mexico.
testinal metaplasia in populations with a high incidence
Received September 5, 1990; received revised manuscript and accepted
of gastric carcinoma, and a low frequency of these hisfor publication February 28, 1991.
tologic features in populations with a relatively low inSupported by grants from the Swedish Society of Medicine and the
cidence of gastric cancer.812"16
Karolinska Institute.
Dr. Rubio is currently with the Department of Pathology, Karolinska
In a recent publication, we described various types of
Institute, Stockholm, Sweden.
pyloric
cells in the gastric mucosa of Swedish patients
Address reprint requests to Dr. Rubio: Karolinska Institutet, Box
with gastric ulcers or carcinoma." In the current study,
60500, S-10401 Stockholm, Sweden.
Wide variations in the incidence of gastric carcinoma have
been reported in different geographic regions.'"3 In Japan,
the crude rate per 100,000 men was 86.2 between 1978
and 1982 (Miyagi Prefecture), whereas only 28.0 cases
per 100,000 men in Sweden and 17.9 cases per 100,000
men in the United States were seen during the same period. 34
In Mexico, the risk for development of gastric carcinoma is considered to be low. Unfortunately, crude incidence figures on this topic are not available. However,
in 1974 the age-adjusted death rate for patients with gastric
carcinoma was 10.05 per 100,000 patients (8.3 in Mexico
City).1 In comparison, it should be noted that the ageadjusted death rates for this tumor were 68.6/100,000 in
Japan, 22.0 in Sweden, 10.2 in the United States, and 9.7
in Mexico (1965-1966). 3
330
RUBIO, JESSURUM, AND DE RUIZ
331
Histology of theGastric Mucosa
we investigated the frequency of these pyloric cell types,
as well as intramucosal cysts, ciliated metaplastic gastric
cells, and intestinal metaplasia, in Mexicans.
MATERIALS AND METHODS
Two hundred five consecutive gastrectomy specimens
were retrieved from the files of the Department of Pathology, Hospital General, Mexico City, between 1985
and 1989. All patients had surgery for a chronic peptic
ulcer (75 gastric and 102 duodenal) or a gastric adenocarcinoma (28 patients).
Five or more sections (measuring more than 4 cm in
length) were available from the lesser curvature of the
antral region, the gastric body, the surgical margins, and
the lesion itself (peptic ulcer or adenocarcinoma). Seven
histologic features were investigated: intestinal metaplasia,16 intramucosal cysts,15 ciliated pyloric cells,13 pyloric
cells with small vacuoles or large vacuoles17 or eosinophilic
granules, and pyloric cells with nonvacuolated, homogeneous ("glassy") cytoplasm."
RESULTS
Age, Sex, and Gastric Lesions
Tissue from men constituted 61.9% (127 cases) and
that from women constituted 38.1% (28 cases) of the total
material. Similar percentages were recorded in male
(26.8%) and female (26.9%) elderly patients (older than
60 years).
Patients in the latter category had a similar percentage
of gastric ulcers, regardless of gender (15 of 46 men [32.5%]
and 10 of 29 women [34.4%]). In those with duodenal
ulcers, the percentage of elderly patients was lower among
men (14 of 72 cases [19.5%]) than among women (10 of
30 [33.3%]). In patients with adenocarcinoma, the percentage of elderly patients was higher among men (4 of
13 [30.8%] than among women (2 of 15 [16.6%].).
Age, Sex, Intestinal Metaplasia, and Lesional Type
Intestinal metaplasia was recorded in 70 of the 205
specimens (34.1%). The results indicate that the highest
percentage of men with intestinal metaplasia occurred in
those between the ages of 50 and 59 years (44.7%) and
decreased significantly after age 60. For women, the highest percentage of intestinal metaplasia was found in those
between the ages of 60 and 69 years, and decreased at
older ages.
Intestinal metaplasia was present in 32 of the 75 gastric
ulcer cases (42.7%), 24 of 102 with duodenal ulcers
(23.5%), and 14 of 28 adenocarcinoma cases (50%) (2 of
3 adenocarcinomas of intestinal type and 12 of 25 of the
diffuse type).
Intramucosal Cysts
Only 3 of 205 specimens (1.9%) had intramucosal cysts;
1 lesion occurred in a 35-year-old man with gastric ulcer,
1 was seen in a 55-year-old patient who also had a peptic
ulcer, and the third occurred in a 64-year-old woman with
adenocarcinoma. In two cases, only single cysts were
found. In the third, a group of cysts was observed in the
mucosa of the antral region (Fig. 1).
Ciliated Metaplasia
Ciliated metaplastic cells were present in only one
specimen (0.4%) (Fig. 2). These cells covered three of eight
intramucosal cysts present in the antral mucosa (see
above).
Pyloric Cells with Granular Cytoplasm
Results shown in Table 1 indicate that 27 of 127 gastrectomies (21.2%) had pyloric cells with granular cytoplasm (Fig. 3)—in addition to "ordinary" pyloric cells
(i.e., with basally located nuclei and bubbly inconspicuous
cytoplasm, sometimes with a tenuous basophilic network).
The table also shows that the presence of pyloric cells with
granular cytoplasm was similar among elderly patients—
29.6% for men and 25.0% for women.
Pyloric Cells with Small Cytoplasmic Vacuoles
Pyloric cells with small cytoplasmic vacuoles were
found in three patients (1.9%); one case occurred in a 37year-old man with a gastric ulcer, another in a 41-yearold woman with a duodenal ulcer, and the third in a 66year-old woman with adenocarcinoma.
