Systematic Reviews Open Access
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Dec 27, 2020; 12(12): 534-548
Published online Dec 27, 2020. doi: 10.4240/wjgs.v12.i12.534
Ectopic liver tissue (choristoma) on the gallbladder: A comprehensive literature review
Sami Akbulut, Felat Ciftci, Cemalettin Koc, Adem Tuncer, Emrah Sahin, Sezai Yilmaz, Department of Liver Transplant Institute, Inonu University, Malatya 44280, Turkey
Khaled Demyati, Department of Surgery, An-Najah National University, Nablus 11941, Palestine
Nese Karadag, Department of Pathology, Inonu University Faculty of Medicine, Malatya 44280, Turkey
ORCID number: Sami Akbulut (0000-0002-6864-7711); Khaled Demyati (0000-0002-9591-2664); Felat Ciftci (0000-0002-8958-7121); Cemalettin Koc (0000-0002-5676-6772); Adem Tuncer (0000-0001-5381-513X); Emrah Sahin (0000-0001-5267-9068); Nese Karadag (0000-0003-0886-8122); Sezai Yilmaz (0000-0002-8044-0297).
Author contributions: Akbulut S, Koc C and Yilmaz S designed the report; Tuncer A, Ciftci F, Koc C, Sahin E and Akbulut S performed the literature review; Akbulut S and Demyati K organized the report and wrote the paper; Karadag N provided the histopathological information; all authors reviewed the final version.
Conflict-of-interest statement: There is no conflict of interest associated with the senior author or other coauthors who contributed to this manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sami Akbulut, MD, Professor, Department of Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, Malatya 44280, Turkey. akbulutsami@gmail.com
Received: September 26, 2020
Peer-review started: September 26, 2020
First decision: October 21, 2020
Revised: November 12, 2020
Accepted: December 2, 2020
Article in press: December 2, 2020
Published online: December 27, 2020

Abstract
BACKGROUND

Liver tissue situated outside the liver with a hepatic connection is usually called an accessory liver, and that without a connection to the mother liver, is called ectopic liver tissue.

AIM

To identify studies in the literature on ectopic liver tissue located on the gallbladder surface or mesentery.

METHODS

We present two patients and review published articles on ectopic liver tissue located on the gallbladder surface accessed via PubMed, MEDLINE, Google Scholar, and Google databases. Keywords used included accessory liver lobe, aberrant liver tissue, ectopic liver tissue, ectopic liver nodule, heterotopic liver tissue, hepatic choristoma, heterotopic liver tissue on the gallbladder, and ectopic liver tissue on the gallbladder. The search included articles published before June 2020 with no language restriction. Letters to the editor, case reports, review articles, original articles, and meeting presentations were included in the search. Articles or abstracts containing adequate information on age, sex, history of liver disease, preliminary diagnosis, radiologic tools, lesion size, surgical indication, surgical procedure, and histopathological features of ectopic liver tissue were included in the study.

RESULTS

A total of 72 articles involving 91 cases of ectopic liver tissue located on the gallbladder surface or mesentery were analyzed. Of these 91 patients, 62 were female and 25 were male (no gender available for 4 patients), and the age range was 5 d to 91 years. Forty-nine patients underwent surgery for chronic cholecystitis or cholelithiasis, and 14 patients underwent surgery for acute cholecystitis. The remaining 28 patients underwent laparotomy for other reasons. Cholecystectomy was laparoscopic in 69 patients and open in 11 patients. The remaining 19 patients underwent various other surgical procedures such as autopsy, liver transplantation, living donor hepatectomy, Whipple procedure, and liver segment V resection. Histopathologically, hepatocellular carcinoma was detected in the ectopic liver tissue of one patient.

CONCLUSION

Ectopic liver tissue is a rare developmental anomaly which is usually detected incidentally. Although most studies suggest that ectopic liver located outside the gallbladder has a high risk of hepatocellular carcinoma, this is not reflected in statistical analysis.

