EL is a rare condition. The first published case dates back to 1922.1,5
The diagnosis is uncommon, and there are fewer than 80 documented cases of EL.2
The real incidence of EL attached to the gallbladder wall is difficult to assess but is reportedly 0.24–0.47% of the population though as with other sites, most of the cases of EL attached to the gallbladder are diagnosed at laparotomy, laparoscopy or during an autopsy. By 2007, 61 cases had been reported.4,6,8–14
Even though the gallbladder is the main site for the development of EL, this finding is still exceptional. In 1940 in a review of 5500 autopsies, only 0.05% had EL and in only three cases was this attached to the wall of the gallbladder. More recently, a review of 1060 laparoscopic procedures found EL attached to the gallbladder wall in three patients (0.28%).10
EL is most frequently described in Asia and to the best of our knowledge, our case is only the second case of EL attached to the gallbladder described in South America.16
Collan et al.3
divided EL tissue into four distinct categories: (a) EL that is not connected to the main liver and is usually attached to the gallbladder or intra-abdominal ligaments; (b) microscopic ectopic liver found occasionally in the gallbladder wall (as in the patient discussed here); (c) a large accessory liver attached to the “mother” liver by a stalk; and (d) a small accessory liver lobe attached to the main liver.
Several theories have been proposed to explain the presence of EL at different locations.9
Most researchers believe that the cause of EL is an aberrant migration during the embryologic development of the liver.4
During the fourth week in utero, the liver and biliary system originate from the hepatic diverticulum in the direction of the septum transversum. Abnormalities of this migration or a displacement of a portion of the cranial part of the hepatic diverticulum of the liver bud to other sites may be the main cause of EL.1,2
The close relationship of the developing hepatic parenchyma cell cords to the pars cystica may explain why ectopic hepatic tissue could be found in the wall of the gallbladder.1,2,9
Although the EL is usually attached to the serosa of the gallbladder or lies within its wall, it can also occur in the gallbladder lumen.
EL is sometimes associated with other congenital anomalies, such as biliary atresia, agenesis of the caudate lobe, omphalocele, bile duct cysts or cardiac anomalies; however, these abnormalities are not present when the heterotopic tissue is attached in the surface of gallbladder wall9
. EL attached to the gallbladder usually remains asymptomatic and is occasionally discovered during laparoscopy, as was the case with the patient in the present report. When symptomatic, the principal complaint is usually upper abdominal pain due to complications such as torsion, hemorrhagic necrosis, rupture or some form of compression by the mass due to malignant transformation to HCC.5,10,11,13,16
The differential diagnosis of lesions attached to the gallbladder includes other diseases that lead to a mass effect, such as carcinoma of the gallbladder, polyps, accessory liver, adenomyomatosis, hyperplastic lymph nodes and metastatic disease.
Detection of EL tissue before surgical intervention or autopsies by means of imaging studies is rare.2,10
This may be due to the small size of most EL, the lack of awareness of this unusual condition among radiologists, difficulty interpreting the imaging and the frequent lack of symptoms 2. The diagnosis of EL should be considered when radiologists identify a soft tissue mass on the gallbladder wall on imaging (whether ultrasound, CT scan, or MRI), or as an incidental finding during laparoscopy. Percutaneous biopsies should be avoided because of the risk of bleeding and the possibility of malignant degeneration to HCC. To the best of our knowledge, a preoperative diagnosis of gallbladder-associated EL was made in only two reported cases.2,4
In the patient described in the present report, the ultrasonographic examination before surgery showed only a slight thickening of the anterior wall of the gallbladder, insufficient to suggest EL.
The histological findings of EL tissue are similar to those of the liver proper, including regular lobules, a central vein, and normal portal spaces. In some cases, it is possible to observe an increase in the number of blood vessels in the outer surface of the gallbladder attached to the ectopic liver tissue similar to what was observed in our patient. As in the liver itself, EL attached to the gallbladder can show fatty infiltration, cholestasis, hepatitis, hemosiderosis, cirrhosis, or malignant degeneration to HCC.2,4,6,11,13,15
In our patient there was mild steatosis and posterior focal areas of hemosiderosis confirmed by specific staining for iron pigments.
There has been evidence to suggest that ectopic liver is at increased risk of developing HCC.9,15
Arakawa et al.17
found 21 cases in the literature, mostly from Japan, of HCC arising extra-hepatically. These authors suggest that ectopic tissue is more susceptible to the development of malignancy because it does not have a complete vasculature or ductal system like a normal liver, and is perhaps functionally impaired. This altered hepatic function may lead to chronic inflammation or cirrhosis, which increases the possibility of developing HCC. Yamashita et al.18
reviewed 70 cases of ectopic liver reported in the literature before 1986, including nine cases of HCC originating in EL tissue. Of 48 cases (excluding those localized to the gallbladder), 22 developed HCC,17
contrasting with only one of 42 cases of EL attached to the gallbladder. A possible explanation for this difference is that EL attached to the gallbladder is an anomaly occurring later during the development of the biliary bud and is therefore well differentiated.9
Despite the presence of steatosis and areas of hemosiderosis, we could not find any evidence of malignant degeneration in the patient in this report. However, due to the perceived risk of malignant degeneration in EL generally, resection of the EL en bloc with the gallbladder is strongly recommended.2
With the increase in laparoscopic cholecystectomy, more cases of EL attached to the gallbladder have been identified in recent years and are easily removed using this approach, preferably inside a bag, and then carefully examined by a pathologist. If the histopathological examination confirms the presence of an invasive HCC, a further surgical intervention should be considered, to extend the hepatic margins of resection and perform a regional lymphadenectomy.