Dibacakan tanggal :

Pembimbing,

Case Report
dr. H. Soekimin, Sp. PA (K)

ADENOCARCINOMA OF GALLBLADDER
dr., M.Ked (PA), Sp. PA(K).

Oleh:
dr. Masriana

Pembimbing:
dr. H. Soekimin, Sp.PA (K)

DEPARTEMEN PATOLOGI ANATOMIK

FAKULTAS KEDOKTERAN
UNIVERSITAS SUMATERA UTARA
MEDAN
2023
 ADENOCARCINOMA OF GALLBLADDER
Masriana, Soekimin
Departemen Patologi Anatomik, Fakultas Kedokteran
Universitas Sumatera Utara

Abstrak
Latar Belakang: Adenocarcinoma of gallbladder adalah neoplasma epitel ganas
yang timbul di gallbladder dari epitel bilier. Lokasi tersering adalah fundus (60%)
diikuti body (30%) dan neck (10%). Kebanyakan tumor berbentuk datar, dengan
tumpang tindih yang luas pada berbagai bagian gallbladder.

Deskripsi Kasus: Dilaporkan sebuah kasus dari seorang laki-laki usia 52 tahun
datang ke RSU dengan keluhan nyeri perut kanan atas. Kemudian dilakukan
pemeriksaan histopatologi. Gambaran makroskopis diterima satu potong jaringan
dari gall bladder, berukuran 7 x 5 x 4 cm, konsistensi kenyal. Pada pemeriksaan
mikroskopis, Sediaan jaringan dari gallbladder, terdiri dari proliferasi kelenjar
dengan lumen bentuk tubular, angulated dan sebagian berdilatasi kistik yang
tersusun back to back dan sebagian kelenjar berfusi dari lapisan mukosa hingga
muskularis. Kelenjar dengan pelapis sel-sel epitel dengan inti membesar, bentuk
bulat dan oval, membran inti irreguler, kromatin kasar sebagian hiperkromatik,
anak inti dijumpai, sitoplasma eosinofilik pucat sebagian jernih. Stroma terdiri dari
jaringan ikat fibrous dengan infiltrasi sedang sel sel radang limfosit serta perdarahan
interstitial. Pembuluh darah dilatasi dan kongesti. Tidak dijumpai invasi sel-sel
tumor ke pembuluh darah dan perineural.

Diskusi dan Simpulan: Berdasarkan pemeriksaan makroskopis dan mikroskopis

kasus ini didiagnosis sebagai adenocarcinoma NOS dengan ICD-O codes : 8140/3,
topography morphology: C23.9.

Kata Kunci: Adenocarcinoma, gallbladder, cancer.

1
 ADENOCARCINOMA OF GALLBLADDER
Masriana, Soekimin
Departemen Patologi Anatomik, Fakultas Kedokteran
Universitas Sumatera Utara

Abstract:
Introduction: Carcinoma of the gallbladder is a malignant epithelial neoplasm arising in
the gallbladder from biliary epithelium.1 The most common site is the fundus (60%)
followed by the body (30%) and neck (10%). Most tumours are flat, with extensive overlap
into different sections of the gallbladder.

Case Description: A case was reported of a 52 year old men who came to the
hospital with complaints upper right abdominal pain. Then a histopathological
examination was carried out. The macroscopic image was obtained from a piece of
tissue from the gallbladder, measuring 7 x 5 x 4 cm, rubbery consistency. On
microscopic examination, the tissue preparations from the gallbladder consist of
proliferation of glands with tubular, angulated and partially dilated cystic lumens
arranged back to back and some of the glands are fused from the mucosal layer to
the muscularis. Glands lined with epithelial cells with enlarged nuclei, round and
oval in shape, irregular nuclear membrane, coarse chromatin, some
hyperchromatic, small nuclei found, pale eosinophilic cytoplasm, some clear. The
stroma consists of fibrous connective tissue with moderate infiltration of
inflammatory cells with lymphocytes and interstitial hemorrhage. Blood vessels are
dilated and congested. There was no cells into blood lymphovasvular invasion and
perineural invasion.

