2018, Volume 34, Number 1, Page(s) 041-048
A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study
Güldal Esendağlı1, F. Göknur Akarca1, Serdar Balcı2, Asuman Argon3, Selma Şengiz Erhan4, Nesrin Turhan5, Neslihan İnce Zengin5, Sevinç Hallaç Keser6, Betül Çelik7, Tangül Bulut7, Samir Abdullazade8, Esra Erden9, Berna Savaş9, Temmuz Bostan9, Özgül Sağol10, Anıl Aysal Ağalar10, Nuray Kepil11, Yıldırım Karslıoğlu12, Armağan Günal12, Fatma Markoç13, Burcu Saka14, Gonca Özgün15, Şükrü Oğuz Özdamar16, Burak Bahadır16, Esin Kaymaz16, Emre Işık16, Semin Ayhan17, Deniz Tunçel18, Banu Özgüven Yılmaz18, Sevinç Çelik19, Tuba Karabacak20, İpek Erbarut Seven21, Çiğdem Ataizi Çelikel21, Zuhal Gücin22, Özgür Ekinci1, Gülen Akyol1
1Department of Medical Pathology, Gazi University School of Medicine, Ankara, Turkey
2Department of Medical Pathology, Ankara University Yıldırım Beyazıt School of Medicine, Ankara, Turkey
3Department of Pathology, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
4Department of Pathology, Okmeydani Training and Research Hospital, Istanbul, Turkey
5Department of Pathology, Turkiye Yuksek İhtisas Training and Research Hospital, Ankara, Turkey
6Department of Pathology, Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey
7Department of Pathology, Department of Medical Pathology, University of Health Science, Antalya Training and Research Hospital, Antalya, Turkey
8Department of Pathology, Izmir Tepecik Training and Research Hospital, Izmir, Turkey
9Department of Medical Pathology, Ankara University School of Medicine, Ankara, Turkey
10Department of Medical Pathology, Dokuz Eylül University School of Medicine, Izmir, Turkey
11Department of Medical Pathology, İstanbul University, Cerrahpaşa School of Medicine, Istanbul, Turkey
12Department of Pathology, Gülhane Training and Research Hospital, Ankara, Turkey
13Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Onkoloji Training and Research Hospital, Ankara, Turkey
14Department of Pathology, Istanbul University Medipol School of Medicine, Istanbul, Turkey
15Department of Medical Pathology, Başkent University School of Medicine, Ankara, Turkey
16Department of Medical Pathology, Bülent Ecevit University School of Medicine, Zonguldak, Turkey
17Department of Medical Pathology, Celal Bayar University School of Medicine, Manisa, Turkey
18Department of Medical Pathology, Department of Pathology, Şişli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
19Department of Medical Pathology, Bozok University School of Medicine, Yozgat, Turkey
20Department of Medical Pathology, Mersin University School of Medicine, Mersin, Turkey
21Department of Pathology, Marmara University School of Medicine, Pendik Training and Research Hospital, İstanbul, Turkey
22Department of Medical Pathology, Bezmialem Foundation University School of Medicine, İstanbul, Turkey
Keywords: Gallbladder, Cholecystectomy, Dysplasia, Neoplasia, Sampling
As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols.
Material and Method: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages.
Results: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories.
Conclusion: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.
Although resection materials of the gallbladder (cholecystectomy
specimens) are common in our daily routine,
there are certain problems with the approaches towards
the epithelial changes/lesions and the neoplasms of the
gallbladder and this issue continues to be relevant with
increasing importance. It is a question of debate which
lesions are to be reported, in which cases a new sampling
would be required and how and by what size the resection
would be performed. Besides, there is disagreement
among the observers on the differential diagnosis between
the epithelial changes in reactive/regenerative atypia or
intestinal metaplasia and low-grade dysplasia, and between
high-grade dysplasia and invasive tumours. For this
very reason, our Hepato-Pancreato-Biliary Study Group
(HPBSG) planned a multicentre study in order to assess
the rate of the epithelial gallbladder lesions in our country
and to propose microscopy and macroscopy protocols and
we collected the pathology report diagnoses of gallbladder
resection specimens from multiple centres in Turkey.
