Virchows Arch (2006) 448: 8084

DOI 10.1007/s00428-005-0068-2
ORIGINAL ARTI CLE
Klaus Dirschmid
.
Claudia Platz-Baudin
.
Manfred Stolte
Why is the hyperplastic polyp a marker for the precancerous
condition of the gastric mucosa?
Received: 28 February 2005 / Accepted: 16 August 2005 / Published online: 28 September 2005
# Springer-Verlag 2005
Abstract It is well known from the older literature that
gastric carcinomas are more likely to develop in a stomach
containing hyperplastic polyps. The reason why such a
stomach should represent a precancerous condition is,
however, largely unexplained. The aim of this study was
to determine the disorders of the gastric mucosa in which
hyperplastic polyps occur. In 244 patients with hyperplastic
polyp, in whomat least two additional biopsies each fromthe
antrum and corpus were available, gastritis was classified on
the basis of the updated Sydney System. In none of the 244
patients was the gastric mucosa found to be normal. The
most common disorder, at 51.3%, was autoimmune gastritis
of the corpus mucosa, while chronic active Helicobacter
pylori (Hp) gastritis was seen in 37.3%of the patients. Of the
patients with Hp gastritis, 56.1% had corpus-dominant Hp
gastritis. Other forms were relatively rare: when A-gastritis,
corpus-dominant Hp gastritis and any other form of Hp
gastritis were lumped together as a precancerous condition,
these changes were found in 88.6% of the patients with hy-
perplastic polyps of the stomach. In the presence of hy-
perplastic polyps of the gastric mucosa, additional biopsies
obtained from the antrum and corpus should always be
performed to obtain a basis for deciding whether to apply Hp
eradication treatment as potential carcinoma prophylaxis.
Keywords Hyperplastic polyps
.
Gastritis
.
Precancerous
condition
Introduction
Hyperplastic polyp of the gastric mucosa, the aetiopathogen-
esis of which still has not been clarified, is itself not con-
sidered to be a precancerous condition or lesion because
carcinoma develops within it only in an average of 2.1%
(range 0 to 8%) of the cases [4, 26]. From the earlier
literature, however, it is known that the detection of such a
polyp may be a marker for the risk of gastric carcinoma
developing at some other site within the stomach [23]. For
this reason, the presence of hyperplastic polyps of the stom-
ach is considered to be a precancerous condition, and ap-
propriate screening examinations are recommended. These
older data suggest that the cause of the precancerous con-
dition is to be sought in the status of the gastric mucosa in the
antrum and corpus. However, few published reports are
available of studies investigating the underlying disorder of
the gastric mucosa in patients with hyperplastic polyp, and
most of these studies stem from the period prior to the
rediscovery of Helicobacter pylori (Hp) and before the in-
troduction of the Sydney System of gastritis classification.
Based on the results of these older studies, therefore, it can
be concluded only indirectly that hyperplastic polyps very
probably occur more frequently in atrophic autoimmune
gastritis of the corpus mucosa and in Hp-induced gastritis
[8, 12, 20].
Against this background, we investigated the antral and
corpus mucosa at a distance from the polyps, with the aim
of finding answers to the following open questions:
1. In what underlying diseases of the gastric mucosa do
hyperplastic polyps develop?
2. Can these underlying diseases explain why hyperplas-
tic polyps of the stomach is a precancerous condition?
3. Can any of these underlying disorders of the gastric
mucosa be cured by treatment, with the potential for
preventing the development of a gastric carcinoma?
Patients and methods
The status of the gastric mucosa of 244 patients with
hyperplastic polyp, from whom at least two biopsies each
were obtained concomitantly fromthe antrumand corpus for
histological diagnosis, was retrospectively analysed. The
diagnosis of hyperplastic polyp was established in the en-
doscopic polypectomy specimens of 25%of the patients and
K. Dirschmid (*)
.
C. Platz-Baudin
.
M. Stolte
Institute of Pathology, Klinikum Bayreuth,
Preuschwitzer Str. 101,
95445 Bayreuth, Germany
e-mail: pathologie.klinikum-bayreuth@t-online.de
Tel.: +49-921-4005612
Fax: +49-921-4005609
in the surgical polypectomy specimen in two patients. In all
other patients, the hyperplastic polyps were diagnosed in
forceps biopsies obtained fromthe polyps. Table 1 shows the
age distribution of the patients, Table 2 the distribution of the
location of the hyperplastic polyps within the stomach, and
Table 3 the number of hyperplastic polyps per patient.
Histological methodology
The biopsy or polypectomy specimens were fixed in 10%
formalin solution, dehydrated in the usual manner, and em-
bedded in paraffin. After deparaffination, histological sec-
tions (4 m thick, at least eight sections per tissue sample)
were stained with haematoxylin and eosin and, if necessary,
with the WarthinStarry silver stain. The classification and
grading of gastritis in the antrum and corpus were based on
the updated Sydney System [6]. Corpus-dominant Hp gas-
tritis was diagnosed whenever the grade and activity of the
Hp gastritis in the corpus were at least medium grade and at
least equally as pronounced as in the antrum. A not-yet a-
trophic autoimmune gastritis of the corpus mucosa was
diagnosed on the basis of the criteria we previously pub-
lished elsewhere and which have been confirmed by other
authors [25, 28].
