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Intraductal papillary neoplasm of the bile duct with invasive carcinoma—A case report


1 Department of Pathology, King Khalid University, Abha, KSA
2 Department of Laboratory Medicine, Aseer Central Hospital, Abha, KSA

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Date of Submission07-Aug-2021
Date of Decision16-Sep-2021
Date of Acceptance20-Nov-2021
Date of Web Publication26-May-2022
 


How to cite this URL:
Fatima S, M. Badri RN. Intraductal papillary neoplasm of the bile duct with invasive carcinoma—A case report. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jan 29]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345897




Dear Editor,

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare bile duct epithelial tumor accounting for 4% to 15% of bile duct tumors. IPNB is mainly found in patients in Far Eastern areas, such as Taiwan, Japan, and Korea, where hepatolithiasis and clonorchiasis are endemic.[1] It is included in World Health Organization classification, 2010 as precursor of intrahepatic (IH) cholangiocarcinoma and is characterized by dilated IH bile ducts filled with a noninvasive papillary or villous biliary neoplasm covering delicate fibrovascular stalks.[2] It is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.[1] We present a 22 years old female with abdominal pain and loss of appetite which on histopathology proved to be IPNB with invasive carcinoma.

A 22-year-old female patient presented with right-sided abdominal pain off and on, loss of appetite for a month. Alanine aminotransferase (ALT)-232 (Normal 0-41 U/L), aspartate aminotransferase (AST)-143 (Normal 0-37 U/L), but all other investigations were within normal range. Computerized tomography (CT) abdomen revealed an 8.4 × 7.2 × 9.0 cm lesion occupying the left liver lobe. The liver had preserved texture with no evidence of nodularity and patent portal vein. Gall bladder, common bile duct, pancreas, spleen, both kidneys were grossly unremarkable. No enlarged mesenteric lymph nodes, free fluid, or free air are seen. No evidence of lytic lesion is seen in lumbar spine [[Figure 1]: a1]. Chest CT: was unremarkable. Magnetic resonance imaging (MRI) of the abdomen revealed average-sized liver with left liver lobe showing large well-defined lesion measuring 8.7 × 8.5 × 7 cm with peripheral nodular infiltrations [[Figure 1]: a2]. Left hepatic lobe hepatectomy was done. Gross examination of left hepatectomy specimen measured 17 × 13 × 10 cm and cut section showed fragile tumor measuring 11 × 11 × 6.5 cm having brownish nodular surface. Histopathology revealed papillary neoplasm covering delicate fibrovascular stalks with areas of invasion [Figure 1]b, [Figure 1]c, [Figure 1]d. Histological grade: well-to-moderately differentiated tumor confined to hepatic parenchyma with IH vascular invasion was noted. Surgical resection margins were free of tumor, pT2 NXMX. Immunohistochemistry revealed cytokeratin (CK) 19, epithelial cell adhesion molecule (EPCAM) and CK7 positivity [Figure 2]a, [Figure 2]b, [Figure 2]c and CK20, hepatocyte paraffin-1 (Hep Par-1) [Figure 2]d, paired box gene-8 (PAX-8), and estrogen receptor (ER) negativity. It was diagnosed as IPNB with associated invasive carcinoma grade 2.
Figure 1: a1. Computed tomography (CT) showing 8.4 × 7.2 × 9.0 cm lesion occupying the left liver lobe. a2. Magnetic resonance imaging (MRI) showing large well-defined lesion showing peripheral nodular infiltrations in left liver lobe. b. Section of liver showing large papillary tumor filling the intrahepatic bile ducts (black arrow) and hepatic parenchyma (blue arrow). c. The cyst is lined by epithelium thrown into papillary processes. d. Section of liver showing an area of invasive adenocarcinoma into the liver parenchyma, tubular type. (Hematoxylin and eosin: b × 10×, c × 20×, d × 40×)

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Figure 2: a. Immunohistochemical study a. Showing cytokeratin (CK) 7 positivity in neoplastic cells (CK7 × 40×) b. Showing CK19 positivity in neoplastic cells CK19 × 20×) c. Showing EPCAM (epithelial cell adhesion molecule) positivity in neoplastic cells (EPCAM × 20×) d. Showing Hep par-1 negativity in neoplastic cells (Hep par-1 × 20×)

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IPNB is an epithelial tumor with intraductal papillary proliferation. The prevalence of IPNBs among biliary neoplasms was found to be 4%.[3] It was recognized as a distinct biliary tract disease by the World Health Organization in 2010 where it was included in precursor and early lesions category of IH cholangiocarcinoma[2] prior to which they were grouped as biliary papilloma and papillomatosis.

The most common clinical manifestations of patients with IPNB are right hypochondrial pain, repeated episodes of acute cholangitis, and obstructive jaundice. Anemia and loss of body weight are relatively less common.[1] Our patient presented with abdominal pain and loss of appetite.