Epithelial changes/lesions and neoplasms of the gallbladder
are rarely encountered lesions1,2. However, as cholecystectomy
is a relatively common surgical procedure,
epithelial lesions of the gallbladder, as rare as they are,
may be confronted by surgical pathologists. Among the
epithelial changes/lesions of the gallbladder, one can count
metaplastic changes/lesions (antral/pyloric metaplasia,
intestinal metaplasia), benign epithelial neoplasms
(adenomas/cystadenomas), biliary intraepithelial neoplasias
(BilIN) (dysplasia/carcinoma in situ), and invasive
carcinomas2. The protocols to be followed in sampling
and microscopic examination of the gallbladder are still of paramount importance and continue to be an issue of
debate as high-grade dysplasia and even invasive carcinoma
cannot be macroscopically identified to a large extent3.
In this multicentre study conducted with the participation
of 22 institutions around Turkey that are included in the
HPBSG, 89,324 cholecystectomy specimens sampled in
various time periods from 2003 to 2016 were retrospectively
evaluated. The number of adenocarcinomas (primary
invasive carcinomas), low- and high-grade dysplasias such
as BilIN, intracholecystic neoplasms/adenomas, intestinal
metaplasias, reactive atypia, and some other lesions was
identified. As this work, which is the first step of our study,
aim to provide awareness of where we stand in terms of
gallbladder lesions and cholecystectomy sampling, only
the pathology results were evaluated where it was noticed
that each institute had their own sampling method which
usually includes three tissue samples from the gallbladder
wall without any standardized sampling criteria dedicated
to this issue. Then, the regional and countrywide incidence
rates were presented in percentages.
In the retrospective review of 89,324 cholecystectomy
specimens obtained from all centres that participated in
the study, it was found that epithelial changes/lesions were
reported in 5,293 of these specimens (6%). Of those lesions,
411 (7%) were reported as adenocarcinoma (Figure 1
49 (0.9%) as high-grade dysplasia (Figure 3
), 208 (4%)
as low-grade dysplasia (Figure 4
), 413 (7.8%) as reactive/
regenerative atypia (Figure 5
), 90 (1.7%) as neoplastic
polyp (biliary adenoma-tubular/tubulopapillary/villous), and 831 (15.6%) as intestinal metaplasia (Figure 6
remaining 3,291 lesions (63%) included primarily nonneoplastic
polypoids/hyperplastic lesions and antral/pyloric
metaplasias (Figure 7
). The differences in the findings of
the pathology laboratories showed the rates to be between
0.11%-5% for adenocarcinoma, 0.03%-5% for high-grade
dysplasia, %0.14-%16 for low-grade dysplasia, 0.12%-2.5%
for reactive/regenerative atypia, 0.03%-11% for neoplastic
polyp, and 0.05%-5% for intestinal metaplasia (Table I
and Figure 8
). Besides, in the cholecystectomy specimens
with identified intestinal metaplasia, accompanying lesions
such as low- and high-grade dysplasias (3.03%), antral metaplasia (2.65%), adenocarcinoma (1.1%) and reactive
atypia (0.12%) were also found (Table II
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|Figure 5: Reactive atypia in gallbladder epithelium nearby
intestinal metaplasia (H&E; x400).
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|Figure 8: The percentages of epithelial lesions detected in
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|Table I: The percentages of epithelial changes/lesions detected in cholecystectomy specimens
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|Table II: The percentages of accompanying epithelial lesions in the presence of intestinal metaplasia
The geographical distribution of certain important lesions
is presented in Table III. Because results from the Black Sea
Region were obtained from only one centre, specimens from
that region are relatively limited in number. According to the
available data, the highest rates of invasive adenocarcinoma
was found in the Aegean Region while the highest rate of
high-grade dysplasia was in yjr Mediterranean Region,
the highest rate of reactive atypia and intestinal metaplasia
was in the Black Sea Region, and the highest rate of biliary
adenoma was in the Central Anatolia Region.