Discussion and Conclusion: Based on clinical and microscopic examination this

case was diagnosed as adenocarcinoma NOS with ICD-O codes : 8140/3,
topography morphology: C23.9
.
Key Words: Adenocarcinoma, gallbladder, cancer.

2
INTRODUCTION

Gallbladder cancer is the 22nd most prevalent and 17th most deadly cancer

worldwide.1,2,3 It is noted to disproportionately affect females more than males,

perhaps due to the higher propensity of females to have gallstone disease.4 The

incidence of gallbladder cancer is characterized by marked geographic and ethnic

variations; there is high to moderate incidence in India, especially northeast and

central India, South America (Chile, Bolivia, Colombia), East Asia (Korea, Japan,

China), and central Europe (Slovakia, Poland, Czech Republic).5

Gallbladder carcinoma is the most common cancer of the biliary system. It

is challenging to diagnose because patients are often asymptomatic or present with

nonspecific symptoms that mimic common benign diseases. Surgical excision is the

only curative therapy and is best accomplished at early non–locally advanced stages.

Unfortunately, gallbladder cancer often manifests at late locally advanced stages,

precluding cure. Early tumors are often incidentally detected at imaging or at

cholecystectomy performed for another indication.6

Adenocarcinomas of the gallbladder are highly malignant tumors with a

dismal prognosis, and clinicopathological and molecular research on their

pathogenesis and carcinogenesis is extremely important. According to the American

Joint Committee on Cancer, survival of gallbladder adenocarcinoma is based on the

staging of the disease, with an 80% five-year survival rate in patients with stage 0

carcinoma in situ lesions and 2% in those with stage 4b disease.7,8

As in most epithelial cancers, the development of gallbladder

adenocarcinoma is preceded by a variety of precancerous changes. However,

compared to other organs, such as colon, uterus, prostate, and pancreas, knowledge

3
of the precursor lesions of gallbladder carcinoma is limited, and their

clinicopathologic features are insufficiently characterized. This is partly due to the

rarity of these lesions, controversies about the criteria for diagnosis, and the use of

several ununified terms when referring to the lesions.9

CASE REPORT

A case was reported of a 52 year old men who came to the hospital with

complaints upper right abdominal pain. Then a histopathological examination was

carried out. The macroscopic image was obtained from a piece of tissue from the

gallbladder, measuring 7 x 5 x 4 cm, rubbery consistency. On microscopic

examination, the tissue preparations from the gallbladder consist of proliferation

of glands with tubular, angulated and partially dilated cystic lumens arranged back

to back and some of the glands are fused from the mucosal layer to the muscularis.

Glands lined with epithelial cells with enlarged nuclei, round and oval in shape,

irregular nuclear membrane, coarse chromatin, some hyperchromatic, small nuclei

found, pale eosinophilic cytoplasm, some clear. The stroma consists of fibrous

connective tissue with moderate infiltration of inflammatory cells with

lymphocytes and interstitial hemorrhage. Blood vessels are dilated and congested.

There was no cells into blood lymphovasvular invasion and perineural invasion.

4
 Fig 1. Tissue macroscopy is labeled with the PA code 631/H/23.

Fig 2. Proliferation of glands with tubular, angulated and partially dilated cystic lumens
arranged back to back (H&E 40X)

5
 Fig. 3. Proliferation partially dilated cystic lumens. (H&E 100X)

Fig. 4. Proliferation of glands with tubular, some of the glands are fused from
the mucosal layer to the muscularis. (H&E 40X).

6
 Fig. 5. Glands lined with epithelial cells with enlarged nuclei, round and oval in shape,
irregular nuclear membrane, coarse chromatin, some hyperchromatic, small nuclei found,
pale eosinophilic cytoplasm, some clear (H&E 400X)

Fig. 6. Glands lined with epithelial cells with enlarged nuclei, round and oval in shape,
irregular nuclear membrane, coarse chromatin, some hyperchromatic, small nuclei found, pale
eosinophilic cytoplasm, some clear (H&E 400X)

7
 Fig.7. The stroma consists of fibrous connective tissue with moderate infiltration
of inflammatory cells with lymphocytes(H&E 40x)

Based on clinical and microscopic examination this case was diagnosed as

adenocarcinoma NOS with ICD-O codes : 8140/3, topography morphology:

C23.9.

