Ectopic Liver Tissue Associated With the Gallbladder: Two Unique Patients and a Literature Review

Introduction

Ectopic/accessory liver tissue is a rare developmental anomaly thought to be due to abnormal development of the liver during embryogenesis. The exact incidence is not known; however, a few studies have reported an incidence of 0.09%-0.47%.^1,2 Most patients with ectopic liver tissue are asymptomatic, and the condition is usually discovered incidentally during intraabdominal surgery or autopsy. In rare symptomatic cases, patients may present with a range of issues, from mild liver function test abnormalities to severe abdominal pain or discomfort secondary to torsion and ischemia. Here, we report 2 patients with ectopic liver tissue identified incidentally during cholecystectomy; one with sickle cell congestion and the other with steatohepatitis. To the best of our knowledge, ectopic liver tissue with sickle cell congestion has not been reported previously.

Case Reports

The first patient was a 35-year-old Black woman with sickle cell trait who presented to the Emergency Department with severe abdominal pain. Six months prior, she had 2 encounters in the Emergency Department, both involving nausea, vomiting, and significant abdominal pain. Abdominal examination revealed right upper quadrant tenderness, and abdominal ultrasonography confirmed a 2.7 cm stone in the gallbladder. Murphy's sign was identified, consistent with acute cholecystitis. The patient's liver function test results, including aminotransferases and bilirubin, were within the reference range. Other laboratory studies, including complete blood cell count, lipid profile, and blood glucose were all within the reference range. The patient was diagnosed with acute cholecystitis associated with cholelithiasis. The patient opted for an emergent cholecystectomy.

During the procedure, the surgeon reported finding an inflamed gallbladder, a large stone, and a small dark red mass with an appearance similar to a “splenule” (Figure 1A). The mass was found close to the gallbladder neck and had no biliary or vascular connections to the liver. The whole specimen was submitted for pathology review, and gross examination showed a gallbladder with areas of edema and a 2.9 cm green-yellow ovoid stone. In addition, a 1.7 cm “lymph node” was identified, and this structure was serially sectioned and submitted entirely for histological analysis. The cholecystectomy specimen showed features consistent with acute and chronic cholecystitis with cholelithiasis. The dark red tissue, which was suspected by the surgeon to be a “splenule” and was identified as a “lymph node” by the pathologist, turned out to be ectopic liver tissue consisting of circumscribed liver tissue with hepatic cords. The sinusoids were dilated and congested with sickled red blood cells (Figure 1C and D). The portal tracts showed mild chronic inflammation with no evidence of malignancy.

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Figure 1.

Patient 1: (A, B) grossly, inflamed gallbladder, and a small dark red mass with a similar appearance to a “splenule” were seen. (C) Lower power picture showing liver tissue with cords of hepatocytes and congested sinusoids (H&E, ×10). (D) The sinusoids were dilated and congested with sickled red blood cells (H&E, ×40). Abbreviation: H&E, hematoxylin and eosin.

The second patient was a 52-year-old White man with a history of coronary artery disease, familial hyperlipidemia, and type 2 diabetes. On his annual health visit, he reported having right-sided abdominal pain exacerbated by fatty or spicy food. Based on his low ejection fraction (13%) on hepatobiliary iminodiacetic acid (HIDA) scan results, he was diagnosed with biliary dyskinesia and was scheduled for elective cholecystectomy. Nine days later, the patient presented to the Emergency Department for right upper quadrant abdominal pain, nausea, and vomiting. Abdominal ultrasonography results were negative for Murphy's sign and positive for a 6 mm “gallbladder polyp” and hepatic changes consistent with steatosis and hepatitis. The patient's liver function tests showed elevated bilirubin, aspartate transaminase (53 IU/L; reference range <35 IU/L), and alanine transaminase (66 IU/L; reference range <52 IU/L).