They have similarities with intraductal papillary mucinous neoplasm (IPMN) of the pancreas and can be regarded as a spectrum of biliary diseases with pancreatic counterparts.[4] Both are papillary and intraductal, showing similar range of differentiation of the neoplastic cells, and having similar types of associated invasive carcinomas.[2] They can be divided into two categories: type 1—similar to prototypes of IPMN and type 2—different from prototypes of IPMN. Type 1 IPNB typically develops in the IH bile ducts, while type 2 IPNB has a more complex histological architecture with irregular papillary branching or with foci of solid-tubular components and typically involves the extrahepatic (EH) bile ducts.[4]

Radiologically, papillary bile duct neoplasms could be correctly classified into either IPNBs or papillary cholangiocarcinoma (PCCs) by their cystic appearance, frond-like mural nodule, downstream bile duct dilatation, less extensive upstream bile duct dilatation, and absence of abnormal duct wall enhancement adjacent to the nodule in IPNB and location (PCCs in distal bile duct).[3]

Macroscopically, IH-IPNBs are more likely to show unilocular or multilocular cystic dilatation of the affected ducts where papillary neoplasms are identifiable, while EH-IPNBs are typically associated with cylindrical or fusiform dilatation of the affected bile ducts. IPNB in our case was IH and multilocular. Excessive mucin hypersecretion is almost always found in IPMN and frequently found in IH-IPNB but is uncommon in IPNBs in the EH bile duct.[4] Microscopically they are of three subtypes: intraductal papillary neoplasm with: low- or intermediate-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and with associated invasive carcinoma.[2] Our patient was diagnosed as IPNB with associated invasive carcinoma grade 2. IPNBs are histologically classifiable into four subtypes based on the lining epithelial cells and architectures, including fibrovascular stroma: intestinal, gastric, pancreatobiliary (PB), and oncocytic.[4]

Immunohistochemical study shows that IPNBs express CK7, CK20, and mucin (MUC) 5AC, which are markers of biliary, intestinal, and gastric epithelium, respectively. PB type is the most common type of IPNB. As in the pancreas, when associated with an invasive carcinoma, the PB type of IPNB is usually associated with a tubular adenocarcinoma, while the intestinal type of IPNB is usually associated with a colloid type of invasive carcinoma.[2] MUC1 expression is frequently associated with the development of invasive lesions, especially tubular adenocarcinoma, while mucinous carcinoma is usually associated with negativity for MUC1 but positivity for MUC2. Overexpression of enhancer of zeste homolog 2 might be associated with malignant behavior in IPNB, in parallel with upregulated MUC1 expression and downregulated MUC6 expression.[5]

The differentials of IPNB are conventional nodular/sclerosing cholangiocarcinomas, metastatic carcinomas, particularly those from colorectal adenocarcinoma, biliary intraepithelial neoplasms, intraductal tubulo-papillary neoplasms of the bile duct.

In conclusion, IPNBs are rare tumors which resemble IPMN with no characteristic radiological findings, many histopathological differentials and difficult histopathological subtyping as invasion can be ascertained with multiple careful sectioning. It has better prognosis as compared to cholangiocarcinomas and less invasive surgical approach is the treatment of choice.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Wan XS, Xu YY, Qian JY, Yang XB, Wang AQ, He L, et al. Intraductal papillary neoplasm of the bile duct. World J Gastroenterol 2013;19:8595-604.  Back to cited text no. 1
    
2.
Nakanuma Y, Curado MP, Franceschi S, Gores G, Paradis, Sripa V, et al. Intrahepatic cholangiocarcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: International Agency for Research on Cancer; 2010.  Back to cited text no. 2
    
3.
Komori T, Inoue D, Zen Y, Yoneda N, Kitao A, Kozaka K, et al. CT imaging comparison between intraductal papillary neoplasms of the bile duct and papillary cholangiocarcinomas. Eur Radiol 2019;29:3132-40.  Back to cited text no. 3
    
4.
Nakanuma Y, Kakuda Y, Uesaka K. Characterization of intraductal papillary neoplasm of the bile duct with respect to the histopathologic similarities to pancreatic intraductal papillary mucinous neoplasm. Gut Liver 2019;13:617-27.  Back to cited text no. 4
    
5.
Sasaki M, Matsubara T, Yoneda N, Nomoto K, Tsuneyama K, Sato Y, et al. Overexpression of enhancer of zeste homolog 2 and MUC1 may be related to malignant behaviour in intraductal papillary neoplasm of the bile duct. Histopathology 2013;62:446-57.  Back to cited text no. 5
    

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Correspondence Address:
Sohaila Fatima,
Department of Pathology, King Khalid University, Abha
KSA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_799_21



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