Key Words: Liver, Gallbladder, Ectopic liver tissue, Hepatic choristoma, Histopathological features, Hepatocellular carcinoma

Core Tip: Ectopic liver tissue is a rare developmental anomaly usually detected incidentally. While it is often asymptomatic, there is a risk of malignant transformation and other complications such as bleeding and torsion. In this review, we present two cases of ectopic liver tissue located on the gallbladder surface and review published studies on ectopic liver tissue located on the gallbladder surface accessed via the PubMed, MEDLINE, Google Scholar, and Google databases. Although most studies suggest that ectopic liver located outside the gallbladder has a higher risk of hepatocellular carcinoma, this is not reflected in the statistical analysis.
INTRODUCTION

Ectopic liver tissue is a rare developmental anomaly in which the liver tissue is situated outside the liver. It is usually asymptomatic and is discovered incidentally during surgery or autopsy, but there are potential complications. Torsion, malignant transformation, compression of adjacent organs, and intra-peritoneal bleeding are among the possible complications[1-72].

Liver tissue situated outside the liver with a hepatic connection is usually called an accessory liver, and that without a connection to the main liver, is called ectopic liver tissue. Accessory liver and ectopic liver tissues were first described by Morgagni in 1767 and by Corsy in 1922, respectively[1,20,36,72]. Subsequent reports showed that the accessory liver lobe most commonly occurs in the gallbladder wall, under the surface of the liver, at the gastrohepatic ligament, umbilical cord, adrenal glands, pancreas, pylorus, diaphragm, and the splenic capsule if a portion of the pars hepatica is displaced[28,31,34,44,36]. The histological architecture of the ectopic tissue resembles normal liver, although it does not have a complete functional architecture, is metabolically handicapped, and is more prone to carcinogenesis[2,6,36,40,62,72]. In this article, we report two cases of ectopic liver tissue and review the literature for articles published on ectopic liver tissue on the gallbladder surface or gallbladder mesentery[1-72]. The clinical and pathological characteristics are described in addition to an analysis of the possible clinical implications including malignant transformation.

MATERIALS AND METHODS

The primary aim of this study was to review the articles published in the literature on ectopic liver tissue on the gallbladder surface or gallbladder mesentery. To achieve this aim, a literature search was conducted on PubMed, MEDLINE, Google Scholar, and Google databases using the following keywords: Accessory liver lobe, aberrant liver tissue, ectopic liver tissue, ectopic liver nodule, heterotopic liver tissue, hepatic choristoma, liver, gallbladder, heterotopic liver tissue on the gallbladder, ectopic liver tissue on the gallbladder, accessory liver lobe on the gallbladder, accessory liver tissue on the gallbladder alone or in different combinations. Language restrictions were not applied in this literature review. All documents published on ectopic liver tissue related to the gallbladder before June 2020 were reviewed. Patients with ectopic liver tissue found in the gallbladder lumen incidentally were excluded from the study. As a result, articles without an accessible full-text version, those without adequate information in the abstract, and those that did not include comprehensive information compared to other studies were excluded. The following information was collected: Publication year, country, type of article available (full-text, abstract), age, sex, clinical presentation, diagnostic modalities, indication for surgery, surgical approach, postoperative complications, and histopathologic features of specimens. The details of the literature search are provided in Table 1. The secondary aim of this study was to present two cases of ectopic liver tissue attached to the gallbladder wall that was discovered during living donor hepatectomy and recipient hepatectomy.