Click Here to Zoom
|Table III: Distribution of certain major epithelial lesions by geographical regions
Various epithelial changes/lesions developing from
the gallbladder mucosa are found in cholecystectomy specimens. The spectrum of these epithelial changes/lesions
primarily included metaplastic changes, benign neoplasms
(adenomas), low- and high-grade dysplasias as BilIN and
Gallbladder carcinomas are usually incidentally detected
in cholecystectomy specimens taken out due to cholestasis
and display themselves as carcinoma in situ or carcinoma
with superficial invasion2. In our study, the rate of
primary invasive adenocarcinoma in all cholecystectomy
specimens was found to be 0.4% and this rate is reported in
the literature to be between 0.15-2.3%4-10. In addition,
the world-wide incidence, mortality, and prevalence rate
for 5 years of gallbladder cancer is reported, respectively,
to be 1.3%, 1.7%, and 06% in the GLOBOCAN Project that
establishes up-to-date estimates at the national level about
the incidence, mortality, and prevalence for major cancers
in many countries11. In our study, the prevalence rate
for 5 years for gallbladder cancer was found to be 0.5%
for Turkey and this figure is in accordance with the data
provided by GLOBOCAN.
Gallbladder dysplasia is not a frequent condition and its
incidence is reported to be 3.3% 12. However, there are
studies in the literature that claim this rate can go up to 25%
13-16. The rate of dysplasia detected in all cholecystectomy
specimens in our study, on the other hand, was 0.25%. The
number of studies in the literature that focuses on this
issue is not adequate but the rate is reported to be between
0.7-3.3% in all studies available 5-7,12. The fact that the
rate found in our study is well below the ones reported
in the literature suggests that either these pre-neoplastic
epithelial lesions could not be sampled or not recognized
enough or low-grade dysplasia was misinterpreted as
regenerative atypia. It is reported in different series that the
incidence rate of intestinal metaplasia is 10-30% among all
cholecystectomy specimens 2. A striking result in this
respect was found in a study conducted in the population
of Chile, which is known to have a relatively higher rate
of gallbladder cancer. The rate of intestinal metaplasia
detected in cholecystectomy specimens was reported in
this study to be 58.1% 17. In our study, the relevant result
was 0.9%. This figure was again below the ones reported in
the literature and it was thought that this results from the
discrepancies in routine reporting of intestinal metaplasia
in pathology reports by pathologists and/or institutions and
the non-uniformity in macroscopic sampling.
For macroscopic examination and sampling of cholecystectomy
specimens, it was recommended in the handbook of
macroscopic examination 18 prepared by the HPBSG
of the Federation of Turkish Pathology Societies in 2013
that all cholecystectomy specimens should be handled
according to the following: (i) The specimen should be
measured in three dimensions, opened on the anti-hepatic
side and the bile drained off. It should be noted whether the gallbladder has already been opened and the container in
which the specimen has been sent should be investigated
for lesions that may have come off. The specimen should
not be opened in the sink under running water. (ii) The
number, size, shape and colour of the gallstones should be
described. (iii) The mucosa should be examined thoroughly
and its appearance, yellow mottlings, and whether it has an
ulcer or a mass lesion be specified. (iv) The thickness of
the gallbladder wall should be documented based on the
thickest part of the specimen. (v) The neck (isthmic) lymph
node (so called Cattle ganglion) should meticulously
be searched for and sampled completely after being cut
into two. (iv) The surgical margin of the cystic duct and
the hepatic aspect of the gallbladder should be marked
with ink and the samples from the peritonealized surface
of the organ should be noted, and also painted with ink.
This handbook also includes recommendations on the
sampling method and the number of slices to be sampled in
cholecystectomies performed due to tumour-associated or
non-tumour-associated reasons or due to the existence of
tumour suspicion on macroscopic examination.
It is also noticed that various sampling methods are
available for the sampling of cholecystectomy specimens
in the reference books of pathology that are in current
international use. Among these are: (i) especially for the
specimens with a prediagnosis of carcinoma, draining off
the bile with the help of an injector, injecting formalin in
the bladder, leaving the specimen to be fixed in formalin
overnight and then opening and sampling; for other
specimens, sampling three pieces each from the fundus,
body, and the neck to represent the whole wall of the
gallbladder and sampling cystic duct and any lymph node
in case of any macroscopic abnormality 19; (ii) sampling
by multiple transverse sections after rolling the emptied
organ to examine the whole mucosa on a single slide,
especially for the specimens with suspicion of carcinoma
in situ or dysplasia 12; (iii) sampling by circumferential
transverse sectioning of the proximal cystic duct margin
and by one slice divided into appropriate pieces obtained
from a whole cut transverse section of the cholecystectomy
specimens without any macroscopic abnormality 20; (iv)
sampling of the fundus and neck of the gallbladder each cut
in the transverse plane and the margin of cystic duct with
fine transverse sectioning 21.
