Clinicopathologic Characteristics of Gallbladder Adenomyomas and the Contribution of Macroscopic Sampling in Adenomyoma Diagnosis
Selma ŞENGIZ ERHAN1, Sevinç HALLAÇ KESER2, Mehmet ÖZER3
1Department of Pathology, University of Health Sciences, Okmeydani Education and Research Hospital, ISTANBUL, TURKEY
2Department of Pathology, University of Health Sciences, Kartal Dr. Lutfi Kirdar Education and Research Hospital, ISTANBUL, TURKEY
3Bursa Yuksek Ihtisas Education and Research Hospital, BURSA, TURKEY
Keywords: Gallbladder, Adenomyoma, Macroscopic sampling
Adenomyoma, a reactive and hamartomatous lesion of the gallbladder, is included in the differential diagnosis of several benign and
malignant lesions. Macroscopic sampling is very important in the determination of these lesions. The agreed macroscopy protocol in recent
years has been prepared by the Hepatopancreatobiliary Pathology Working Group. We aimed to evaluate the clinicopathologic properties of
adenomyoma cases in the gallbladder and the contribution of new macroscopy techniques to the diagnosis of adenomyoma in the pre-protocol
and post-protocol parts of a one-year period.
Material and Method: Two institutes were included in the study. Adenomyoma cases diagnosed in the pre-protocol and post-protocol periods
of one year duration were included in the study. Slides and demographic properties of the cases were reexamined.
Results: While adenomyoma was present in 22 of 1879 gallbladder before the protocol, it was observed in 32 of 1781 gallbladders in the
post-protocol period. 17 of the cases were male and 37 were female. The mean age of the cases was 51.8. 52% of the lesions were located in the
fundus. A gallstone was observed in 37 cases, and cholesterolosis in 14 cases. In the comparison of the two periods, the number of cases was lower
in the post-protocol period but a 0.6% increase in the diagnosis of adenomyoma was found.
Conclusion: Adenomyoma is one of the lesions of the gallbladder that should be recognized but can be easily overlooked macroscopically. When
we conducted the sampling according to the last protocol, the increase in the diagnosis of adenomyoma showed that adequate and accurate
sampling was very useful for the detection of adenomyoma in the gallbladder.
Adenomyoma is a hyperplastic lesion that is characterised by
the proliferation of Rokitansky-Aschoff sinuses originating
in the epithelial and accompanying muscular tissue 1
Lesions are subserous and the muscular layer is thickened.
The incidence is 2-5%. Most cases are diagnosed between
the ages of 50 and 60 1,2
. The symptoms are nonspecific;
however, in very few cases, abdominal pain localized to the
right upper quadrant may be the first symptom 3
Although chronic irritation is reported to be an etiological
factor, the pathogenesis of adenomyoma is controversial.
A relationship with gallstone has frequently been reported
4. It can be easily overlooked macroscopically, and the
diagnosis is generally possible microscopically 1,5.
Due to the lesions detected in the microscopic examination
but that could not be detected in the macroscopic
examination, the method and the required quantity of sampling from gallbladder material has been a subject of
debate for many years 6,7. A macroscopic evaluation
guide was prepared and the agreed macroscopy protocol
was defined by the Turkish Federation of Pathology
Societies, Hepatopancreatobiliary Pathology Working
Group for the macroscopic examination and sampling
method of the cholecystectomy materials 8. Before this
protocol, gallbladders without a peculiarity were examined
by one sample from each of the fundus, body and neck
regions in our laboratory. Prior to this protocol, a sample
of the fundus, body and neck of the gallbladder with no
peculiarity was obtained at our clinic. After this protocol,
longitudinal samples that contain the fundus, body
and neck regions with the demonstration of the whole
gallbladder wall were obtained. In this study, we aimed to
evaluate the clinicopathological properties of adenomyoma
cases which are difficult to recognize macroscopically and
the contribution of a new macroscopic technique to the
diagnostic process before and after the protocol.
The cases with an adenomyoma diagnosis in the
gallbladder with the samples taken and reported by
different pathologists were included in the retrospective
study conducted at two centres. The period covers one year
before the protocol prepared by the Hepatopancreatobiliary
Pathology Working Group (May 15, 2015-May 15, 2016)
and one year following the protocol (May 16, 2016-May 16,
2017) in both of the clinics.