DISCUSSION

Gallbladder cancer is the 22nd most prevalent and 17th most deadly cancer

worldwide.1,2,3 It is noted to disproportionately affect females more than males,

perhaps due to the higher propensity of females to have gallstone disease.4 The

incidence of gallbladder cancer is characterized by marked geographic and ethnic

variations; there is high to moderate incidence in India, especially northeast and

central India, South America (Chile, Bolivia, Colombia), East Asia (Korea, Japan,

China), and central Europe (Slovakia, Poland, Czech Republic).5

Carcinoma of the gallbladder is a malignant epithelial neoplasm arising in

the gallbladder from biliary epithelium. The most common site is the fundus (60%)

followed by the body (30%) and neck (10%). Most tumours are flat, with extensive

overlap into different sections of the gallbladder.10

8
 Fig 8. The gall bladder is composed of a highly folded mucosa (lacking a muscularis mucosae),
an irregularly arranged muscularis externa without an intervening submucosa, and either an
adventitia binding the gall bladder to the liver or a serosa on its peritoneal surface. 40x.11

The signs and symptoms are nonspecific and indistinguishable from those

produced by gallstones. Right upper quadrant pain is common. More than 50% of

cases are diagnosed incidentally at a late stage. Ultrasound and CT are useful in a

small fraction of cases involving non-flat tumours.10

The most common risk factors for development of gallbladder carcinoma are

gallstones and chronic cholecystitis.Up to 95% of gallbladder carcinomas are

associated with gallstones. Patients with gallstones larger than 2–3 cm have the

greatest risk of developing cancer. The type of gallstone may also be important,

with cholesterol stones showing the greatest risk..12,6

Additional risk factors include smoking, high parity, elevated body mass

index, and chronic bacterial infection with Helicobacter pylori or Salmonella.

Ulcerative colitis is a well-described risk factor for primary sclerosing cholangitis

and all biliary malignancies. Patients with ulcerative colitis have a 10-fold risk of

developing gallbladder carcinoma. Anomalous pancreaticobiliary duct junction—a

congenital anomaly—occurs when the biliary and pancreatic ducts join more
9
 proximally than normal and is associated with an increase in all biliary tract cancers,

including gallbladder carcinoma.13,6

Inflammation appears to be the main event in gallbladder carcinogenesis,

including metabolic syndrome, in which the effects of growth factors, adipokines,

and cytokines are believed to contribute to the risk.14 It is believed that in these cases

the carcinogenetic sequence involves inflammation, atrophy, metaplasia, dysplasia,

and carcinoma, a process that may take decades. A distinct type of gallbladder injury

called hyalinizing cholecystitis (also known as incomplete porcelain gallbladder) has

also been identified with close association to GBC. It has been shown that selective

mucosal calcification rather than the diffuse intramural calcification detected

radiologically is the herald of the type of hyalinizing cholecystitis that has a

substantial cancer risk.10 Pancreatobiliary maljunction allows pancreatic enzymes to

escape into the gallbladder and leads to a distinctive type of mucosal hyperplasia,

followed by carcinogenesis that often undergoes a dysplasia–carcinoma sequence. In

this disorder, a chemical phenomenon, not necessarily inflammation, may be the

culprit. Some carcinomas appear to arise in adenomyomas, but it remains to be

determined whether these have a different etiopathogenesis or are dependent on the

duration of chronic inflammation.10,15,16

Like other neoplasms, GBC is a product of the accumulation of multiple

genetic alterations resulting from an interaction between a genetic predisposition and

exposure to an environmental risk factor. More than 50% of GBCs

harbour TP53 alterations. Other more common mutations include alterations

in CDKN2A or CDKN2B (19%), ARID1A (13%), PIK3CA (10%),and CTNNB1 (10).