There are also several studies in our country on the
prevalence of epithelial lesions in the gallbladder mucosa.
As for dysplasia and intestinal metaplasia which are
thought to have a connection with the development of
adenocarcinoma and neoplasms, Bahadır et al. 22 detected intestinal metaplasia in 24 of the 351 gallbladders with 11
having epithelial dysplasia of varying degrees. Incidental
carcinoma was found in 4 of the 11 cases with intestinal
metaplasia and dysplasia. In their study on polypoid lesions,
Yıldırım et al. 23 detected 1 case of adenocarcinoma in
1420 cholecystectomy specimens. In a similar study by
Tunçel et al. 24, 1 adenocarcinoma was reported in 99
polypoid lesions that were found in 4,479 cholecystectomy
specimens. Koca et al. 25 reported the incidence of
carcinoma, biliary intraepithelial neoplasia and papillary
neoplasia as approximately 2%. A similar percentage was
also reported by Mazlum et al. 26. Argon et al. 27
recommend sampling a full slice longitudinally all along the
gallbladder as this method reveals the presence of a higher
number of pyloric metaplasia, intestinal metaplasia, lowgrade
dysplasia, and invasive carcinoma than the method
of sampling the fundus and the body separately. Bolat et
al. 28 stated that the routine method in their pathology
laboratory is to take three samples from cholecystectomy
specimens. They mapped and examined 75 cholecystectomy
specimens and reported that they observed an increase in
the incidence of metaplasia, dysplasia, and early carcinoma
detection when the number of samplings was increased.
The adenoma-carcinoma sequence has also been extensively
debated recently 2. Some authors claim that the adenomacarcinoma
sequence is a natural process in adenocarcinoma
development 29. There are other studies that support
this idea, stating that there is a presence of adenomatous
residue in the areas where invasive carcinoma develops
30. There are also other publications of case series where
early microcarcinoma development in the area of adenoma
was reported 31 and there are also certain studies that
focus on the adenomas with dysplasia-carcinoma in situinvasive
carcinoma development including pyloric gland
adenomas 32. However, the results obtained from a
comprehensive series study do not support this view 2.
Intestinal metaplasia has been reported to have a significant
correlation with epithelial hyperplasia and dysplasia 17.
The importance and necessity of specifying each and every
lesion encountered in the gallbladder is also another object
at issue. It seems that the diagnosis may change if new
sections are taken from the specimen when any epithelial
abnormality is seen during microscopic examination of
the cholecystectomy materials 3. Bivins et al. 33 assert
that 4 sections would be sufficient in detecting most cases
of dysplasia. Similarly, it is reported that, in cases where
dysplasia or reactive atypia is detected after the routine
sampling process, a re-sampling of up to 4 sections cut from
the re-examined gallbladder is sufficient in detecting all
important lesions and that sampling the entire gallbladder is not necessary 34. In cases of in situ carcinoma/highgrade
dysplasia where the suspicion of invasion is excluded
and the given lesions are entirely followed up, the clinical
course has been reported to be quite good 35,36. However,
criteria for both sampling and diagnosis of low-grade
lesions and for the differentiation between reactive atypia
and low-grade dysplasia have not been clearly specified yet
37. Pathologists generally feel the need for sampling new
sections and extending the investigation mostly when highand
low-grade BilIN is present. According to Renshaw
and Gould 34, consultant institutions recommend a
reexamination of the cholecystectomy specimen and
sampling of the entire gallbladder upon identification of
these lesions but this, in accordance with the aforementioned
study, is not a necessary and appropriate approach in order
to reach a definitive diagnosis. Regarding the stance of these
authors, in a short article written by Adsay et al. 3 in 2013,
it is stated that neoplastic lesions are not easily identified,
particularly in macroscopic examination of the gallbladder
samples, and the risk in the population should also be
taken into account in these terms. It is also emphasized
that the relative coexistence of epithelial lesions in the
gallbladder with neoplastic lesions should be kept in mind.