Table 1 Summary of the demographic and clinicopathological characteristics of 91 patients published in the literature between 1925 and 2020.
Ref.
Year
Country
Language
Age
Sex
History of liver disease
Preliminary diagnosis
Radiologic tools
Kachi et al[1]2020LebanonEnglish44FNoCCUS
62FNoCCNA
Avdaj et al[2]2020KosovoEnglish47FNoCCUS
Baral et al[3]2019United StatesEnglish67FNoCCUS
Yuksel et al[4]2019TurkeyEnglish34FNACCUS
Mannan et al[5]2019S. ArabiaEnglish38FNAACUS
Isa et al[6]2019BahrainEnglish42FNoCCUS
Pandit et al[7]2019NepalEnglish30FNABiliary pancreatitis US + MRCP
Granek et al[8]2019AustraliaEnglish36MNAACUS
Lodha et al[9]2018IndiaEnglish50MNAKidney tumorCT
Topcu et al[10]2018TurkeyEnglish64FNAACUS
70FNAIcterusUS + CT + MR
Burke et al[11]2018IrelandEnglish30FNACCUS
Greenberg et al[12]2018United StatesEnglish52FFLDAPUS + CT
Termos et al[13]2017KuwaitEnglish73FNAGBCUS + CT
Weber-Alvarez et al[14]2017MexicoEnglish37FNAACUS
Galimov et al[15]2017RussiaRussian70MNAACUS
Handra-Luca et al[16]2016FranceEnglish68FNACCUS
56FNACCUS
Mani et al[17]2016United StatesEnglish56MFLDACCT
Ito et al[18]2016JapanEnglish59FNACCMR + CT
Leena et al[19]2016IndiaEnglish25MNACadaverAutopsy
Karaca et al[20]2016TurkeyEnglish43FNACCUS
Jaboury et al[21]2016AustraliaEnglish22FNACCNA
Yahya et al[22]2016LibyaEnglish35FNACCUS
45FNACCUS
45FNACCNA
20FNAPenetrating injuryNA
Aslan et al[23]2016TurkeyEnglish49FNACCUS
Longjam et al[24]2016IndiaEnglish42FNACCUS
Kostov et al[25]2016BulgariaEnglish49MRCLMRCLMNA
Bal et al[26]2015TurkeyEnglish51FNACCUS
Smyth et al[27]2015AustraliaEnglish77FNACCUS
Abhilash et al[28]2015IndiaEnglish45FNAACUS
Hussein et al[29]2015LebanonEnglish49FNAACCT
Yankol et al[30]2015TurkeyEnglish30MNoLiving donorUS + CT + MRCP
Arslan et al[31]2014TurkeyEnglish59FNACCUS
Pulle et al[32]2014IndiaEnglish43FNACCUS
Terakawa et al[33]2014JapanJapanese33FNACCUS + MRCP
Sirasanagandla et al[34]2013IndiaEnglish62MNACadaverNA
Hassan et al[35]2013IndiaEnglish32FNACCUS
Martinez et al[36]2013BrazilEnglish37FNAACUS
Ozturk et al[37]2013TurkeyTurkish35FNoCCUS
Yajima et al[38]2013JapanJapanese73FNACCUS + CT
Khan et al[39]2013IndiaEnglish32FNACCNA
Karaman et al[40]2012TurkeyEnglish63MNACCUS
Patel et al[41]2012United KingdomEnglish21FNACCUS
Sozen et al[42]2012TurkeyTurkish40FNACCUS
Catani et al[43]2011ItalyEnglish72FNAACUS
83FNoCCUS
Dettmer et al[44]2011SwitzerlandEnglish91FNAACCT
Nagar et al[45]2011United StatesEnglish25FNAAP + Cystic massUS + CT + MRCP
Ates et al[46]2010TurkeyTurkish64FNAACNA
49MNACCUS
Triantafyllidis et al[47]2009GreeceEnglish56FNACCUS
Guzman et al[48]2009MexicoSpanish36MNACCUS
Kyeong et al[49]2008S. KoreaEnglish66FNACCCT
Koh et al[50]2007AustraliaEnglish60FNAACNA
Malhas et al[51]2007United KingdomEnglish42MFLDCCUS
39FNACCUS
Soto et al[52]2007United StatesEnglish32FNACCUS
Beltran et al[53]2007ChileEnglish47MNACCUS
33FNACCUS
27MNAGastric cancer US + CT
35MNAPancreatic pseudocyst US + CT
Wang et al[54]2006ChinaChinese38MNAGallbladder polypsUS
Ikeda et al[55]2006JapanEnglish70MNoHCC + CirrUS + CT
Ngowe et al[56]2006CameroonFrench46FNACCUS
Lundy et al[57]2005United StatesEnglish38FFLDLiver tumorUS + CT
Leone et al[58]2004ItalyEnglish54FNOGBCUS + CT
Griniatsos et al[59]2002United KingdomEnglish39FNACCUS
49MNACCUS
Acar et al[60]2002TurkeyEnglish55FNACCUS
Sakarya et al[61]2002TurkeyEnglishNANANANANA
Arakawa et al[62]1999JapanEnglish48MALDALDAutopsy
Hamdani et al[63]1994United StatesEnglish49MCirrPSCUS + CT
Boyle et al[64]1992United StatesEnglish44FNoACUS
Tejada et al[65]1989United StatesEnglish43MNACC + HSUS
Watanabe et al[66]1989JapanEnglish37MCLLCLLCT
54MCirrALDLaparoscopy
64FCirrCirrCT
71FCirrCirrLaparoscopy
Fellbaum et al[67]1987AustriaGerman34FNACCNA
Natori et al[68]1986JapanEnglish56FNACCCT
Ashby et al[69]1969United KingdomEnglish42MNADuodenal ulcerNA
BASSIS et al[70]1956United StatesEnglishNANANACCNA
NANANACCNA
NANANACCNA
5dMNACadaverNo
Thorsness et al[71]1941United StatesEnglish63FNACadaverNo
Cullen et al[72]1925United StatesEnglish33FNoJaundiceNA
CC: Chronic cholecystitis ± cholelithiasis; US: Ultrasound; NA: Non-available; AC: Acute cholecystitis; MRCP: Magnetic resonance cholangiopan-creatography; CT: Computed tomography; MR: Magnetic resonance; FLD: Fatty liver disease; GBC: Gallbladder cancer; RCLM: Rectum cancer liver metastasis; ALD: Alcoholic liver disease; PSC: Primary sclerosing cholangitis; Cirr: Cirrhosis; HS: Hereditary spherocytosis; CLL: Cystic liver lesion; AP: Abdominal pain.
RESULTS
Review of the literature