While in the pre-protocol period, gallbladders without
a peculiarity were examined using one sample from
each of the fundus, body and neck regions. In the postprotocol
one year period, longitudinal samples obtained
according to the protocol and that represented the whole
area between the cystic duct surgical margin and fundus
were exemplified in at least two cassettes. Some additional
findings such as gender, age, adenomyoma localization,
gallbladder dimensions, wall thickness in the lesional area,
accompanying cholesterolosis, gallstone (single/multiple),
metaplasia and dysplasia were also evaluated.
Statistical Analysis: In the comparisons between the
categorical variables before and after the protocol, the
parameters that met the chi-square test requirement were
obtained with the chi-square test. Fisher exact test was
performed for the parameters that did not meet the chisquare
test condition. Numerical variables that represented
a normal distribution were compared with the Student-t test.
For parameters without a normal distribution, the Mann-
Whitney U-test was used. The effect of gender, gallbladder
size, and the presence of gallstones and cholesterolosis on
the wall thickness was examined with linear regression
analysis. The correlation between the wall thickness in the
adenomyoma-containing area and gallbladder size was
evaluated with the Spearman test. All the statistical analyses
were performed with SPSS 17 (SPSS Inc., Chicago, USA)
and p<0.05 was accepted as statistically significant.
A total of 3660 gallbladder materials were present in
the study period. A total of 54 adenomyoma cases were
detected, with 22 cases (1.2%) of the 1879 gallbladders in
the pre-protocol period and with 32 (1.8%) of the 1781
gallbladders in the post-protocol period. 17 of the cases
were male (31.5%) and 37 (68.5%) were female. The age
interval of the cases ranged from 31 to 73 years and the
mean age was 51.81 ± 11.16 years.
In the examination according to localization, 52 cases of
adenomyoma (96.2%) were localized in the fundus and they
were detected in one focus (Figure 1). In two cases (3.7%)
diagnosed in the post-protocol period, adenomyoma with
multifocal involvement (segmental type) including the
fundus was present (Figure 2). The distance between the cystic duct surgical margin and the fundus ranged between
3.5 and 10.5 cm in the gallbladders. The wall thickness was
over 2 mm in a total of 47 cases (87%), with 19 (86.3%)
before the protocol and 28 (87.5%) following the protocol.
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|Figure 1: Fundal type adenomyoma; thickening of the gallbladder
wall in the fundic region.
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|Figure 2: Segmental type adenomyoma; thickening of the
gallbladder wall in the body and fundic region.
There was accompanying gallstones in 37 (68.5%) of the
cases and accompanying cholesterolosis in 14 of the cases
(25.9%). All of the adenomyoma cases accompanied by
stone were fundus localized. The diameters of the gallstones
ranged between 0.1 and 2.7 cm with an average of 0.82±0.65
cm. A single gallstone was found in 9 (24.3%) cases and
multipe gallstones in 28 (75.7%) cases. A stone was not
present in one of the segmental types of adenomyoma. In
the second case in which the gallbladder was sent as opened,
it was learnt from the surgeon that a stone was present. Yet,
it was not possible to ascertain the information regarding
the properties of the gallstone.
The adenomyoma was accompanied by a cholesterol polyp
in 2 cases (3.7%), low-grade dysplasia in 2 cases (3.7%),
pyloric metaplasia in 5 cases (9.3%) (Figure 3) and intestinal
metaplasia in 3 cases (5.6%).
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|Figure 3: Fundal type adenomyoma. Cystically dilated glands
and accompanying muscle bundles on the wall of the gallbladder.
Pyloric metaplasia seen in the glandular component at the right
lower corner (H&E; x40).