Regarding this issue, the decision taken in the consensus
meeting sponsored by Americas Hepato-Pancreato-Biliary
Association in 2015 asserts that in high incidence areas,
sampling of the routine cholecystectomy specimens should
include a minimum of three sections representing the
wall of the bladder and the cystic duct margin; and that
the specimens with dysplasia or cancer should be entirely
As proven above, there are various methods and
recommendations in the literature and reference books
for surgical pathology regarding the procedure for the
sampling of cholecystectomy specimens.
In conclusion, although the percentage of invasive
carcinoma in all cholecystectomy specimens examined in
our study is compatible with the ones in the literature, the
rates of metaplasias and neoplasms are different and also
the incidence rate of the lesions differ from one institution
to another. The major causes of this difference include the
differences in the frequency of oncological surgery among the
institutions, non-uniformity of the macroscopic sampling
protocols, geographical dissimilarities, and the differences
in the diagnoses/interpretations of the pathologists. Besides,
during the routine pathology practices, pathologists do not
feel the need for reporting some epithelial changes/lesions
identified in the cholecystectomy specimens (i.e. antral and
It is necessary for putting an end to this confusion to identify
the accurate incidence rate of the gallbladder lesions in
Turkey, design a common path for the standardisation of
reporting with uniformity in diagnosis/terminology and
to conduct more studies including different geographical
regions by developing a new standardised method of
macroscopic sampling and microscopic examination.
In accordance with the results obtained, new sampling
criteria were specified and a prospective multicentre study
has been commenced with the aim of identifying the
accurate incidence rate of gallbladder lesions, standardising
the reporting process, and promoting uniformity in the
diagnosis/terminology according to these prescribed
methods of macroscopic sampling and microscopic
CONFLICT of INTEREST
The authors declare no conflict of interest.
1) Adsay NV. Gallbladder, extrahepatic biliary tree, and ampulla,
in Sternbergs diagnostic surgical pathology, Mills SE, editor.
Philadelphia: Wolters Kluwer; 2015:1770.
2) Albores-Saavedra J, Henson DE, Klimstra DS. Benign epithelial
tumors of the gallbladder. In: AFIP atlas of tumor pathology. Fourth
series. In: Tumors of the gallbladder, extrahepatic bile ducts, and
vaterian system. Maryland: ARP Silver Spring;2015:31-50.
3) Adsay V, Saka B, Basturk O, Roa JC. Criteria for pathologic
sampling of gallbladder specimens. Am J Clin Pathol.
4) Utsumi M, Aoki H, Kunitomo T, Mushiake Y, Yasuhara I, Arata
T, Katsuda K, Tanakaya K, Takeuchi H. Evaluation of surgical
treatment for incidental gallbladder carcinoma diagnosed during
or after laparoscopic cholecystectomy: Single center results. BMC
Res Notes. 2017;10:56.
5) Patel K, Dajani K, Iype S, Chatzizacharias NA, Vickramarajah S,
Singh P, Davies S, Brais R, Liau SS, Harper S, Jah A, Praseedom RK,
Huguet EL. Incidental non-benign gallbladder histopathology
after cholecystectomy in an United Kingdom population: Need
for routine histological analysis? World J Gastrointest Surg.
6) Wrenn SM, Callas PW, Abu-Jaish W. Histopathological
examination of specimen following cholecystectomy: Are we
accepting resect and discard? Surg Endosc. 2017;31:586-93.
7) Yamamoto H, Hayakawa N, Kitagawa Y, Katohno Y, Sasaya
T, Takara D, Nagino M, Nimura Y. Unsuspected gallbladder
carcinoma after laparoscopic cholecystectomy. J Hepatobiliary
Pancreat Surg. 2005;12:391-8.
8) Tantia O, Jain M, Khanna S, Sen B. Incidental carcinoma gall
bladder during laparoscopic cholecystectomy for symptomatic
gall stone disease. Surg Endosc. 2009;23:2041-6.