Using the PubMed, MEDLINE, Google Scholar, and Google databases, 72 articles involving 91 patients published between January 1925 and August 2020 were compatible with the above-mentioned criteria. The four countries with the highest numbers of published articles were Turkey (n = 13), the United States (n = 12), India (n = 8), and Japan (n = 7). Sixty-two articles were written in English, three in Turkish, two in Japanese, one in French, one in German, one in Chinese, one in Russian, and one in Spanish. The full text was obtained for 69 of the 72 articles, whereas only abstracts were available for three articles. Of the 91 patients, 62 were female and 25 male; no gender data were available for the remaining four patients. The age of these 87 patients ranged from five days to 91 years; this information was unavailable for the remaining four patients.

Eleven patients had a history of various liver diseases, while 12 patients had no liver disease. No data could be obtained on whether the remaining 68 patients had any liver disease. Forty-nine patients underwent surgery for chronic cholecystitis and/or cholelithiasis, while 14 patients underwent surgery for a presumed diagnosis of acute cholecystitis. The remaining 28 patients underwent laparotomy for unrelated reasons. Sixty-one patients underwent laparoscopic cholecystectomy and 11 underwent open cholecystectomy. The remaining 19 patients underwent cholecystectomy and various surgical procedures such as autopsy, liver transplantation, living donor hepatectomy, Whipple procedure, and liver segment V resection. Demographic, clinical, and histopathological characteristics of the 91 patients with ectopic liver tissue are summarized in Tables 1 and 2.