During the laparoscopic cholecystectomy, the surgeon noticed a nodular liver and a “chronic rind likely from chronic cholecystitis.” The surgeon considered the ectopic liver tissue to be a lymph node, and no intraoperative images were taken. The surgical specimen was submitted for pathology review. Gross examination revealed a 0.9 cm “lymph node” attached to the gallbladder. On histological analysis, the gallbladder showed mild chronic cholecystitis, and interestingly, the suspected lymph node showed circumscribed liver tissue with macrovesicular steatosis, ballooned hepatocytes, and lobular necro-inflammatory activity consistent with features of steatohepatitis (Figure 2A and B).

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Figure 2.

Patient 2: (A) circumscribed liver tissue with steatosis (H&E, ×2). (B–D) macrovesicular steatosis, ballooned hepatocytes, and lobular necro-inflammatory activity consistent with features of steatohepatitis (B—H&E, ×10; C and D—H&E, ×40, arrow: ballooned hepatocyte, arrowhead: Mallory-Denk body). Abbreviation: H&E, hematoxylin and eosin; arrow, macrovesicular steatosis; arrowhead, ballooned hepatocyte.

Discussion

Accessory or ectopic liver tissues were first described by Morgagni in 1767 and by Corsy in 1922.^3,4 While unusual hepatic tissues connected to the liver (such as by a stalk) are defined as accessory liver lobes, hepatic tissue isolated outside the liver with no direct connection to the main organ is defined as ectopic liver tissue. Both anomalies are most commonly reported in association with the gallbladder; however, ectopic liver tissue has been reported to occur at various other intraabdominal sites, such as the gastrohepatic ligament, umbilicus, adrenal glands, or pancreas, as well as extra-abdominally in the thoracic cavity.^5,6 These tissue structures are likely due to aberrant migration of liver tissue during embryologic development. ⁷

As has been reported previously, our patients both had ectopic liver tissue with histologic architecture resembling normal liver alongside the presence of hepatic lobules, central veins, and portal tracts. However, this tissue is functionally and metabolically impaired, which may make it prone to carcinogenesis. ⁸ Although there are no detailed reports describing vascular supply and biliary drainage in ectopic liver tissue, the following 3 vascular supply patterns of ectopic liver tissue associated with the gallbladder have been reported: arteries arising from cystic artery ⁹ ; a vascular pedicle arising from liver parenchyma ⁷ ; and vascular structures embedded in a mesentery connecting the hepatic site to the ectopic liver tissue. ¹⁰ Biliary drainage has not been intraoperatively evident in most reports.^3,7 Similarly, in our patients, no biliary drainage connected to the main biliary system or cystic duct was evident.

Clinically, patients with sickle cell disease or trait may develop a spectrum of acute and chronic liver complications. Acute complications can include intrahepatic cholestasis, acute hepatic sequestration, and acute gallstone disease, while a chronic complication may be liver cirrhosis. Sickle cell hepatopathy commonly occurs in patients with sickle cell disease and less commonly in patients with sickle cell trait. Histologically, sinusoidal dilatation and congestion, cholestasis, ductular reaction, hepatic infarction, and cirrhosis have been reported in patients with sickle cell disease.^11,12 While our first patient was asymptomatic for manifestations of sickle cell disease, and her liver function tests were within normal limits, the ectopic liver tissue showed sinusoid dilatation and congestion with sickled red blood cells.

The second patient had mildly elevated transaminases, and he also had type 2 diabetes, hypercholesterolemia, essential hypertension, and coronary heart disease. Otherwise, he had no history of liver disease. Mildly elevated transaminases may be seen in association with steatohepatitis. However, for both of our patients, we cannot comment on the histologic manifestations of the main liver, since both were asymptomatic for hepatic disease and no further workup was pursued.

Our patients and several other case reports have shown that ectopic liver tissue can manifest histologic changes similar to the main liver; such as fatty change, hepatitis, cholestasis, cirrhosis, and hepatocellular carcinoma (HCC).^3,4 However, ectopic liver tissue with sickle cell congestive hepatopathy has not been previously reported. Strangely, our patient had no symptoms of sickle cell crisis, and moreover, the patient had only sickle cell trait, not disease. This finding supports the notion that ectopic liver tissue does not have a fully developed vascular supply as in the normal liver, and it is possible that vulnerable red blood cells had been sickled within the compromised vascular supply of the ectopic liver tissue, leading to congestion.