Amplifications of ERBB2 (16%) have been reported. Microsatellite instability

and CDKN2A inactivation by promoter methylation have been reported in preinvasive

10
and invasive lesions. The dysplasia–carcinoma sequence appears to go through

different pathways, with paucity of mutations in TP53 and CDKN2A and a higher

frequency of mutations in CTNNB1 (encoding β-catenin). A higher KRAS mutation

rate in lesions related to the pancreatobiliary maljunction but not in flat precursor

lesions has been reported.10

Typical imaging features of localized disease include asymmetric gallbladder

wall thickening, polyps larger than 1.0 cm, and a solid mass replacing the gallbladder

lumen. Advanced tumors are often infiltrative and can be confusing at CT and MRI

owing to their large size. Determination of the origin of the lesion is paramount to

narrow the differential diagnosis but is often challenging. It is important to identify

gallbladder cancer and distinguish it from other benign and malignant hepatobiliary

processes. Since surgical resection is the only curative treatment option, radiologist

understanding and interpretation of pathways of nodal and infiltrative tumor spread

can direct surgery or preclude patients who may not benefit from surgery. While both

CT and MRI are effective, MRI provides superior soft-tissue characterization of the

gallbladder and biliary tree and is a useful imaging tool for diagnosis, staging, and

evaluation of treatment response.6

Macroscopic appearance, Most Gallbladder cancers (GBCs) this (70%) arise

in the fundus of the gallbladder. They are usually flat, firm, white, gritty, granular, and

poorly defined tumours that typically grow diffusely. It is often difficult to distinguish

carcinoma from chronic cholecystitis not only preoperatively and in the operating

room but also, as careful sampling studies from Chile elucidated, even with thorough

macroscopic examination, which misses as many as 30% and 70% of advanced (pT2)

and muscle-confined cases, respectively. GBCs arising from intracholecystic papillary

neoplasms by definition have an exophytic component that can fill the lumen of the

11
gallbladder. Mucinous tumours have a more gelatinous appearance, and sarcomatoid

and undifferentiated tumours might have a polypoid contour with fleshy appearance.10

Histopathological subtypes Gallbladder cancers (GBCs) are:

1. Biliary-type adenocarcinoma

Most ordinary GBCs belong to this group, which is also referred to as

pancreatobiliary-type, because it is very similar in both morphology and behaviour to

pancreatic ductal adenocarcinoma, being composed of widely separated tubular units

lined by cuboidal to columnar cells embedded in a variably cellular or collagenized

desmoplastic stroma. The cytoplasmic contents vary from case to case and between

areas of a given case, and can range from more mucin-containing to foamy (also

designated foamy gland adenocarcinoma), whereas some have more attenuated

cytoplasm with a microcystic glandular appearance. Some are exceedingly well

differentiated to an extent that they can be difficult to distinguish from benign lesions.

The vast majority of cases have the small tubular pattern, but some biliary

adenocarcinomas exhibiting the large glandular pattern can have substantial papillary

and cribriform areas. Poorly differentiated examples exhibit various patterns of

growth, from single cells, cords, and nests to a sheet-like arrangement, often showing

substantial pleomorphism and bizarre nuclei.10

Micropapillary carcinoma as described in the lower pancreatobiliary tract or

urothelium can also occur and raises concern for more aggressive dissemination

potential. Of importance, ordinary biliary adenocarcinomas can be accompanied by

any one of the other carcinoma types described below, but as long as the predominant

pattern is the ordinary biliary type then the case is classified as such.10

Some of the ordinary (biliary-type) adenocarcinomas display more

cytoplasmic mucin with the nuclei compressed at the periphery, creating a picture

12
reminiscent of gastric foveolar cells. Foamy gland adenocarcinomas have also been

documented under this group by some authors. These adenocarcinomas have not been

proven to be substantially different from ordinary biliary-type adenocarcinomas.10

2. Intestinal-type adenocarcinoma

Carcinomas with tubular configuration, more columnar cells, and elongated

pseudostratified nuclei, resembling colonic adenocarcinomas, have been designated

under the heading of “intestinal-type adenocarcinoma”, but these appear to be very

uncommon. In fact, if a carcinoma is displaying this morphology in the gallbladder,

careful analysis is warranted to rule out involvement by a colonic adenocarcinoma.