When the periods before and after the protocol were
compared, there was no statistically significant difference
between the adenomyoma diagnosis rates (p=0.11) that
belong to the two periods. However, although the number
of cases in the post-protocol period was less, an increase
in the diagnosis of adenomyoma was observed at a rate of
0.6%. Segmental type adenomyoma diagnosis was present
in two of the cases, both of which were in the post-protocol
The distribution in terms of age and gender of the cases was
similar to each other in the pre-protocol and post-protocol
It was observed that the incidence of gallstone and cholesterolosis
did not change depending on gender (p=0.51 and
p=0.53, respectively). There was no significant effect of gender,
gallbladder dimension, stone and cholesterolosis presence
on the wall thickness in adenomyoma localized areas
shown in Table III (p=0.43, p=0.18, p=0.54 and p=0.49,
respectively). No significant difference was found between
the dimensions of gallbladders that contain adenomyomas
with a wall thickness of ≤ 2 mm or > 2 mm (p=0.69). No
correlation was found between wall thickness and gallbladder
dimensions (p=0.176, p=0.20). While the mean dimension
of gallbladders that have adenomyoma with a wall
thickness of ≤ 0.2 mm was 7.5 cm (7.0-9.0), this value was
7.5 cm (6.5-8.5) in gallbladders with adenomyomas with a
wall thickness of > 2 mm (25-75th percentile values).
There was no significant difference in terms of accompanying
stone and cholesterolosis rates (p>0.05) between the two
periods but there was a statistically significant difference
(p=0.03) in terms of intestinal metaplasia, pyloric
metaplasia, cholesterol polyp and low grade dysplasia
rates. These lesions were observed more often in the postprotocol
period compared to the cases which were sampled
before the protocol. The clinicopathologic findings and
quantitative parameters of the cases are summarized in
Table I, II and III.
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|Table II: Quantitative parameters in the pre-protocol and post-protocol period.
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|Table III: Results of multivariate linear regression analysis for the wall thickness in adenomyoma localized area.
The pathogenesis of gallbladder adenomyomas is still
controversial. Degenerative disease caused by intraluminal
pressure increase in the gallbladder due to an inability
of bile discharge caused by motility failure is the most
commonly accepted hypothesis 2,5,9
. Other possible
factors are thought to be gallstones, long lasting stimulation
caused by chronic inflammation, estrogenic effect and the
insufficiency of gallbladder budding in the embryonic
. As a result, epithelial intramural diverticules
called Rokitansky-Aschoff sinuses and an accompanying
hypertrophic muscular layer cause thickening of the
gallbladder wall 1
Adenomyoma is frequently seen between 50 and 60 years
of age 5. There are differences in the literature about the
incidence among men and women. While some authors
have reported that it is three times more common in
women, other authors reported similar rates in men and
women 1,5. In our study, the age range is consistent with
the literature. As adenomyomas have been reported to be two times more common in women than in men, we
believe that an estrogenic effect could have a role in the
In our study, the adenomyoma diagnosis rates we had
detected in both pre-protocol and post-protocol periods
were lower than those reported in the literature 1,2.
We included in this study only the gallbladders with
an adenomyoma diagnosis. On other gallbladders,
adenomyoma may be absent in the diagnosis. This
may lead to the assumption that this lesion was not be
adequately sampled or not sufficiently recognized by
pathologists working in the same or different departments.
In addition, the differences and discrepancies in diagnosis
and interpretation between the pathologists as regards adenomyomas in routine pathology reports may be another
Normally, the long axis of the gallbladder is about 10 cm
10. In our cases, the range of the long axis was measured
between 3.5 and 10.5 cm. In a vast majority of the healthy
population, the thickness of the gallbladder wall is not
more than 2 mm 5,10,11. 25% of the adenomyomas
incidentally detected in the cholecystectomy materials
of patients operated for other reasons such as stones and
polyps usually have a wall thickness of more than 3 mm
5. In our study, cases with wall thickness of 4 mm or more
were present, in parallel with the reports in the literature.
We could not find any report or reference that investigated
the relationship between the wall thickness and gallbladder dimension in the literature. There was no statistically
significant relationship between these two parameters in
our cases either.
Adenomyomas are divided into three groups based on
their macroscopic properties 3,4: these groups are the
fundal, segmental and diffuse types. The fundal type is
frequently localized in the fundus and called a localized
adenomyoma. In segmental adenomyomas, the gallbladder
has an appearance similar that of an hour-glass, composed
of fundal and neck compartments that have related lumens.
The wall thickness in the fundal compartment is thicker
than in the neck region due to the adenomyoma presence.
