Intraductal papillary neoplasm of bile duct: all rare in one

Abstract

A 45-year-old woman was referred from Department of Dermatology to Surgery outpatient department with pruritus since 6 months and an episode of jaundice that lasted for 15 days about 6 months ago. She was referred with a contrast-enhanced MRI finding that showed a small lesion in the lower end of common bile duct. Endoscopy-guided biopsy was performed twice at our hospital, the second revealed low grade dysplasia. Consequently, she underwent pancreaticoduodenectomy. Intraoperatively, there were both vascular and biliary anatomical variations that were missed on preoperative images. On histopathological examination, it turned out to be a mixed variety of intraductal papillary neoplasm of bile duct (IPNB). As all findings were rare in one, hence, we present this case of IPNB that presented to us with variable clinical, radiological, surgical and pathological findings.

Background

Biliary tract malignancies usually arise spontaneously without any precursor lesion. However, occasionally intraductal non-invasive lesions may be identified accompanying adenocarcinoma. According to the 2010 WHO classification, intraductal papillary neoplasm of bile duct (IPNB) is one such entity.¹ It includes intraductal papillary cholangiocarcinoma and similar precursor lesions as well. It usually presents in age group between 50 and 70 years and has male predominance.² The usual complaints include features of obstructive jaundice (like biliary colic, icterus and occasionally fever).² However, we present a case of IPNB which presented with all the surprises such as unusual history, imaging, difficulty in preoperative diagnosis, challenges during surgery and histological surprise.

Case presentation

A 45-year-old woman was referred from a different hospital (department of dermatology) to our hospital (surgery outpatients department) with generalised pruritus for the last 6 months. She presented with a contrast-enhanced MRI finding that showed a small enhancing soft tissue at the lower end of common bile duct (CBD). On further probing, she revealed the history of yellowish discolouration of eyes which lasted for a fortnight about 6 months ago. However, there was no history of weight loss, clay coloured stool and high coloured urine. On examination, she was haemodynamically stable, well nourished and ECOG 1 (performance status). There was no icterus and her abdominal examination revealed palpable, non-tender gall bladder.

Investigations

Her complete blood count and renal function tests were within normal limit. Liver function tests showed normal bilirubin level, coagulation profile and serum albumin/globulin levels. However, liver enzymes were slightly elevated: aspartate amino transferase was 109 IU/L and alanine amino transferase was 110 IU/L. Her alkaline phosphatase was markedly elevated to 1388 IU/L as was CA 19–9 which was raised to 109 U/mL. Ultrasonography of the abdomen showed dilated CBD (12 mm) and mild intrahepatic biliary radicle dilatation (IHBRD). Her contrast-enhanced CT (CECT) of the abdomen revealed ill marginated hypo enhancing 13×15 mm mass lesion involving ampullary region with abrupt cut-off at distal CBD and double duct sign (dilatation of CBD and main pancreatic duct) with IHBRD. Her contrast-enhanced MRI showed minimal central IHBRD. Axial T2-weighted image showed two hyperintense rounded structures in one section only, which was interpreted as due to tortuosity as both proximal and distal images showed a single lumen (figure 1). Arterial variant anatomy was not visualised on the available venous phase contrast-enhanced images. She underwent side viewing endoscopy and biopsy twice. The second biopsy showed a few villi form structures representing adenoma with low grade dysplasia. The case was discussed with multidisciplinary team. Owing to the presence of mass in the lower end of CBD and a preoperative biopsy suggestive of dysplasia, our preoperative clinicoradiological stage was T1N0M0. With these available findings an intraoperative frozen section was not considered, and she was planned for exploratory laparotomy and pancreaticoduodenectomy. The patient was informed about her clinicopathological findings and our plan for surgical intervention. A written and informed consent was obtained prior to the surgery (exploratory laparotomy and pancreaticoduodenectomy). MR cholangiopancreatography was not done prior to the surgery.

Figure 1.

Contrast-enhanced MRI of abdomen and pelvis. Arrow is showing two hyper intense rounded structures in T2-weighted image that was interpreted as tortuosity as both proximal and distal images showed a single lumen.

Differential diagnosis

Differential diagnosis for lower CBD lesions with diverse range of presentations are enumerated in table 1

Table 1.