Distinctive features of colonic adenocarcinomas, including central necrosis, goblet

cell–like intestinal mucin, and cellular basophilia, are uncommon in the gallbladder.

An unusual subtype consisting of glands lined predominantly by goblet cells with

variable amounts of Paneth and neuroendocrine cells has been described in this

group.10

3. Mucinous adenocarcinoma

GBC shows some degree of stromal mucin deposition in approximately 7%

of all cases, and a third fulfil the conventional criteria of > 50% of the tumour

containing extracellular mucin. These are similar to those arising in other anatomical

sites, and some are mixed mucinous–signet-ring cell carcinomas. Pure colloid-type

mucinous carcinoma is exceedingly uncommon in the gallbladder. Mucinous

carcinomas are typically large and advanced at the time of diagnosis. They appear to

exhibit more-aggressive behaviour than ordinary GBC, and unlike gastrointestinal

mucinous carcinomas, they are microsatellite-stable.10

4. Clear cell carcinoma

Clear cell (hypernephroid) carcinoma is characterized by sheets of clear cells

13
in an alveolar arrangement and separated by sinusoid vessels. Invariably,

conventional patterns of ordinary adenocarcinoma growth are found somewhere in

the tumour. It is an exceedingly uncommon type of carcinoma in the biliary tract. In

fact, if it is a pure pattern, then the possibility of a metastatic clear cell renal

carcinoma should be considered foremost.10

5. Poorly cohesive carcinoma with or without signet-ring cells

These carcinomas are now defined as they are in the GI tract (in particular

the stomach). They are characterized by individual cell (poorly cohesive cell) and

cord-like patterns forming the diffuse infiltrative growth in which the cells dissect

through the tissue planes, leaving the underlying structures such as the musculature

intact, resulting in the linitis plastica pattern grossly. Plasmacytoid cells (as described

in the urothelium) and signet-ring cells characterized by abundant mucin pushing the

nucleus to the periphery and thus creating the signet-ring cell cytology occur in some

cases but are not a requirement. As many as 8% of conventional biliary-type

carcinomas in the gallbladder exhibit a focal component of this pattern. Tumours

composed predominantly of this pattern occur rarely. They are more frequent in

women and clinically show a behaviour more aggressive than that of ordinary

GBC.17

6. Adenosquamous carcinoma

Focal squamous differentiation is found in approximately 5% of gallbladder

carcinomas. If squamous elements constitute a substantial part of the tumour (>

25%), the neoplasm is best classified as an adenosquamous carcinoma. Glandular

and squamous components of the tumours have corresponding immunophenotypes.

Additional sampling often reveals the adenocarcinoma component in a seemingly

pure squamous cell carcinoma.10

14
 7. Squamous cell carcinoma

Bona fide examples of pure squamous cell carcinoma with squamous cell

carcinoma in situ as well are exceedingly uncommon. They often show substantial

keratinization. Like in the pancreas and breast, squamous differentiation appears to

confer an even more aggressive behaviour on GBCs, with more-advanced

presentation and worse prognosis.10

8. Other differentiation patterns

Some carcinomas have an undifferentiated (non-glandular, nondescript)

morphology. Some form patchy solid clusters of carcinoma cells without evidence

of glandular differentiation. Various subtypes are recognized. Some form stroma-

poor sheets of cells akin to medullary carcinomas of the GI tract, some also

exhibiting the cytology of lymphoepithelioma-like carcinomas of the upper

aerodigestive tract, although not yet with proven association with EBV.10

Bona fide primary hepatoid carcinomas (as proven with the presence of

high-grade dysplasia and/or a mixed ordinary adenocarcinoma component in the

gallbladder, without pre-existing hepatocellular carcinoma) also occur and can

show Hep Par-1 positivity, but they must be distinguished from hepatocellular

carcinoma invading the gallbladder.10

Sarcomatoid carcinoma with spindle cell morphology can also occur in the

gallbladder. Sarcomatoid components may be subtle and fibroblast-like, but they

are more commonly pleomorphic (including giant cells) or may show evidence of

heterologous differentiation (i.e. skeletal muscle, bone, and cartilage).10

The prognosis carcinoma of the gallbladder if perimuscular invasion (T2)