Table 2 Summary of the surgical and histopathological characteristics of 91 patients published in the literature between 1925 and 2020.
Ref.
Lesion sizes (mm)
Surgical indication
Surgical procedure
Histopathological findings of ELT
Histopathological findings of GB
Kachi et al[1], 202010CCLCELTNA
5CCLCELTNA
Avdaj et al[2], 2020NACCLCELTNA
Baral et al[3], 201930CCLCELTNA
Yuksel et al[4], 201917CCLCELTCC
Mannan et al[5], 20195ACLCELTNA
Isa et al[6], 2019NACCLCELTNA
Pandit et al[7], 201935CCLCELTNA
Granek et al[8], 201919ACLCELTNA
Lodha et al[9], 201820Kidney tumorLap nephrectomyELT (no excised)NA
Topcu et al[10], 201815CCOCELTNA
80Pancreatic tumorWhipple procedureELTNA
Burke et al[11], 2018NACCLCELTNA
Greenberg et al[12], 201830CCLCELTNA
Termos et al[13], 201730Diag lapLCELTNA
Weber-Alvarez et al[14], 201710ACLCELTAC + CC
Galimov et al[15], 20176ACLCELTPhlegmonous cholecystitis
Handra-Luca et al[16], 20165CCLCELTCC
11CCLCELTCC
Mani et al[17], 2016NACCLCELTNA
Ito et al[18], 201615CCLCELTNA
Leena et al[19], 201615AutopsyAutopsyELTNA
Karaca et al[20], 201615CCLCELTNA
Jaboury et al[21], 2016NACCLCELTNA
Yahya et al[22 ], 201660CCLCELTNA
NACCLCELTNA
NACCLCELTNA
NAPenetrating injuryDiag lapELTNA
Aslan et al[23], 20168CCLCELTNA
Longjam et al[24], 201615CCLCELTCC
Kostov et al[25], 201635RCLMOCELTHydatid cyst on gallbladder wall
Bal et al[26], 201520CCLCELTNA
Smyth et al[27], 201520CCLCELTCC
Abhilash et al[28], 201510ACLCELTCC
Hussein et al[29], 2015NAACLCELTNA
Yankol et al[30], 201515Donor hepatectomyLDHELTAccessory gallbladder tissue
Arslan et al[31], 201420CCLCELTNA
Pulle et al[32], 201420CCLCELTCC
Terakawa et al[33], 201412CCLCELTNA
Sirasanagandla et al[34], 201320AutopsyAutopsyELTNA
Hassan et al[35], 201310CCLCELTCC
Martinez et al[36], 201330CCLCELTChronic inflammation
Ozturk et al[37], 201320CCLCELTNA
Yajima et al[38], 20136CCLCELTNA
Khan et al[39], 2013NACCLCELT (Fatty change)CC
Karaman et al[40], 201211CCLCELTNA
Patel et al[41], 201226CCLCELTNA
Sozen et al[42], 20127CCLCELTNA
Catani et al[43], 201115ACLCELTNA
14CCLCELTNA
Dettmer et al[44], 201115ACLCELTAcute cholecystitis
Nagar et al[45], 201145AP + Cystic massLCELTCC
Ates et al[46], 20105ACLCELTNA
6CCLCELTNA
Triantafyllidis et al[47], 200915CCLCELTCC
Guzman et al[48], 200930CCLCELTNA
Kyeong et al[49], 200810CCLCELTCC
Koh et al[50], 200715ACLCELTNA
Malhas et al[51], 2007NACCLCELTNA
NACCLCELTNA
Soto et al[52], 20078CCLCELTNA
Beltran et al[53], 200712CCLCELTCC
17CCLCELTNA
7Gastric cancer OC + GastrectomyELTNA
18Pancreatic pseudocyst OC + GastrectomyELTNA
Wang et al[54], 200611Gallbladder polypsLCELTCC + Polyps
Ikeda et al[55], 2006NAHCCOC + Segment V ResectionNASHNA
Ngowe et al[56], 200630CCLCELTCC
Lundy et al[57], 200530Diag lapLCELTNA
Leone et al[58], 200490GBCOCELT + HCCNA
Griniatsos et al[59], 200210CCLCELTNA
15CCLCELTNA
Acar et al[60], 200214CCOCELTPapillary epithelial hyperplasia
Sakarya et al[61], 2002NANALCNANA
Arakawa et al[62], 199915AutopsyAutopsyELTNA
Hamdani et al[63], 199430PSCLTELTNA
Boyle et al[64], 199220ACOCELTCC
Tejada et al[65], 198911CCOC + SplenectomyELTCC
Watanabe et al[66], 19895Cystic lesion of the liverDiag lapBiliary hamartomaNA
8CirrDiag lapNANA
10CirrDiag lapNANA
6CirrDiag lapNANA
Fellbaum et al[67], 1987NANANANANA
Natori et al[68], 198612CCOC + ExcisionELTChronic inflammation
Ashby et al[69], 196910Duodenal ulcerOC + ExcisionELTNA
BASSIS et al[70], 195615CCOCELTCC
10CCOCELTCC
6CCOCELTCC
8AutopsyAutopsyELTNA
Thorsness et al[71], 19415AutopsyAutopsyELTNA
Cullen et al[72], 192512JaundiceExcisionNANA
NA: Non-available; LC: Laparoscopic cholecystectomy; AC: Acute cholecystitis; CC: Chronic cholecystitis ± cholelithiasis; RCLM: Rectum cancer liver metastasis; PSC: Primary sclerosing cholangitis; GBC: Gallbladder cancer; LDH: Lactate dehydrogenase; OC: Open cholecystectomy; Diag lap: Diagnostic laparoscopy; ELT: Ectopic liver tissue; HCC: Hepatocellular cancer.
Case presentations