Results
In none of the patients with hyperplastic polyps was a
normal gastric mucosa observed. Most commonly (51.3%),
autoimmune gastritis of the corpus mucosa, mostly in the
atrophic stage, was diagnosed (see Table 4).
In 37.3% of the patients, chronic active Hp gastritis was
the most common underlying disease of the stomach in
patients with hyperplastic polyps. More than half (56.1%)
of these patients presented with corpus-dominant Hp
gastritis.
Ex-Hp gastritis was diagnosed in 8.6%, lymphocytic
gastritis in 0.8%, and Hp gastritis with additional lympho-
cytic gastritis in 0.8% of the patients. In 1.2% of the
patients, it was not possible to classify the gastritis with
certainty (see Table 4).
Analysis of the gastritis classification in relation to the
location of the hyperplastic polyps in the antrum and cor-
pus revealed no significant differences.
Discussion
On the basis of this retrospective analysis, the questions
posed above can be answered as follows:
1. The most common underlying disease of the gastric
mucosa in patients with hyperplastic polyp is autoim-
mune gastritis of the corpus mucosa and Hp gastritis, in
particular gastritis of the corpus-dominant form.
Table 1 Age distribution of the patients
Age (years) Number of patients Percent
4150 10 4.1
5160 31 12.7
6170 58 23.8
7180 98 40.2
8190 45 18.4
>90 2 0.8
Total 244 100.0
Table 2 Location of the hyperplastic gastric polyps
Location Number of patients Percent
Pylorus 5 2.1
Antrum 59 24.1
Intermediate zone 16 6.6
Corpus 125 51.2
Fundus 6 2.5
Cardia 6 2.5
Angulus 2 0.8
Multiple locations 13 5.3
Unknown 12 4.9
Total 244 100.0
Table 3 Number of hyperplastic polyps per patient
Number of polyps Number of patients Percent
1 198 81.1
2 21 8.6
3 9 3.7
4 6 2.5
5 1 0.4
>5 6 2.5
Unknown 3 1.2
Total 244 100.0
Table 4 Classification of gastritis in the corpus in patients with
hyperplastic polyp
Number of patients Percent
Chronic active Hp gastritis
Antrum dominant (43.9%) 40 16.4
Corpus dominant (56.1%) 51 20.9
Ex-Hp gastritis 21 8.6
A-gastritis
Pre-atrophic 2 0.8
Partially atrophic 48 19.7
Atrophic 75 30.8
Non-classifiable gastritis 3 1.2
Special forms
Lymphocytic gastritis 2 0.8
Mixed lymphocytic and Hp gastritis 2 0.8
Total 244 100.0
81
2. This explains why the hyperplastic polyp of the gastric
mucosa is a marker for a precancerous condition of
the stomach.
3. The second most common underlying condition of the
gastric mucosa in patients with hyperplastic polyp can
be cured by Hp eradication therapy.
That atrophic autoimmune gastritis of the corpus mucosa
is one of the possible underlying diseases in hyperplastic
polyps can be deduced indirectly from the results of three
older publications prior to the rediscovery of H. pylori and
the introduction of the Sydney System classification of
gastritis. As early as 1977, Elsborg et al. [8] described one
or several gastric mucosal polyps in 25 of 68 patients
with pernicious anaemia. In a comparison of 52 patients
with hyperplastic polyp and patients with no such polyps,
Laxen et al. [12] found atrophy of the corpus mucosa
significantly more frequently in the former. Nakano et al.
[20] reported corpus mucosal atrophy in 46 patients with
hyperplastic polyps.
Our own observation that Hp gastritis is the second most
common underlying disease in patients with hyperplastic
polyps can be deduced from several studies with small
numbers of patients.
In 35 patients with hyperplastic polyps and Hp gastritis,
Ohkusa et al. [21] diagnosed chronic active and atrophic
gastritis and observed regression of the polyps following
Hp eradication in 12 of 17 patients. Ljubicic et al. [14] also
reported regression of hyperplastic polyps following Hp
eradication treatment in 16 of 21 patients with Hp gastritis.
Following Hp eradication, regression of multiple polyps
measuring up to 2.6 cm in diameter was noted in a case
report [18].
A relevant comprehensive study has been published by
Abraham et al. [1]. In 137 out of 160 patients with hy-
perplastic polyps, biopsies taken from gastric mucosa at
some distance from the polyps in the antrum and corpus
were examined.