has been ruled out by total sampling of the gallbladder, muscle-confined (EGBC)

cases may be curable in most instances. Some T2 carcinomas that are very

15
superficial/limited may also be successfully treated, but deeply invasive tumours

are aggressive, with a 5-year overall survival rate ranging from 45% to 70%. These

survival differences appear to be unrelated to pathological criteria and sampling,

and reflect population or diagnosis/management differences.10

Fig 9. Carcinoma of the gallbladder. Well-differentiated adenocarcinoma infiltrating the gallbladder

muscle layer, biliary type.10

Fig 10. Carcinoma of the gallbladder. Adenocarcinoma of the gallbladder, intestinal type,
resembling colonic adenocarcinoma.10

16
Fig 11. Clear cell carcinoma. Clear cell carcinoma change characterized by optically clear cytoplasm
and distinct cell borders, mimicking renal cell carcinoma.10

Fig 12. Carcinoma of the gallbladder. Colloid carcinoma with > 90% of the tumour composed of
well-defined stromal mucin nodules with scant carcinoma cells encased in the mucin.10

17
 Table 1. TNM Staging of tumour of the gallbladder.10

T Primary Tumour

Tx Primary cannot be assessed

T0 No evidence of primary tumour

Tis Carcinoma in situ

T1 Tumour invades lamina propia & muscle layer
a. Tumour invades lamina propia
b. Tumour invades muscle layer
T2 Tumour invades perimuscular connective tissu; no extension
beyond serosa or into liver
a. Tumour invades perimuscular connective tissue on the
peritoneal side without serosal involvement
b. Tumour invades perimuscular connective tissue on the
hepatic side (without hepatic involvement) or both
hepatic and peritoneal sides
T3 Tumour perforates the serosa (visceral peritonium) and/or
directli invades the liver and/ or one other adjacent organ or
structure, such as stomach, duodenum, colon or pancreas,
omentum or extrahepatic bile ducts
T4 Tumour invades main portal vein or hepatic artery or invades
two or more extrahepatic organs or structures
N- Regional lymph nodes

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis
N1 Metastasis to one to there regional lymph nodes
N2 Metastasis to four or more regional lymph nodes
M-Metastasis
M0 No distant metastasis
M1 Distant metastasis

18
 Stage Gallbladder

Stage 0 Tis N0 M0

Stage 1A T1a N0 M0

Stage 1B T1b N0 M0

Stage 2A T2a N0 M0

Stage 2B T2b N0 M0

Stage 3A T3 N0 M0

Stage 3B T1. T2. T3 N1 M0

Stage 4A T4 N0.N1 M0

Any T N2 M1

CONCLUSION

Carcinoma of the gallbladder is a malignant epithelial neoplasm arising in the

gallbladder from biliary epithelium. The most common site is the fundus (60%) followed

by the body (30%) and neck (10%). Most tumours are flat, with extensive overlap into

different sections of the gallbladder. A 52 year old men, came to a hospital with

complaints upper right abdominal pain. Based on clinical and microscopic

examination this case was diagnosed as adenocarcinoma NOS with ICD-O codes

: 8140/3, topography morphology: C23.9.

