Mucosa-associated lymphoid tissue (MALT) lymphoma as an unusual cause of malignant hilar biliary stricture: a case report with literature review
© The Author(s). 2016
Received: 18 March 2016
Accepted: 22 June 2016
Published: 24 June 2016
Biliary strictures at the hilum of the liver arise from heterogeneous etiologies. The majority is malignant entities, but some may have benign etiologies. It is difficult to distinguish between malignant and benign biliary strictures preoperatively. It has been reported that 5~15 % of preoperative diagnoses of hilar cholangiocarcinoma turn out to be benign lesions or even other types of malignancies. Primary non-Hodgkin’s lymphoma of the extrahepatic bile duct is very rare, with only a few cases reported as mucosa-associated lymphoid tissue (MALT) lymphoma arising from the hepatic duct bifurcation. We herein report a case of a female patient presenting with perihilar bile ducts obstructed by primary MALT lymphoma resembling hilar cholangiocarcinoma, along with a review of the literature.
An 86-year-old female was referred to our hospital manifesting obstructive jaundice and abdominal pain. The reported imaging studies revealed distended intrahepatic bile duct with the stricture of common hepatic duct including bifurcation, which was suspicious of cholangiocarcinoma of the bile duct. The initial laboratory-confirmed cholestasis with a total bilirubin of 8.6 mg/dL, aspartate amino transferase (AST) 178 U/L, alanine transferase (ALT) 105 U/L, and the tumor marker CA 19-9 was elevated with a value of 167 U/mL. Viral markers for hepatitis B and C viruses were negative. She underwent extrahepatic bile duct resection and hepaticojejunostomy. Histological examination of the resected specimen revealed MALT lymphoma. Postoperative follow-up of 1 year has been completely uneventful, without any symptoms or disease recurrence.
In exceptional cases, in which radiologic and clinical features point to cholangiocarcinoma, the actual reason for obstructive jaundice and abdominal pain can be a non-Hodgkin’s lymphoma. In the case of a MALT lymphoma, it can be cured with complete resection.
KeywordsB cell lymphoma Hilar cholangiocarcinoma Klatskin tumor Magnetic resonance cholangio-pancreatography
Space-occupying lesions at any level of the biliary tree impede bile flow and present as diffuse or focal dilatation of upstream bile ducts on radiographic studies. In correlation with clinical and biochemical features, intrahepatic bile ducts with diameters exceeding 40 % of that of adjacent portal veins and extrahepatic bile ducts with diameters greater than 7 mm on ultrasound and 10 mm on computed tomography (CT) both imply a narrowing of the bile duct. As such, further evaluation of presumed biliary stricture is required to determine location and extent. The majority of biliary strictures are malignant, but up to 30 % may arise from benign etiologies . There is no precise method of preoperatively distinguishing malignant from benign biliary strictures, which means that up to 20 % of patients undergoing surgical resection for suspected biliary malignancies actually have a benign disease [2, 3].
Hilar cholangiocarcinoma, also known as Klatskin tumor, is a malignant tumor that narrows the confluence of the left and right hepatic ducts. Only 20–30 % of patients are potentially curable with surgical resection, a major operation with a less than promising oncologic outcome . As such, some physicians are trying to avoid the surgical option, as it may actually worsen the clinical condition. Histopathological studies reveal 5–15 % of these to be benign lesions or other malignancies that are curable by complete resection .
Primary low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a subtype of non-Hodgkin’s lymphoma. Thirty-four cases of primary non-Hodgkin’s lymphoma of the extrahepatic bile duct have been reported, while only four cases of MALT lymphoma arising from the hepatic duct bifurcation have. We elaborate here on the case of an 86-year-old female patient, who presented with perihilar bile duct obstruction by primary MALT lymphoma resembling hilar cholangiocarcinoma.
