Biliary atresia with ectopic thyroid in the porta hepatis: a case report and literature review

Introduction

Ectopic thyroid is a rare developmental anomaly defined as the atypical presence of thyroid tissue in atypical anatomical positions. Although the pathogenesis remains unclear, it is believed to be due to abnormal embryonic development. Ectopic thyroid mostly develops from the blind hole of the tongue in the midline of the neck to the position near the midline of the sternal notch. It is more common in the neck (tongue, trachea, larynx, and esophagus) region and mediastinum and rarely in the liver, spleen, adrenal gland, pancreas, and other body regions.

Biliary atresia (BA) is a common cause of neonatal obstructive jaundice and severe hepatobiliary disease in infants. It is a progressive inflammatory disease with unknown etiology that affects the bile ducts inside and outside the liver, resulting in cholestasis, progressive hepatic fibrosis, and even cirrhosis, consequently endangering the lives of children. Without timely treatment, most children die within 2 years (1). Here, we present a rare case involving an infant with BA wherein ectopic thyroid tissue was incidentally discovered in the porta hepatis after the Kasai operation. We present this article in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-24-307/rc).

Case presentation

A 2-month-old boy developed yellowing of the skin and sclera 1 day after birth. Liver function tests performed at the local hospital 1 month before the current admission yielded the following results: total bilirubin (TBil), 202 µmol/L; direct bilirubin (DBil), 86.4 µmol/L; indirect bilirubin (IBil), 115.6 µmol/L; alanine transaminase (ALT), 33 U/L; aspartate transaminase (AST), 119 U/L; gamma-glutamyl transpeptidase (γ-GT), 341 U/L; and total bile acids (TBA), 73.1 µmol/L. Jaundice partially subsided with symptomatic treatment, including gamma globulin, received at the local hospital.

Fifteen days before the admission, his stool appeared light yellow, with no noticeable changes in urine color. The patient was referred to Tianjin Children’s Hospital for further examinations. B-ultrasound at our clinic revealed a bilateral oblique hernia, bilateral testicular hydrocele, and umbilical hernia. The patient was admitted to our Department of Gastroenterology for unexplained jaundice. Physical examination showed: temperature, 36.9 ℃; pulse, 135 beats/min; respiratory rate, 30 breaths/min; blood pressure, 80/50 mmHg; weight, 6.2 kg; body length, 56 cm; head circumference, 39 cm; chest circumference, 38 cm; and abdominal circumference, 39 cm. No abnormalities were found in the head, neck, and chest. The liver was palpable 3 cm below the ribs with blunt margins and a medium texture. The spleen was not palpable. An approximately 5 cm × 5 cm cystic bulge was observed in the umbilicus, retractable by pressure. Bilateral scrotal enlargement and palpable masses in the bilateral inguinal region were observed.

After admission, all tests were completed. Electrolytes were generally normal. Venous blood gas analysis showed a pH of 7.344, partial pressure of carbon dioxide of 35.8 mmHg, and a blood base excess of −5.6 mmol/L, suggesting metabolic acidosis. Routine blood tests revealed: hemoglobin, 107 g/L; white blood cells (WBCs), 10.48×10⁹/L; neutrophils, 14%; lymphocytes, 72%; monocytes, 8%; eosinophils, 6%; platelets, 344×10⁹/L; and C-reactive protein, <2.5 mg/L. Coagulation function tests indicated an activated partial thromboplastin time of 45.2 s and a fibrinogen level of 1.453 g/L, with other values within the normal range. Liver function tests showed TBil, DBil, IBil, ALT, AST, and γ-GT levels of 145.6 µmol/L, 118.3 µmol/L, 27.3 µmol/L, 67 U/L, 148 U/L, and 492 U/L, respectively. Thyroid function tests showed a thyroid-stimulating hormone (TSH) level of 6.093 mIU/L, whereas serum total triiodothyronine (TT3), total thyroid hormone (TT4), free triiodothyronine (FT3), and free thyroid hormone (FT4) was 1.93 nmol/L, 110.41 nmol/L, 4.75 pmol/L and 11.66 pmol/L, respectively. TORCH antibody detection test showed an Epstein-Barr virus (EBV)-immunoglobulin G (IgG) titer of 28.33 AU/L, with negative results for other antibodies. Coxsackie virus antibodies were not detected. Routine urine analysis showed: occult blood, 3+; protein, 4+; glucose, ±; and ketone body, ±. Centrifugation microscopy showed: red blood cells (RBCs), 2–3/high power field (HPF); WBCs, 0–1/HPF. These findings raised suspicion of infection, but the subsequent two follow-up urine routine tests were normal, and all three urine cultures yielded negative results.