19
 DAFTAR PUSTAKA

1. Rawla, P.; Sunkara, T.; Thandra, K.C.; Barsouk, A. Epidemiology of gallbladder

cancer. Clin. Exp. Hepatol. 2019, 5, 93–102.
2. Dyba, T.; Randi, G.; Bray, F.; Martos, C.; Giusti, F.; Nicholson, N.,et al. The
European cancer burden in 2020: Incidence and mortality estimates for 40 coutries
and 25 major cancers. Eur. J. Cancer 2021, 157, 308–347.
3. Vega, E.A.; Newhook, T.E.; Vauthey, J.-N. ASO Author Reflections: Gallbladder
Cancer Research, “One for All and All for One” Strategy to Improve
Research. Ann. Surg. Oncol. 2021, 28, 2683–2684.
4. Jang, J.; Yoo, D.-S.; Chun, B.C. Spatial epidemiologic analysis of the liver cancer
and gallbladder cancer incidence and its determinants in South Korea. BMC
Public Health 2021, 21, 2090.
5. Sharma, A.; Sharma, K.; Gupta, A.; Yadav, A.; Kumar, A. Gallbladder cancer
epidemiology, pathogenesis and molecular genetics: Recent update. World J.
Gastroenterol. 2017, 23, 3978–3998.
6. Camila LV, MD Michael J, MD Pardeep K. M, MD Courtney C. Moreno, MD
Frank H, et.al. From the Department of Radiology, Northwestern Memorial
Hospital, Northwestern University Feinberg School of Medicine, 676 N St Clair
St, Suite 800, Chicago, IL 60611 (C.L.V., M.J.M., F.H.M.); Department of
Radiology, Medical College of Georgia, Augusta, Ga (P.K.M.); and Department
of Radiology and Imaging Sciences, Emory University, Atlanta, Ga (C.C.M.).
RadioGraphics 2021; 41:78–95 https://doi.org/10.1148/rg.2021200087

7. Kalbi, D.P.; Bapatla, A.; Chaudhary, A.J.; Bashar, S.; Iqbal, S. Surveillance of
Gallbladder Polyps: A Literature Review. Cureus 2021, 13, e16113.
8. McCain, R.S.; Diamond, A.; Jones, C.; Coleman, H.G. Current practices and
future prospects for the management of gallbladder polyps: A topical
review. World J. Gastroenterol. 2018, 24, 2844–2852.
9. Albores-Saavedra, J.; Henson, D.E.; Klimstra, D.S. Tumors of the Gallbladder,
Extrahepatic Bile Ducts, and Vaterian System; American Registry of Pathology:
Washington, DC, USA, 2015.
10. Basturk O, Aishima S, Esposito I. Biliary Intraepithelial Neoplasia. In: WHO
Classification of Tumours Editorial Board. Digestive System Tumours. Lyon:

20
 IARC; 2019. P273-275.

11. Gallbladder – Normal Histology. https://digitalhistology.org/organs

systems/digestive/major-glands/gall-bladder/gall-bladder-1/

12. Sachs TE, Akintorin O, Tseng J. How should gallbladder cancer be managed. Adv
Surg 2018;52(1):89–100.
13. Jaruvongvanich V, Yang JD, Peeraphatdit T, Roberts LR. The incidence rates
and survival of gallbladder cancer in the USA. Eur J Cancer Prev 2019;28(1):1–
14. Feakins RM. Obesity and metabolic syndrome: pathological effects on the
gastrointestinal tract. Histopathology. 2016 Apr;68(5):630-40. doi:
10.1111/his.12907. Epub 2016 Jan 19. PMID: 26599607.
15. Muraki T, Memis B, Reid MD, Uehara T, Ito T, Hasebe O, Okaniwa S,et al.
Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the
Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction)
Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to
Carcinoma. Am J Surg Pathol. 2017 Sep;41(9):1167-1177. doi:
10.1097/PAS.0000000000000882. PMID: 28622182; PMCID: PMC8722026.
16. Morikawa T, Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Saisaka Y, et. Al.
Adenomyomatosis Concomitant with Primary Gallbladder Carcinoma. Acta Med
Okayama. 2017 Apr;71(2):113-118. doi: 10.18926/AMO/54979. PMID:
28420892.

17. Tuncel D, Roa JC, Araya JC, Bellolio E, Villaseca M, Tapia O, et. Al. Poorly
cohesive cell (diffuse-infiltrative/signet ring cell) carcinomas of the gallbladder:
clinicopathological analysis of 24 cases identified in 628 gallbladder carcinomas.
Hum Pathol. 2017 Feb;60:24-31. doi: 10.1016/j.humpath.2016.09.008. Epub
2016 Sep 22. PMID: 27666767

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