In the diffuse type, the whole gallbladder wall is thickened
2. In some references in the literature, the fundal type 3,9
is stated to be the most frequently observed adenomyoma
type. Yet, in other references, the segmental type 4,5 has
been reported as the most frequent type. In our study,
fundal type adenomyomas were observed at a high rate.
In addition, although we had some cases diagnosed with
segmental type adenomyoma, there was no case of the
diffuse type adenomyoma.
A cholecystectomy rate of 52%-78% has been reported for
cholelithiasis materials with adenomyoma 4. There exist
some hypotheses that these lesions have a predisposition
for the formation of gallstones. It has been reported that
biliary stasis in the fundal compartment plays an important
role for the lithogenic environment and therefore creates
a predisposing condition for gallstones particularly in
segmental adenomyomas 4. In our study, the adenomyoma
type in the gallstone accompanying cases was the fundal
type. Only one of the cases diagnosed with segmental
adenomyoma had a gallstone. It has been reported that
cholesterolosis may also accompany adenomyomas in
33% of the cases 4. In some studies, it is maintained that
cholesterol deposition in the gallbladder wall may cause
gallbladder dysfunction 12. This may eventually lead to
motility dysfunction and intraluminal pressure increase
which play a role in adenomyoma pathogenesis. In the
present study, the gallstone and cholesterolosis diagnosis
rates were parallel with the ones reported in the literature
Cancer is the most frequent consideration while polyps,
lipomas, adenomas, and acute and xanthogranulomatous
cholecystitis are also included in the differential diagnosis
of adenomyomas 5. Adenomyomas, defined as benign
hyperplastic lesions, do not have more neoplastic potential
than a normal gallbladder 3. However, diagnostic
confusion may arise due to their pseudoinvasive appearance
that mimics the morphology of adenocarcinoma. It has also been reported that in situ or invasive carcinomas could
emerge 13. In some studies, the carcinoma incidence
was reported to be higher especially in gallbladders that
have segmental type adenomyomas 14. These results
were observed particularly in cholelithiasis cases, which
is a well-known predisposing factor for carcinoma in the
elderly population 9. Inflammation and chronic irritation
that occur due to the gallstones that frequently accompany
segmental adenomyomas may act as the first step in the
metaplasia-dysplasia and carcinoma sequence 2. In
our study, there were no cases of gallbladder carcinoma
accompanying the adenomyoma.
The protocols required to be followed in gallbladder
sampling and microscopic examination are still very
important and they remain a subject of discussion due to
the inability of determining high grade dysplasia and even
invasive carcinomas with macroscopic evaluation 6. In
the literature, pyloric and intestinal metaplasia, low and
high grade dysplasia and early carcinoma diagnosis rate
increases are reported by longitudinal sampling between
the cystic duct surgical margin and the fundus 7,15. We
detected an increase in our adenomyoma diagnosis rates in
the post-protocol period in our study which examines the
contribution of sampling to the detection of adenomyoma.
In addition, we observed a significant increase in the
detection of intestinal, pyloric metaplasia and low grade
dysplasia that accompanied adenomyoma in the postprotocol
Conducting a longitudinal sampling between the neck
region and fundus according to the new protocol without
causing an increase in the number of cassettes and labour
rather than doing a sampling in one or two cassettes
concerning the fundus, body and neck in the pre-protocol
period can ensure evaluation of a larger amount of mucosa
and detection of higher numbers of pathology. This
method could also ensure standardization and minimize
differences and discrepancies in sampling techniques that
are dependent on individuals and vary from one individual
to another. We therefore recommend that the application
of this technique be handled attentively as in our clinics.
In conclusion, although there was no statistically significant
difference between the two periods in our study, an increase
in the diagnosis of adenomyoma has been observed
following the protocol compared to the pre-protocol
period. In addition to the increase observed in the findings
that accompany adenomyoma in the post-protocol period,
the increase in segmental type adenomyomas detected in
the post-protocol period is also noteworthy. By creating
awareness, our study may contribute to minimizing the discrepancies in the diagnosis and interpretation of
adenomyoma. We think that the post-protocol technique
can ensure standardization among pathologists in the
sampling of the gallbladder, which in return can help to
increase the detection of various pathologies as we have
observed in our study.
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