Echocardiography revealed a patent foramen ovale (3 mm) and patent ductus arteriosus (2 mm). B-ultrasound revealed poor gallbladder filling, irregular gallbladder wall, and the common bile duct was not detected (Figure 1). Polyene phosphatidylcholine and ademetionine 1,4-butanedisulfonate injections were administered for liver protection. On the third day of admission, the patient developed a fever and received latamoxef sodium for infection. On the sixth day of admission, repeat B-ultrasound showed poor gallbladder filling, absence of the common bile duct, and multiple enlarged lymph nodes at the porta hepatis (Figure 2). Liver function tests showed TBil, DBil, IBil, ALT, AST, and γ-GT levels of 173.9 µmol/L, 115.8 µmol/L, 58.1 µmol/L, 118 U/L, 322 U/L, and 671 U/L, respectively. Due to the lack of noticeable improvement with medical treatment, the patient was transferred to the general surgery department on day 10 of admission as obstructive jaundice could not be excluded, and stool color became lighter.

Figure 1 The common bile duct is not detected during B-ultrasound examination.

Figure 2 B-ultrasound examination shows multiple enlarged lymph nodes at the porta hepatis.

On day 12 of admission, the patient underwent laparoscopic exploration of the gallbladder, common bile duct, and liver biopsy. After adequate anesthesia, the surgical area was disinfected, and a 5 mm incision was made on the left side of the umbilical rim. Carbon dioxide insufflation created a pneumoperitoneum using a pneumoperitoneum needle. A 5.5 mm trocar was inserted through the umbilical incision once the pneumoperitoneum pressure reached 10 mmHg, allowing for the insertion of a laparoscope. A small amount of yellow-green ascites was observed during abdominal cavity exploration. The liver appeared enlarged, granular, and firm. Dysplasia and poor gallbladder filling were noted. Two additional 5.5 mm trocars were placed in the right mid-abdomen and right upper abdomen, respectively, and liver tissue was collected for frozen section examination. The top of the gallbladder was freed and raised into the hole created by the trocar in the right upper abdomen, revealing white bile upon opening. A No. 6 tube was inserted for bile duct flushing, and no obvious yellow or green bile was observed. Cholangiography was performed to visualize the gallbladder and common bile duct. However, the common hepatic duct and the right and left hepatic ducts were not visualized (Figure 3). Hepatic cytopathology indicated bile duct hyperplasia, fibrous tissue hyperplasia, and visible bile emboli, consistent with extrahepatic biliary tract obstruction. An incision was then made under the right costal margin, and the gallbladder was removed. The fibrous tissue was detached from the hepatic hilum upward, removing approximately 2 cm of fibrous plaque tissue surrounding the hepatic hilum, revealing a small amount of bile flow at points 11 and 2 in the hepatic hilum. Compression and hemostasis were applied, and the distal end of the high jejunum was severed 25 cm below the duodenal ligament. The intestinal lumen was closed distally, and end-to-side jejunojejunostomy was performed 40 cm downstream from the proximal jejunum to the distal jejunal section. The distal end of the jejunum was lifted from the transverse colonic mesentery, and a hilar-jejunal end-lateral anastomosis was performed with the hepatic portal.

Figure 3 The common hepatic duct and the right and left hepatic ducts cannot be visualized during cholangiography.

Pathological findings

Three specimens were submitted for analysis; a dark green, wedge-shaped liver biopsy, the gallbladder, and a fibrous plaque, measuring 0.6 cm × 0.4 cm × 0.2 cm, 3 cm × 0.7 cm × 0.3 cm, and 0.8 cm × 0.5 cm × 0.4 cm, respectively. Histopathological examination revealed swollen and cholestatic liver cells. Bile plugs were found in the capillary bile ducts, the portal area was significantly widened, the bile ducts and fibrous tissues were obviously proliferated, and pseudolobules of the liver were formed (Figure 4). That the liver also has ductal plate malformation, characterized by irregular shape of the bile ducts and blocked lumens (Figure 5). The gallbladder was poorly developed. The fibrous plaque consisted of fibers, blood vessels, nerves, and ectopic thyroid tissue (Figure 6), which contained follicular cells and colloids mixed with multiple lymphocytes. The diameter of ectopic thyroid tissue was approximately 2 mm. Immunohistochemical staining showed strong expression of PAX-8, thyroid transcription factor-1 (TTF-1), and thyroglobulin (TG) (Figure 7).

Figure 4 Histopathological examination shows pseudolobules of the liver (hematoxylin and eosin, 4×).

Figure 5 Immunohistochemical staining of CK19 shows ductal plate malformation of liver (10×). CK19, cytokeratin 19.

Figure 6 Histopathological examination shows ectopic thyroid tissue in a fibrous plaque from the porta hepatis (hematoxylin and eosin, 4×).

Figure 7 Immunohistochemical staining shows strong expression of TG (4×). TG, thyroglobulin.

Pathological diagnosis

BA with ectopic thyroid in the porta hepatis.

Postoperative course

Liver function re-examination post-operatively showed no improvement (Table 1). Three months later, liver transplantation was performed at another hospital.

Literature search

We reviewed literature from 1960 to 2022 and identified six relevant case reports of ectopic thyroid in the porta hepatis (Table 2). However, no literature was found using “biliary atresia” and “ectopic thyroid in the porta hepatis” as search terms.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s legal guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

The thyroid gland develops embryonically on day 24 of gestation (2), originating primarily from the endoderm between the midline of the original pharyngeal wall and the first pair of pharyngeal bursae. It consists of thyroid follicular cells producing thyroid hormones and parafollicular or C cells producing calcitonin. When the thyroid fails to descend to the final position in front of the trachea, it is called an ectopic thyroid.