Case 1: A 25-year-old woman [body mass index (BMI): 27 kg/m2, A Rh (+), graft volume: 600 cc, remnant liver: 29%] was admitted to our liver transplant institute to donate a part of her liver to her 33-year-old sister with cryptogenic liver cirrhosis. Radiological and biochemical examinations were completed using the preoperative donor evaluation algorithm available in our liver transplant institute. The donor candidate underwent laparotomy using a modified Makuuchi incision (reversed L-shaped incision). The exploration showed ectopic liver tissue approximately 15 mm × 5 mm in size, located in the gallbladder corpus, and had no association with the liver (Figure 1). Cholecystectomy was performed to include the ectopic liver tissue, and cholangiography was carried out via the cystic duct, and the biliary tract anatomy was found to be normal (Choi Type I). Right lobe donor hepatectomy was performed as previously described in our transplant institute. The donor was discharged without any postoperative complications. Macroscopically, the gallbladder specimen was 70 mm in length, 50 mm in diameter, and 3 mm in wall thickness. Histopathologically, the tissue (15 mm × 3 mm × 2 mm) located in the gallbladder corpus was ectopic liver tissue (Figure 2A and B).

Figure 1
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Figure 1 Intraoperative view of the ectopic liver tissue located in the gallbladder.
Figure 2
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Figure 2 Encapsulated liver tissue with normal histological features . A: HE × 1; B: HE × 2.5.

Case 2: A 45-year-old female patient with cryptogenic liver cirrhosis [BMI: 37.2 kg/m2, A Rh (-), MELD-Na: 16, Child: 10/C] presented to our liver transplant institute for live-donor liver transplantation. Both the liver recipient and the 40-year-old male [BMI: 25.5 kg/m2, A Rh (+), graft volume: 940 cc, remnant liver: 31%] living liver donor candidate were evaluated according to an algorithm consisting of radiological and biochemical analyses. Laparotomy was performed using a reversed L-shaped incision. During exploration, it was revealed that the liver had a macronodular appearance and a relatively small size. Ectopic liver tissue associated with the gallbladder mesentery was seen on the corpus of the gallbladder without an association with the liver. The ectopic liver tissue showed a cirrhotic appearance similar to the main liver tissue (Figure 3A and B). The gallbladder was removed en-bloc with the liver without recipient cholecystectomy as described previously (recipient hepatectomy). The recipient was discharged on postoperative day 15 without complications. The ectopic liver tissue, located in the gallbladder was also seen in the retrospective examinations of computed tomography sections (Figure 4).

Figure 3
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Figure 3 Intraoperative view of the ectopic liver tissue located in the gallbladder mesentery along with the main cirrhotic liver. A and B: The ectopic liver tissue was showed a cirrhotic appearance similar to the main liver tissue.
Figure 4
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Figure 4 Axial contrast-enhanced multidetector computed tomography section shows an ectopic liver tissue-like nodular lesion associated with the gallbladder.
DISCUSSION

Ectopic liver tissue is a rare developmental anomaly in which the liver tissue is situated outside the liver[9,19,28,60]. Four main types are described in the literature: Ectopic liver, which is not connected to the mother liver, and is usually attached to the gallbladder or intra-abdominal ligaments; microscopic ectopic liver found in the gallbladder wall; a large accessory liver lobe attached to the mother liver by a stalk; and a small accessory liver lobe, 10-30 g, attached to the mother liver[73]. However, this classification may not apply to all cases[60].

The real incidence of ectopic liver tissue attached to the gallbladder wall is difficult to assess; most cases are asymptomatic and are diagnosed at laparotomy, laparoscopy, or during an autopsy[1,2,14]. However, the incidence of ectopic liver tissue has been reported to range from 0.24% to 0.47%[2,31]. A review of 5500 autopsies showed that only 0.05% had ectopic liver tissue in which only three cases were attached to the gallbladder wall[74]. A review of 1060 laparoscopic procedures found ectopic liver tissue attached to the gallbladder wall in three patients (0.28%)[10]. To date, we detected only two (0.04%) patients with ectopic liver tissue among 4500 patients who underwent living donor hepatectomy or recipient hepatectomy

Different theories have been proposed to explain the development of an ectopic liver at various sites: Development of an accessory lobe of the liver with atrophy or regression of the original connection to the main liver; migration or displacement of a portion of the pars hepatica to other sites, entrapment of a nest of cells in the region of the foregut following closure of the diaphragm or umbilical ring and trapping of hepatocyte-destined mesenchyma in several areas thus budding hepatic tissue before the closure of the pleuroperitoneal canal[23,28]. Ectopic and accessory liver may occur at different sites, including sites close to the liver, such as the gallbladder and hepatic ligaments or sites far from the liver, for example, omentum, retroperitoneum, and thorax, with the most common location on the gallbladder[66,75,76].