This study is open to criticism on a number of points
[27], for example, that the updated Sydney System was not
taken into account and there was no subclassification of the
Hp gastritis into corpus-dominant gastritis and A-gastritis
(in the pre-atrophic stage). Gastritis was reported in 85% of
these patients; however, with regard to the forms of gas-
tritis that we consider of importance in hyperplastic polyps,
the numbers cited differ considerably from our own. In the
group described by Abraham et al. [1], Hp gastritis was
found in 25% of the patients (in our case, 37.3%), and the
percentage of autoimmune gastritis differed dramatically,
with 12% of the patients in that study compared with 51.3%
in our patient population. Furthermore, in our patients with
hyperplastic polyps, no C-gastritis was found, in contrast to
Abrahams study, in which it was observed in 20% of the
patients. In our patients, hyperplastic polyps presented in the
corpus/fundus part of the stomach in 53.5% and in the an-
trum in 24.1%, compared with 29% and 60%, respectively,
in Abrahams study. Since just 50% of Abrahams patients
had polyps measuring less than 5 mm in diameter, it is pos-
sible that they had foveolar hyperplasia. This possibility is
supported by the frequent location of the polyps in the
antrum and the high percentage of C-gastritis in that study.
Furthermore, the age distribution of his patients showed a
large range of 2288 years, although hyperplastic polyps in
patients younger than 50 years is very rarein our own
group of patients, only ten cases. All these discrepancies are
difficult to explain, maybe, in part, due to genetic/environ-
mental differences or rather because of different histological
interpretation [27].
That hyperplastic polyps of the stomach is a precancer-
ous condition was already known from earlier studies. In a
follow-up study, Seifert et al. [23] detected gastric carci-
noma in 8.5% of patients with hyperplastic polypsnot in
the polyps themselves but in the gastric mucosa at some
distance away. The development of a gastric carcinoma
within a hyperplastic polyp is, in contrast, very rare [4, 22,
26, 31]. Dijkhuizen et al. [4] and Nakano et al. [20] dem-
onstrate by molecularpathological methods a certain risk
for malignancy in hyperplastic polyps.
Our results show that the most common underlying
disease in patients with hyperplastic polyps is autoimmune
gastritis of the corpus mucosa. Autoimmune gastritis has
long been considered to be a precancerous condition, admit-
tedly with a highly variable incidence of gastric carcinoma
development in follow-up investigations [30]. When hyper-
plastic polyps have been demonstrated, a diagnostic work-up
of the matrix, with additional removal of two biopsies each
from the antrum and corpus, should be carried out. If auto-
immune gastritis is diagnosed in the non-atrophic stage [25],
Hp eradication can result in a cure [19]. In the case of
advanced autoimmune gastritis, there is a need for gastric
biopsy screening examinations in addition to appropriate
substitution therapy.
Even more important is the diagnosis of the matrix for the
detection of the second most common underlying disease of
the gastric mucosa, namely, Hp gastritis.
Although, on the basis of WHO criteria, Hp infection was
already classified as definitely carcinogenic in humans in
1994 [10], the development of gastric carcinoma in under-
lying Hp infection is relatively rare, so that, initially, it is not
easy to explain why gastric carcinomas develop more fre-
quently in patients with hyperplastic polyps and Hp gastritis.
This apparent contradiction can, however, be explained on
the basis of our additional topographic grading of Hp gas-
tritis in the antrum and corpus. While corpus-dominant Hp
gastritis is relatively rareaccounting for 1417% of all Hp
infections [11, 13, 29]in our study, it was seen in more
than half of the patients with Hp gastritis. In several
retrospective studies, we found this corpus-dominant Hp
gastritis to be statistically significantly over-represented in
patients with advanced gastric carcinoma [17] and early
gastric carcinoma [15] and in first-degree relatives of pa-
tients with gastric carcinoma [16]. For this reason, this type
of gastritis has been characterised as gastritis of the gastric
cancer phenotype [24]. These retrospective studies were
initially confirmed indirectly by the fact that, in comparison
with controls with identical Hp prevalence, relatives of pa-
tients with gastric carcinoma significantly more frequently
82
have hypochlorhydria and atrophy of the gastric mucosa [7],
both factors considered to represent an increased risk for the
development of gastric carcinoma [9]. Furthermore, relatives
of patients with gastric carcinoma are found to exhibit
polymorphisms of the interleukin-1 gene family, which are
responsible for marked production of acid, which can be
seen as an explanation for the corpus-dominant Hp gastritis
[5]. In their study of a family, Carneiro et al. [2] reported on
hyperplastic polyposis and diffuse carcinoma of the stom-
ach; they described the occurrence of hyperplastic changes/
polyps in the non-neoplastic mucosa of E-cadherin mutation
carriers [3].
The significance of corpus-dominant Hp gastritis for the
development of a gastric carcinoma was confirmed by a
large prospective Japanese study [29]. In that study, the
relative risk of a gastric carcinoma developing in corpus-
dominant gastritis was 34.5, while intestinal metaplasia
(6.4) and atrophy (4.9) both represented for a much lower
risk for gastric carcinoma.
In conclusion, our study shows that hyperplastic polyps
of the stomach is a precancerous condition because of the
most common underlying diseases in these patients, name-
ly, atrophic autoimmune and Hp gastritis, in particular the
corpus-dominant Hp gastritis. Future studies will have to
show whether, in patients with hyperplastic polyp and Hp
gastritis, gastric carcinoma prophylaxis is possible through
Hp eradication.
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