An extranodal marginal zone B cell lymphoma, also called low-grade B cell lymphoma of MALT, arises in a number of epithelial tissues, including the stomach, salivary gland, lung, small intestine, and thyroid. It has a tendency to remain localized to the tissue of origin over time, but does recur frequently, with potential for systemic spread and transformation to a high-grade B cell lymphoma. The pathogenesis of MALT lymphoma owes to chronic inflammation of the tissue, which leads to the local accumulation and proliferation of antigen-dependent B cells and T cells. With time, B cell clones emerge, still dependent on antigens for growth and survival. At the stage of monoclonal proliferation, these cells are not able to spread beyond the site of inflammation. With acquisition of additional mutations, however, the tumor becomes antigen-independent and capable of systemic spread . This patient had no known history of prior cholangitis or any evidence of hepatitis, so it is hard to be suspicious of any chronic antigenic stimulation which carries etiologic specificity. The underlying etiologic mechanism of bile duct involvement by this type of lymphoma should be further elucidated.
Summary of cases of primary mucosa-associated lymphoid tissue lymphoma resembling Klatskin tumor
Shimura et al. 
Irregular, incomplete stenosis from hilum to the lower part of the bile duct
Mass (4.5 × 3.5 cm) around the EHD
Right trisegmentectomy + caudate lobectomy
Shito et al. 
Dilatation of IHD with a circumscribed heterogeneous mass in the main hepatic junction
Dense, white, nodular mass (5.0 × 2.5 cm) in the main hepatic junction
Left hemihepatectomy + caudate lobectomy + radical bile duct resection + Roux-en-Y hepaticojejunostomy + chemotherapy (CHOP, 3 cycles)
Yoon et al. 
Dilatation of IHD with long, segmental, circumferential wall thickening of entire extrapancreatic portion of CBD + cystic duct + right posterior, anterior segmental IHD + left secondary biliary confluence
Diffuse wall thickening of EHD with smooth inner and outer surface without mass lesion
Right hemihepatectomy + caudate lobectomy + radical bile duct resection + Roux-en-Y hepaticojejunostomy + chemotherapy (CVP, 6 cycles)
MiKail et al. 
Dilatation of IHD with a mass at liver hilus with intrahepatic biliary dilatation
4 cycles of R-CHOP (rituximab/cyclophosphamide/doxorubicine/vincristine/prednisolone)
Diffuse dilatation of IHD and wall thickening of CHD
Intraluminal mass in the proximal CBD and on the duodenal side, a spreading tumor-like lesion
Radical bile duct resection + Roux-en-Y hepaticojejunostomy
The three patients who had undergone surgery were males aged 59 to 71 years (mean 64 years). They had been admitted to the hospital for jaundice with mean total and direct bilirubin levels of 11.15 and 7.85 mg/dL. Radiological studies revealed that the perihilar bile ducts were diffusely thickened, with irregular, incomplete stenosis or long circumferential wall thickening shaped. All patients who underwent surgery had received a preoperative diagnosis of Klatskin tumor. On postoperative immunohistochemical studies, however, bile duct narrowing turned out instead to be related to MALT lymphoma. In three cases, partial hepatectomy combined with caudate lobectomy were also performed. In our case, a negative resection margin was secured without the need for further hepatic resection, as the proximal margin was preserved just below perihilar duct bifurcation.
To avoid misdiagnosing and inappropriately treating cases of MALT lymphoma resembling Klatskin tumor, several suggestions have been made. According to Shimura et al., evaluation of incomplete stenosis of the bile duct by 18-F fluoro-2-deoxyglucose positron emission tomography can distinguish MALT lymphoma from Klatskin tumor . Yoon et al. propose that it is necessary to consider MALT lymphoma when cholangiography shows smooth luminal narrowing of the extrahepatic bile duct without mucosal irregularity, despite diffuse thickening of the ductal wall on CT and magnetic resonance imaging (MRI) . Still, it remains difficult to diagnose primary MALT lymphoma in this region on either CT or MRI. MiKail et al. reported a unique case that was diagnosed without the need for surgical specimens : a 58-year-old female patient was thought to have a Klatskin tumor and was prepared for major surgery; however, a type of lymphoma was suspected based on concerning biological behavior of the tumor (rapid growth resulting in doubling of size within a month), and the patient underwent a tru-cut biopsy via percutaneous transhepatic cholangiography (PTC), which led to the diagnosis of low-grade B cell lymphoma at the hepatic hilum without the need for surgery.