Ectopic liver tissue varies considerably in size[60,62]. Based on 72 reports reviewed in this study, the average size of the ectopic liver tissue was found to be 17.8 mm. In the literature, the reported size of ectopic livers (without hepatocellular carcinoma) ranges from a few millimeters to several centimeters[24,44,58].

No detailed reports on the vascular supply of ectopic liver tissue were given in most of the papers reviewed. In general, three different vascular supply patterns have been described for gallbladder-associated ectopic liver tissue: An artery arising from the cystic artery[50], a vascular pedicle arising from the liver parenchyma substance[26], and vascular structures embedded in a mesentery lying from the hepatic site to ectopic liver tissue[43]. The identification of vascular supply requires surgery to avoid bleeding during the main surgery[3,4,26]. Extensive traction of the gallbladder should be avoided in cases with direct vascular supply from the liver substance. Biliary drainage was not described in detail or was not evident intraoperatively in most reports. In general, accessory liver lobes are classified into three types based on biliary drainage: In type I, the duct of the accessory liver lobe drains into an intrahepatic bile duct of the native liver; in Type II, it drains into an extrahepatic bile duct of the native liver, and if both the accessory lobe and the main liver have a common capsule and the bile duct of the accessory lobe drains into an extrahepatic duct, it is considered Type III[34,77].

Ectopic liver might be associated with other anomalies such as biliary atresia, agenesis of the caudate lobe, omphalocele, bile duct cyst, cardiac, and conotruncal anomalies; however, these abnormalities were not reported when the heterotopic tissue was attached to the surface of the gallbladder[28,59].

Ectopic liver tissue and accessory liver lobes are often asymptomatic, and detection of ectopic liver tissue before surgical intervention or autopsy imaging studies is rare[8,11,20,34]. However, ectopic livers on rare occasions have been reported to cause recurrent abdominal pain due to torsion[78-80], intraperitoneal bleeding[81,82], hemorrhagic necrosis[83], compression of adjacent organs[84], as well as obstruction of the esophagus[85], portal vein[86], and neonatal gastric outlet[87].

The histological architecture of the ectopic tissue resembles normal liver, with regular lobules, central veins, and normal portal areas in most cases[28,47,59]. Unusual architecture of hepatic tissue with absence of the classical hexagonal lobule pattern has been equally described[34]. Ectopic liver like the main liver tissue can undergo fatty changes, hemosiderosis, cholestasis, cirrhosis, hepatitis, or malignant degeneration to hepatocellular carcinoma[36]. Although ectopic liver tissue usually has normal histology of the liver, that is, normal portal structure, regular lobules, and central veins, ectopic liver tissue has an increased risk of hepatocellular carcinoma[27,43,53]. The reason for this increased risk of hepatocellular carcinoma in patients with ectopic liver tissue is unclear, it has been proposed that biliary drainage is insufficient and/or blood supply is reduced in the ectopic liver tissue[58]. Furthermore, many hepatocellular carcinoma cases are related to ectopic liver tissue, and are not associated with cirrhosis in the main liver. Arakawa and colleagues[62] reported that in 22 hepatocellular carcinoma cases related to ectopic liver tissue, only six cases (27%) had cirrhosis in the main liver.