9) Talreja V, Ali A, Khawaja R, Rani K, Samnani SS, Farid FN.
Surgically resected gall bladder: Is histopathology needed for all?
Surg Res Pract. 2016;2016:9319147.
10) R aziel A, Sakran N, Szold A, Sandbank J, Hershko D, Goitein D.
Adenocarcinoma of the gallbladder: Incidental finding in patients
following laparoscopic sleeve gastrectomy and cholecystectomy.
Isr Med Assoc J. 2015;17:703-6.
11) Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo
M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality
worldwide: Sources, methods and major patterns in GLOBOCAN
2012. Int J Cancer. 2015;136:E359-86.
12) Albores-Saavedra J, Henson DE, Klimstra DS. Tumors of the
gallbladder, extrahepatic bile ducts, and ampulla of Vater. Atlas
of tumor pathology. Third series, fascicle 27. Washington DC:
Armed Forces Instıtute of Pathology;2000
13) Ojeda VJ, Shilkin KB, Walters MN. Premalignant epithelial lesions
of the gall bladder: A prospective study of 120 cholecystectomy
specimens. Pathology. 1985;17:451-4.
14) Albores-Saavedra J, Alcántra-Vazquez A, Cruz-Ortiz H, Herrera-
Goepfert R. The precursor lesions of invasive gallbladder
carcinoma. Hyperplasia, atypical hyperplasia and carcinoma in
situ. Cancer. 1980;45:919-27.
15) Sasatomi E, Tokunaga O, Miyazaki K. Precancerous conditions
of gallbladder carcinoma: Overview of histopathologic
characteristics and molecular genetic findings. J Hepatobiliary
Pancreat Surg. 2000;7:556-67.
16) Y amagiwa H. Mucosal dysplasia of gallbladder: Isolated and
adjacent lesions to carcinoma. Jpn J Cancer Res. 1989;80:238-43.
17) Duarte I, Llanos O, Domke H, Harz C, Valdivieso V. Metaplasia
and precursor lesions of gallbladder carcinoma. Frequency,
distribution, and probability of detection in routine histologic
samples. Cancer. 1993;72:1878-84.
18) Patoloji Dernekleri Federasyonu, Hepato-Pankreato-Biliyer
Patoloji Çalışma Grubu; Yılmaz F, Dursun N, Bağcı P, Balcı S,
Deniz K, Sağol Ö, Özdamar Ş, Karslıoğlu Y. Safra Kesesi ve Safra
Yolları Rezeksiyon Materyallerinde Makroskopik Değerlendirme
19) R osai J. Appendix E: Guidelines for handling of most common
and important surgical specimens. In: Rosai and Ackermans
surgical pathology, Vol:2, 10th ed. St Louis: Elsevier;2011.2601.
20) Allen DC, Cameron IA, Loughrey MB. Gallbladder. In:
Histopathology specimens. Clinical, pathological and laboratory
aspects. Allen DC and Cameron IA, editors. 2nd ed. London:
21) Abraham S. Gallbladder and extrahepatic biliary system. In:
Surgical pathology dissection. An illustrated guide. Westra WH,
Hruban RH, Phelps TH, Isacson C, editors. 2nd ed. New York:
Springer; 2002. 82-83.
22) Bahadır B, Doğan Gün B, Çolak S, Kertiş G, Cömert M, Özdamar
ŞO. Safra kesesinde metaplazi, displazi ve karsinom dizgesi.
Akademik Gastroenteroloji Dergisi. 2007;6:25-9.
23) Y ıldırım M, Erkan N, Yakan S, Boz A, Vardar E. Safra Kesesi
polipleri: 33 olgunun retrospektif analizi. ADÜ Tıp Fakültesi
24) Tunçel D, Yılmaz Özgüven B, Sarı AG, Kabukçuoğlu F, Özağarı
AA, Aksu N, Battal M. Safra kesesinin polipoid lezyonları:
99 olgunun retrospektif analizi. Cukurova Medical Journal.
25) K oca SB, Dursun N, Gücin Z, Bağcı P, Sığırcı BB, Bozkurt ER.