The prevalence of ectopic thyroid is approximately 1 per 100,000–300,000 persons (3). About 700 cases have been documented worldwide, indicating the rarity of this developmental anomaly (4). Most of ectopic thyroids cannot be evaluated due to asymptomatic patients and incidental detection.

Ectopic thyroid can be divided into aberrant thyroid and accessory thyroid. During embryonic development, when the thyroid primordium completely stops moving, all thyroid tissues exist in abnormal positions, and no thyroid tissues can be found in the standard anatomical parts of the neck; the condition is called aberrant thyroid. If the thyroid gland is in the expected location in the neck and additional thyroid tissue is found in other parts of the body, the condition is called accessory thyroid. The present case belonged to the latter category. Ectopic thyroid can appear in almost any part of the body, although it is more common at the base of the tongue and the front of the neck; ectopic thyroid at the base of the tongue accounts for approximately 90% of cases (5), while that in the neck and other parts of the body account for 10% cases. The condition shows female predominance. Common sites in the head and neck region include the trachea, submandibular region, lateral cervical region, palatine tonsils, carotid bifurcation, iris, and pituitary gland (6). Other sites include the axilla (7), mediastinum (8), heart (9), and ascending aorta (10). Common sites in the gastrointestinal system are the esophagus (11), stomach (12), duodenum (13), gallbladder (14), liver (15), hepatic portal (16), pancreas (17), and mesentery of the small intestine (18). The adrenal glands (19), spleen (20), and the genital organs also show involvement.

Ectopic thyroid in the porta hepatis is extremely rare, and only six cases have been reported thus far (4,16,21-24). Five of them were females, and the median age was 58 years old. Two cases were found by accident, whereas two presented with chronic abdominal discomfort and abdominal pain. Imaging examination showed tumors in the porta hepatis measuring between 4.3 and 10 cm. One case involved a male fetus with trisomy 18 who was induced in the 30^th weeks of gestation, ectopic thyroid in the porta hepatis, which showed a diameter of approximately 2 mm, was accidentally found during autopsy. To our knowledge, cases of BA complicated by ectopic thyroid in the porta hepatis have not previously been reported.

The mechanism underlying ectopic thyroid formation remains unclear. The most common mechanism is inadequate or excessive migration; hence it is usually located along the path of thyroid gland’s descent (25). Ectopic thyroid tissue in the abdomen is rare and unlikely associated with aberrant migration, because it is far away from embryological development path of thyroid gland. Since most intra-abdominal organs, similar to thyroid, arise from the endodermal germ layer, heterotopic differentiation of precursor cells from the foregut endoderm is the commonly believed mechanism (26). Ectopic thyroid tissue in the adrenal gland is an exception, because the cortex and medulla of adrenal gland originate from the mesodermal layer and ectodermal layer respectively (27). Some scholars believe that ectopic thyroid is a particular type of teratoma. Mutations in genes, such as FOXE1, PAX-8, and TTF-1 may cause thyroid dysplasia (28). The differential diagnosis of ectopic thyroid tissue in the porta hepatis includes hilar cholangiocarcinoma and lymphoma. In addition, it is necessary to exclude the metastasis of thyroid carcinoma to the porta hepatis. The distant metastasis sites of thyroid carcinoma, including pancreas, porta hepatis and liver, have been reported. Therefore, further examinations of thyroid gland and lymph nodes in neck are necessary (17). Nodular goiter or malignant transformation can also occur in ectopic thyroid tissue.

We found that the clinical treatment of ectopic thyroid depends on the patient’s age, thyroid function test results, severity of symptoms, size and location of the ectopic thyroid, results of pathological examination, and presence or severity of complications. When a newborn or an infant is diagnosed with ectopic thyroid, such as this case, a clinical imaging examination should be conducted promptly to ascertain the presence of a normal thyroid gland in the cervical region and to monitor the child’s thyroid function. If hypothyroidism is present, thyroid hormone replacement therapy should be administered immediately to avoid growth and mental retardation (29). Cases with no clinical symptoms, normal thyroid function, and a small ectopic thyroid tissue can be observed without treatment. For complications of ectopic thyroid (severe obstruction, bleeding, ulceration, cystic degeneration, or malignancy), surgical resection should be considered on the premise that normal thyroid tissue exists.

Conclusions

Ectopic thyroid is a rare disease, with ectopic thyroid in the porta hepatis extremely rare. For adults, it is essential to rule out a metastatic origin from occult thyroid carcinoma. For infants, ectopic thyroid is the leading cause of congenital hypothyroidism, and if hypothyroidism is present, thyroid hormone replacement therapy should be administered promptly.

Acknowledgments

Funding: This work was supported by the Tianjin Applied Basic Research Project (No. 22JCZDJC00290) and Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-040A).

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-24-307/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-307/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-307/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s legal guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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