Differential diagnosis for lower CBD lesions with diverse range of presentation

	Cholangiocarcinoma	Tuberculosis	IGG4-related disease
Demographics	Old (over 50 years), male predominant. Higher prevalence in Asia with chronic parasitic infestation	Common in Indian subcontinent and tropical countries	Older age (median age 50 years), male predominant
Clinical features	Painless, persistent progressive obstructive jaundice with a palpable gall bladder Loss of weight and loss appetite present	Painless progressive obstructive jaundice of chronic duration, Intermittent fever. Loss of weight and loss appetite present	Obstructive jaundice
Possible history (may be present)	Recurrent cholangitis.	Past surgical history of gastrojejeunostomy and truncal vegotomy Lymphnodes palpable in neck or axilla.	Diverse range of clinical presentation. Obstructive jaundice (most common) and gastrointestinal bleeding (rare). Single or multiple organs involved with diffuse or multiple swellings, nodules, and or hypertrophic lesions.
Blood or body fluid test	Non diagnostic	Suggestive: raised ESR Lymphocytosis. Peritoneal or pleural fluid: raised ADA	Suggestive: Serum IGG4 level elevated in 70% cases.
Imaging: lower CBD lesions	Intraductal tumour (papillary or polypoidal mass), proximal ductal dilatation, multifocal and relatively hypoattenuating. Bile duct wall thickening and enhancement.	Stricture and soft tissue lesion (pseudotumour) in lower CBD, with proximal ductal dilatation	Stricture and stenosis of bile duct
Preoperative biopsy (side view endoscopy and biopsy)	Diagnostic of adenocarcinoma	SVE with brush cytology, PCR for bile sample aspirated from bile duct, FNAC of lymphnode, CBNAAT positive of tissue biopsy	Difficulty in achieving preoperative diagnosis.
Histopathological examination	Moderate to well-differentiation adenocarcinoma, with glandular and tubular structure,	Granulomatous lesions in lower CBD lesion, granulomatous lymphadenitis, caseation necrosis, epitheloid granuloma formation. langhans giant cells	Lymphoplasmacytic infilteration positive for IGG4 immunostaining and fibrosis, and phlebitis. IgG4 positive plasma cells exceeding 10/HPF
Diagnosis	Clinicopathological diagnosis	Clinicopathological diagnosis + Response to antitubercular treatment (systemic symptoms improvement)	Histology, imaging, serology, other organ involvement and response to therapy

ADA, Adenosine deaminase; CBD, common bile duct; CBNAAT, Cartridge-based nucleic acid amplification test; ESR, Erythrocyte sedimentation ratio; FNAC, Fine-needle aspiration cytology; HPF, High-power field; PCR, Polymerase chain reaction; SVE, Side view endoscopy.

Treatment

The patient was planned for exploratory laparotomy with a possibility of pancreaticoduodenectomy. Intraoperatively, hepatic flexure mobilisation and kocherisation was done followed by isolation of infra pancreatic superior mesenteric vein. This was followed by portal dissection which included identification of the right hepatic artery lying lateral and posterior to portal vein. It was found to be originating from superior mesenteric artery (figure 2) and left hepatic artery arising from coeliac trunk. Gastroduodenal artery was identified and ligated. Pyloroduodenal junction was transacted using staple, and pancreas was transacted at the neck anterior to portal vein using harmonic shear scissors after creating a tunnel between the neck and superior mesenteric vein. Jejunum was transacted about 15 cm distal to the duodenojejunal junction and specimen was delivered into the lesser sac. CBD was traced superiorly and two different ducts visualised, one being a sectoral duct which joined at the junction of common hepatic duct and cystic duct. Both sectoral duct and common hepatic duct were transacted separately. Specimen was delivered after dissection of uncinate process from the portal vein (figure 3). Subsequently, pancreaticojejunostomy (Dunkin’s technique), two separate hepaticojejunostomies (figure 4) and gastrojejunostomy were done along with feeding jejunostomy. Abdomen was closed in layers after placing drains.

Figure 2.

Ct angiography image showing replaced right hepatic artery (short arrow) arising from superior mesenteric artery (long arrow).

Figure 3.

Resected specimen showing two ducts viz. Common hepatic duct and right posterior sectoral duct. Arrow pointing to large size open duct is the cut end of common hepatic duct and the arrow showing small size open duct is the cut end of sectoral duct.

Figure 4.

Postoperative MRCP image showing two separate anastomoses of right posterior sectoral duct (long arrow) and common hepatic duct (curved arrow) into the jejunum. MRCP, magnetic resonance cholangiopancreatography.

Outcome and follow-up

Postoperative recovery was uneventful. Feeds were started through feeding jejunostomy tube on postoperative day (POD) 2. Drain to blood amylase ratio was 32:29 on POD 3. On POD 8, pancreaticojejunostomy site drain was removed; subsequently, she was discharged with the drain placed at the site of hepaticojejunostomies as it had high serous fluid in the drain. During the follow-up visit on POD 15, the drain placed at the site of hepaticojejunostomies was removed. Histopathological evaluation revealed IPNB with high-grade dysplasia. There was mixed foveolar and intestinal differentiation (figure 5). It had already spread to the overlying duodenal mucosa. Contrast-enhanced MRI study was performed at 6 months after surgery did not show papillary neoplasms in liver and pancreas. The patient is still under the follow-up.

Figure 5.