It has been revealed that many authors have misinterpreted the results of the article by Yamashita and colleagues[78]. One of the most important reasons for this misinterpretation is that the article is written in Japanese. Another reason is that the authors copy each other directly without carefully reading the authors’ results[2,3,5,12,17,23,26,28,29,35,36,59,62]. In the review by Yamashita and colleagues[78], 70 cases of ectopic liver were reported in the literature up to 1985. One (4.5%) of 22 cases with ectopic hepatic tissue attached to the gallbladder developed hepatocellular carcinoma while eight (16.7%) of 48 cases with ectopic hepatic tissue located outside the gallbladder developed hepatocellular carcinoma. As a result of the statistical analysis carried out using the Yamashita and colleagues data, no statistically significant difference was found between ectopic liver tissue located on the gallbladder surface and its location outside the gallbladder in terms of hepatocellular carcinoma risk (P = 0.25). Many studies have suggested that ectopic liver tissue on the gallbladder is less susceptible to hepatocellular carcinoma development than ectopic liver tissue outside the gallbladder. A possible explanation proposed for this difference is that ectopic hepatic tissue attached to the gallbladder is an anomaly occurring later during the development of the biliary bud and is; therefore, well-differentiated[12,26,59,62]. However, the results of our analysis using the Yamashita and colleagues data[78] revealed that there was no difference. In the 72 articles reviewed in this study, including 91 patients with ectopic liver tissue attached to the gallbladder, only one patient reported having hepatocellular carcinoma in the ectopic liver tissue (1.09%).

CONCLUSION

Ectopic liver tissue is a rare developmental anomaly usually detected incidentally during surgery or autopsy. While it is often asymptomatic, it has a risk of malignant transformation and carries the potential for other complications such as bleeding and torsion. Although most studies have suggested that ectopic liver located outside the gallbladder has a higher risk of hepatocellular carcinoma, this is not reflected in the statistical analysis results.

ARTICLE HIGHLIGHTS
Research background

Liver tissue situated outside the liver with a hepatic connection is usually called an accessory liver, and that without a connection to the mother liver, is called ectopic liver tissue. Ectopic liver tissue is a rare developmental anomaly usually detected incidentally.

Research motivation

Although a limited number of case reports on ectopic liver tissue on the gallbladder surface or gallbladder mesentery have been published to date, no systematic literature research has been conducted.

Research objectives

While the main objective of this study was to review the articles published in the medical literature on ectopic liver tissue on the gallbladder surface or gallbladder mesentery, the secondary objective of this study was to present the medical history of two patients diagnosed with ectopic liver tissue.

Research methods

A systematic literature search was conducted on PubMed, Medline, Google Scholar, and Google databases using the following keywords: Accessory liver lobe, aberrant liver tissue, ectopic liver tissue, ectopic liver nodule, heterotopic liver tissue, hepatic choristoma, heterotopic liver tissue on the gallbladder, and ectopic liver tissue on the gallbladder. The search included articles published before June 2020 with no language restriction.

Research results

A total of 72 articles were identified involving 91 patients, 62 females and 25 males; no gender data were available for the remaining four patients. The age of these 87 patients ranged from five days to 91 years; this information was unavailable for the remaining four patients. Eleven patients had a history of various liver diseases, while 12 patients had no liver disease. Forty-nine patients had surgery for chronic cholecystitis and/or cholelithiasis, while 14 patients had surgery for a presumed diagnosis of acute cholecystitis. The remaining 28 patients underwent laparotomy for unrelated reasons. Sixty-one patients underwent laparoscopic cholecystectomy and 11 underwent open cholecystectomy. The remaining 19 patients underwent cholecystectomy and various surgical procedures such as autopsy, liver transplantation, living donor hepatectomy, Whipple procedure, and liver segment V resection.

Research conclusions

Ectopic liver tissue is a rare developmental anomaly usually detected incidentally during surgery or autopsy. While it is often asymptomatic, it has a risk of malignant transformation and carries the potential of other complications such as bleeding and torsion.

Research perspectives

First, a review of the literature and our clinical experience suggest that ectopic liver tissue-like lesions around the liver should be considered in the differential diagnosis of ectopic hepatocellular carcinoma, especially in patients with chronic liver disease. Therefore, even when the macroscopic appearance is normal, all ectopic liver tissue specimens should be sent for routine histopathological examination. Second, although most studies have suggested that ectopic liver located outside the gallbladder has a higher risk of hepatocellular carcinoma, this is not reflected in the statistical analysis results.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: Turkey

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C, C

Grade D (Fair): D

Grade E (Poor): 0

P-Reviewer: Mizuguchi T, Ooi L, Wang G S-Editor: Fan JR L-Editor: Webster JR P-Editor: Li JH

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