Histologically, the ectopic liver tissue from both of our patients reflected their underlying medical conditions. However, we do not know whether our patients’ livers shared histological features similar to the ectopic tissue. Arakawa et al ¹ identified ectopic liver tissue in the autopsy of a patient with alcohol use disorder in which both the main liver and the ectopic tissue had changes consistent with alcoholic cirrhosis. However, histological findings in ectopic liver tissue do not always correlate with the main liver. Greenberg et al ¹³ reported a patient who had radiological evidence of fatty liver disease but ectopic liver tissue with normal liver histology. A similar observation was reported by Malhas et al, ¹⁴ in which a patient had ectopic liver tissue with normal liver histology within the context of gallbladder disease and fatty liver. Lastly, Hamdani et al ¹⁵ reported a patient with a 12-year history of ulcerative colitis who underwent liver transplantation in which the explanted liver showed biliary cirrhosis while ectopic liver tissue had rare bile ducts and no features of biliary cirrhosis.

Ectopic liver tissue attached to the gallbladder may be related to the development of biliary diseases, such as cholelithiasis and acute or chronic cholecystitis. However, this correlation may be due to ectopic liver tissue being diagnosed more commonly during cholecystectomy and because the gallbladder is the most common location of both ectopic and accessory liver tissue. ⁹

Several case reports have shown ectopic liver tissue within the context of other congenital anomalies such as biliary atresia, agenesis of the caudate lobe, omphalocele, bile duct cyst, and cardiac and conotruncal anomalies^16–19; however, these cases were reported in neonates and fetuses, and such abnormalities have not been reported in adult patients where ectopic liver tissue was incidentally discovered during cholecystectomy.^3,16

Some reports have suggested that patients with ectopic liver tissue may be at an increased risk of HCC. In a review by Yamashita et al, ²⁰ 70 patients with ectopic liver tissue had been reported in the literature up to 1985. The authors reported that 1 (4.5%) of 22 patients with ectopic liver tissue attached to the gallbladder developed HCC while 8 (16.7%) of 48 patients with ectopic hepatic tissue located outside the gallbladder developed HCC. Arakawa et al ¹ reported 22 cases of HCC in extrahepatic tissue, mostly in patients from Japan, 1 of whom was their patient. Out of these, only 6 (27%) patients had cirrhosis in the main liver, and none of the patients had HCC in the main liver. According to their findings, noncancerous extrahepatic tissue was found in only a few patients. But whether patients with ectopic liver tissue truly have an increased risk of HCC is unclear, since only a small number of cases have been reported, and it is a rare condition. Notably, insufficient or altered biliary drainage and/or blood supply of the ectopic liver tissue has been suggested as a predisposing factor for HCC. But as Arakawa et al suggest, noncancerous liver tissue has been found in only a few patients who had HCC in ectopic liver tissue; therefore, some of these cases may represent hepatoid carcinoma of extrahepatic origin rather than HCC arising in the ectopic liver tissue.

Regarding care and treatment, whether patients with radiologically diagnosed ectopic/accessory liver tissue should receive surgical intervention remains a question. Only very few case reports are available to inform treatment approaches, and the literature is difficult to assess because the terms ectopic and accessory liver tissue have been used interchangeably. However, ectopic liver tissue is almost always an incidental finding; therefore, when patients are asymptomatic with no other liver function abnormalities or underlying conditions, surgical intervention would likely not be necessary. However, we note that although this hepatic structure is extremely rare, it may harbor the possibility of severe liver injury within the setting of vaso-occlusive events in patients with sickle cell disease/trait or other high-risk factors, and this could warrant surgical intervention. Overall, physicians may expect to encounter more cases of ectopic liver tissue because of the increasing use of new sophisticated imaging techniques.

Conclusion

Ectopic liver tissue is a rare, potentially under-recognized clinical entity that is usually identified as an incidental finding during surgery or imaging. Patients with ectopic liver tissue are usually asymptomatic, and complications such as torsion, hemorrhage, or HCC associated with ectopic liver tissue have rarely been reported.