Kolesistektomi materyalinde neoplazi insidansı ve neoplazilerin
histolojik alt tiplendirmeleri. Sözlü Sunum -15 . 21. Ulusal
Patoloji Kongresi, 16-20 Kasım 2011, İzmir.
26) Mazlum M, Dilek FH, Yener AN, Tokyol C, Aktepe F, Dilek ON.
Profile of gallbladder diseases diagnosed at Afyon Kocatepe
University: A retrospective study. Turk Patoloji Derg. 2011;27:23-30.
27) Argon A, Yağcı A, Taşlı F, Kebat T, Deniz S, Ersöz D, Erkan
N, Kitapçıoğlu G, Vardar E. Kolesistektomi materyallerinin
makroskobik örneklemesine farklı bir bakış. 22. Ulusal Patoloji
Kongresi. Sözlü bildiri özetleri (S-012). www.turkpath.org.tr/
28) Bolat F, Kayaselçuk F, Nursal TZ, Bal N, Tuncer İ.
Kolesistektomilerde örnek sayısının artırılması ile histopatolojik
bulguların korelasyonu. Türk Patoloji Dergisi. 2007;23:137-42.
29) Albores-Saavedra J, Vardaman CJ, Vuitch F. Non-neoplastic
polypoid lesions and adenomas of the gallbladder. Pathol Ann.
30) K ozuka S, Tsubone N, Yasui A, Hachisuka K. Relation of adenoma
to carcinoma in the gallbladder. Cancer. 1982;50:2226-34.
31) K ijima H, Watanabe H, Iwafuchi M, Ishihara N. Histogenesis of
gallbladder carcinoma from investigation of early carcinoma and
microcarcinoma. Acta Pathol Jpn. 1989;39:235-44.
32) Albores-Saavedra J, Chable-Montero F, Angeles-Albores
D, Schwartz A, Klimstra DS, Henson DE. Early gallbladder
carcinoma: A clinicopathologic study of 13 cases of intramucosal
carcinoma. Am J Clin Pathol. 2011;135:637-42.
33) Bivins BA, Meeker WR Jr, Weiss DL, Griffen WO Jr. Carcinoma in
situ of the gallbladder: A dilemma. South Med J. 1975;68:297-300.
34) R enshaw AA, Gould EW. Submitting the entire gallbladder in
cases of dysplasia is not justified. Am J Clin Pathol. 2012;138:374-6.
35) Dursun N, Saka B, Balci S, Bagci P, Roa JC, Araya JC, Basturk
O, Terry P, Minhas F, Ducato L, Adsay V. Biologic behavior of
gallbladder high-grade dysplasia: A long-term survival analysis of
125 cases elucidates a mostly curable disease, which is a marker of
biliary tract cancer risk in some patients (Abstract). Mod Pathol.
36) Patel K, Balci S, Saka B, Knight J, Basturk O, Sarmiento J, Roa JC,
Araya JC, Sweeney J, Terry P, Goodman M, Adsay V. Carcinoma
in-situ of the gallbladder: The SEER database perspective
(Abstract). Mod Pathol. 2014;27:452A,3A.
37) Adsay V, Roa JC, Basturk O, Torres J, Mucientes F, Del Pozo M,
Villaseca MA, Aguayo G, Bellolio ER, Araya JC, Endo B, Lee K,
Jang KT, Jang JY, Ohike N, Shimizu M, Hirabayashi K, Terris B,
Zamboni G, Reid M, Xue Y, Bedolla G, Quigley B, Krasinskas A,
Akkas G, Memis B, Klimstra D, Hruban RH, Zhu B, Van Dyke
AL, Koshiol J. Epithelial atypia in the gallbladder: Diagnosis and
classification in an international consensus study (Abstract). Mod
38) Aloia TA, Járufe N, Javle M, Maithel SK, Roa JC, Adsay V,
Coimbra FJ, Jarnagin WR. Gallbladder cancer: Expert consensus
statement. HPB (Oxford). 2015;17:681-90.
39) Hartman D, Krasinskas AM, Sasatomi E. Caveat emptor:
Submitting the entire gallbladder in cases of dysplasia is not
justified. Am J Clin Pathol. 2013;139:830.