Immunohistochemical analysis of markers for IPNB histological subtypes—positive for MUC5A (gastric) and CK-19 (intestinal). IPNB, intraductal papillary neoplasm of bile duct.

Discussion

IPNB is an uncommon condition and has a wide spectrum of clinical presentation and radiological findings.³ Preoperatively, it is usually a diagnostic challenge in view of the variety of presentations. Clinically, it may present with abdominal colic, symptoms suggestive of obstructive jaundice or cholangitis. However, isolated presentation of generalised pruritus as the only presentation of IPNB has not been mentioned in the English literature. Our case had history of prolonged pruritus over a period of 6 months and jaundice that lasted for fortnight in the beginning. Similarly, radiological findings may vary from ductal dilatation which may be mild to severe, diffuse or focal, with or without any intraductal mass, or small lesions such as cast or focal stricture; nonetheless, the most common radiological presentation mentioned in the literature was diffuse duct dilatation with intraductal mass in around half of the cases.^{4 5} Radiological imaging is important to delineate the biliary anatomy. A study observed normal biliary anatomy in only 57.6% of population.⁶ We found a rare variant of biliary anatomy in our patient-A5 (1.6%) in classification given by Huang et al.⁷ Also, we noted variation in origin of right hepatic artery intraoperatively. It was found to be arising from superior mesenteric artery (type 3).⁸

An elevated level of alanine amino transferase is the only test found to differentiate it from conventional cholangiocarcinoma.⁹ Yeh et al analysed CA19-9 to be elevated at a greater frequency in patients with malignant IPNB (61%) as compared with benign (35%).¹⁰ Similarly, carcinoembryonic antigen (CEA) was found to be raised in around 25% of patients with malignant IPNB.¹⁰ In our case, we found elevation of CA 19-9 while CEA was not tested and it turned out to be a low grade dysplasia without invasion.

A proper preoperative evaluation would include ultrasonography to look for bile duct dilatation and differentiate from choledocholithiasis. Endoscopic ultrasonography is a good modality to evaluate the depth of invasion and lymph node involvement.^{11 12} CECT and contrast-enhanced MRI may also help to detect tumours larger than 1 cm and proximal or distal bile duct dilatation. Contrast enhancement is less likely to be persistent and these lesions usually present with washout of enhancement. Magnetic resonance cholangiopancreatography may further elucidate the extent of tumour, its multifocality and narrowing of the bile ducts.^{13 14} However, endoscopic or transhepatic cholangiography or per oral cholangioscopy remain superior as they are able to demonstrate mucin overproduction and identify additional lesions.^{15 16} Cholangioscopy is recommended to evaluate the extent of lesion and tailor the resection which may be done preoperatively or intraoperatively.¹⁶

The main modality of treatment for those without distant metastasis remains surgical resection. Intraoperative frozen sections can further help in tailoring the resection. If only intrahepatic ducts are involved, hepatectomy may suffice. Extrahepatic and extrapancreatic duct involvement may need complete resection from formation of CBD and intrapancreatic portion. Positive proximal or distal frozen section may require addition of partial liver or pancreatic resection.¹⁷ However, some even advocate a complete removal of biliary tree by liver transplantation and pancreaticoduodenectomy.^{18 19} In our case, we did complete removal of extra hepatic biliary tree and pancreaticoduodenectomy.

Kim et al reported difference in clinical features and prognosis in different histological types.⁴ Histopathology report suggested a mixed pancreaticobiliary and foveolar pattern of growth in our case. While intestinal variant is the most common, oncocytic histological subtype is uncommon in Asian population.⁴ Pancreaticobiliary type being the most aggressive while gastric the least. However, mixed subtype is not mentioned in the English literature. Survival and prognosis of these patients depends on histological subtype, differentiation, extent of resection (R0 vs R1), presence and depth of invasive component and lymphovascular invasion. In view of pancreaticobiliary subtype with high-grade dysplasia this case warrants a close follow-up. In our case, a contrast-enhanced MRI study was done at 6 months follow-up period. The scan did not show any lesion (papillary neoplasms) in the liver and pancreas. Furthermore, this patient would undergo a close follow-up with clinical examination and ultrasonography 6 monthly, and MRI studies involving abdomen with MR cholangiopancreatography annually.

Learning points.

• Intraductal papillary neoplasm of bile duct (IPNB) is very uncommon condition and has a wide spectrum of clinical, radiological and pathological presentations.

• IPNB with its variable findings poses a diagnostic challenge and is confirmed by histopathological evaluation.

• Pancreaticobiliary anomalies are a rule and not an exception; surgeon should have knowledge and skills to prevent inadvertent injury to vital structures.

• Regular follow-up of the case is required as IPNBs are known to present as second primary in remaining ducts in liver and pancreas.

• Prognosis of IPNB depends on histological subtype, resected margin, depth of invasion and lymph node status.