Pyloric cells with large vacuoles or "glassy" cytoplasm
were not present.
DISCUSSION
When the results of this survey of Mexican patients
are compared with previous analyses of other ethnic
groups,9"16 several conclusions may be drawn. Roughly
one-third of the Mexican specimens contained intestinal
metaplasia. This figure is much lower than the 100%
figure quoted in a study of 223 specimens from Japanese,14
Hawaiian,18 Norwegian (unpublished), and Swedish patients.16 It should be pointed out that, in both the Japanese
and Swedish material, sections from the entire resected
stomach were available for review, whereas in the current
study we usually had only five large sections. On the other
hand, at least one of the sections reviewed in this study
was taken from the lesser gastric curvature. This is important, considering that the latter region is the zone of
predilection for gastric intestinal metaplasia. 2,31419 It
would thus appear that intestinal metaplasia may be less
frequent among Mexicans than other ethnic groups.
Only 10.7% of the adenocarcinomas in this series were
Vol. 96 •No. 3
332
ANATOMIC PATHOLOGY
Original Article
FIG. 1 (upper, left). Gastric mucosa showing intramucosal cysts. Hematoxylin and eosin (X100).
FIG. 2 (lower). Gastric cysts containing ciliated cells.
Hematoxylin and eosin (X 1,000).
FIG. 3 (right). Pyloric cells with eosinophilic cytoplasmic granules. Hematoxylin and eosin (X250).
of intestinal type, with the remaining 89.3% being of the
diffuse type. This observation has been validated in previous studies performed at our hospital.20 The low proportion of intestinal-type adenocarcinomas contrasts with
a much higher frequency in other populations: 56.3%
among Japanese,21 52.3% among Swedes,19 and 75% in
other high-risk populations.22 Thus, the low frequency of
this tumor variant in Mexicans appears to correlate well
with a low frequency of intestinal metaplasia.
Intramucosal gastric cysts also have been considered to
be one of several premalignant histologic markers in the
gastric mucosa. 815 In the current study, the number of
specimens with intramucosal cysts was very small, contrasting with the frequency of intramucosal cysts found
in Japanese15 and Swedish subjects." In 51 gastrectomy
specimens from Swedish patients, a mean of 0.9 cysts/
cm gastric mucosa (standard deviation [SD] ± 0.9) was
present. In 102 gastrectomy specimens from Japanese patients, a mean of 3.4 intramucosal cysts/cm mucosa (SD
± 6.6) was recorded. The highest frequency of intramucosal cysts (mean, 9.4 cysts/cm gastric mucosa) was found
in Japanese patients with adenomas or early gastric
cancer.15
Only 1 of the 205 patients in the current study (0.4%)
had ciliated metaplastic pyloric cells. This differs from the
figure of 35.2% cells found in 127 gastrectomy specimens
from Japanese subjects living in Japan 13 and from a frequency of 41.1% in 129 gastrectomy specimens from Hawaiian residents (including Japanese).18 The causes responsible for the low frequency of ciliated metaplastic
A.J.C.P. • September 1991
RUBIO, JESSURUM, AND DE RUIZ
333
Histology of the Gastric Mucosa
TABLE 1. THE AGE AND SEX DISTRIBUTION IN 47
GASTRIC SPECIMENS HAVING PYLORIC CELLS
WITH EOSINOPHILIC GRANULES
Number (%)
Age
(years)
10-19
20-29
30-39
40-49
50-59
60-69
70-79
>80
All ages
Male
Female
All
1 (3.7%)
3(11.1%)
5(18.5%)
10(37.0%)
6 (22.2%)
2 (7.4%)
—
6 (30.0%)
3(15.0%)
6 (30.0%)
4 (20.0%)
1 (5.0%)
1
9
8
16
10
3
—
—
—
27(100.0%)
20(100.0%)
47
cells in Mexicans and the high frequency of these cells
among Japanese and Hawaiian residents remain unknown
at present, but environmental factors may be involved in
this process.2,5"716
More than 21 % of the Mexican specimens contained
pyloric cells with eosinophilic cytoplasmic granules. This
high frequency contrasts with a much lower proportion
(5%) found in Swedish subjects." By immunohistochemical studies, these granules have been shown to contain
lysozyme." The reasons for the high frequency of pyloric
cells with lysozyme-rich granulated cytoplasm in Mexicans are unclear.
Pyloric cells with small cytoplasmic vacuoles were detected in 1.9% of our cases. In a review of Swedish patients," 12% of gastrectomy specimens had similar cells.
The vacuoles had negative findings for mucin. Since our
original description was published,17 these cells have been
the subject of research by several other investigators.23,24
Those studies indicate that the vacuoles contain fat and
not mucin. 24
In the current study, pyloric cells with large cytoplasmic
vacuoles or "glassy" cytoplasm were not found. These
types of pyloric cells are present in the gastric mucosa of
Swedish," Hawaiian (authors' unpublished data), and
Spanish subjects (authors' unpublished observations).
Thus, our investigation points out differences between
Mexicans and other ethnic groups in the frequencies of
several histologic findings in the gastric mucosa. It is conceivable that this difference may mirror variations in the
environment (including the diet) as they influence the
gastric mucosa. The possible relationship between the frequency of the histologic features we investigated and the
different incidences of peptic ulcer or carcinoma in disparate geographic areas is being explored further.
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