At the time of diagnosis, only 20–30 % of patients with Klatskin tumors are operable, leaving the remainder to follow a course of palliative treatment . Biliary stents in both the right and left hepatic ducts help relieve jaundice and minimize the risk of cholangitis. With complications of stents, such as occlusion and migration, stent patency lasts only a few months before replacement becomes necessary. However, palliative stenting is actually inappropriate for patients diagnosed with primary MALT lymphoma mimicking Klatskin tumor. Whereas patients with inoperable Klatskin tumors can expect less than 1 year of survival, non-gastric MALT lymphomas have an indolent course, resulting in a 5-year survival rate of 93 % . For the latter, chemotherapy or resection of space-occupying lesions can improve patient quality of life and long-term survival.
The greatest number of patients with extrahepatic bile duct cancer lies within the 75–84 year age range at diagnosis . Patients 70 years or older are referred to as the elderly, and advanced age has been considered to be a contraindication for surgery, out of fear that extended resection of hepatobiliary tumors is too risky. In addition, life expectancy for the elderly is usually underestimated . In one study, 14 % of inoperable Klatskin tumors were due to advanced age and coexisting medical conditions . The 86-year-old female patient in our case had previously been considered inoperable due to her advanced age but was in fact well on the way to the recovery after surgery. There has been a recent trend to change this preconception and allow elderly patients more opportunities to undergo surgery. Resection of hepatobiliary cancer can be offered to the elderly as well as to patients with few co-morbidities and good functional status . A study of Veterans Administration (VA) patients aged 80 years and over showed that the 30-day mortality rate was better predicted by functional status than by chronological age . If preoperative performance status is favorable, a forward-looking approach to major biliary surgery in elderly patients can provide them a chance for cure.
Although primary MALT lymphoma in the perihilar bile duct is very rare, strong clinical suspicion can lead to an accurate preoperative diagnosis and subsequent cure by surgical resection, chemotherapy, or both.
CBD, common bile duct; CT, computed tomography; MALT, mucosa-associated lymphoid tissue; MRI, magnetic resonance imaging
We would like to acknowledge the patient and her family for allowing us to use her medical records in our case report and allowing this case to be published.
Specific funding was not used to perform this study.
Availability of data and materials
We respect the patient’s rights to privacy and to protect his identity, so we do not wish to share our patient data. We presented, in the manuscript, all the necessary information about case report. Raw data regarding our patient is in her admission file, a file that is strictly confidential, without the possibility of publishing raw data from it.
YKP, JEC, and CWC designed the case report. YKP, JEC, and WYJ wrote the manuscript. SKS, JIL, and CWC reviewed the manuscript. All authors discussed the case and commented on the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient and her son for publication of this case report and any accompanying images.
This clinical study of the abovementioned case report was waived by the institutional review board at our center.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Tummala P, Munigala S, Eloubeidi MA, Agarwal B. Patients with obstructive jaundice and biliary stricture +/− mass lesion on imaging: prevalence of malignancy and potential role of EUS-FNA. J Clin Gastroenterol. 2013;47:532–7.View ArticlePubMedGoogle Scholar
- Clayton RA, Clarke DL, Currie EJ, Madhavan KK, Parks RW, Garden OJ. Incidence of benign pathology in patients undergoing hepatic resection for suspected malignancy. Surgeon. 2003;1:32–8.View ArticlePubMedGoogle Scholar
- Gerhards MF, Vos P, van Gulik TM, Rauws EA, Bosma A, Gouma DJ. Incidence of benign lesions in patients resected for suspicious hilar obstruction. Br J Surg. 2001;88:48–51.View ArticlePubMedGoogle Scholar
- Ito F, Cho CS, Rikkers LF, Weber SM. Hilar cholangiocarcinoma: current management. Ann Surg. 2009;250:210–8.View ArticlePubMedGoogle Scholar
- Senthil Kumar MP, Marudanayagam R. Klatskin-like lesions. HPB Surg. 2012;2012:107519.View ArticlePubMedPubMed CentralGoogle Scholar
- Isaacson PG. Mucosa-associated lymphoid tissue lymphoma. Semin Hematol. 1999;36:139–47.PubMedGoogle Scholar
- Shimura T, Kuwano H, Kashiwabara K, Kojima M, Masuda N, Suzuki H, et al. Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. Hepatogastroenterology. 2005;52:360–2.PubMedGoogle Scholar
- Yoon MA, Lee JM, Kim SH, Lee JY, Han JK, Choi BI, et al. Primary biliary lymphoma mimicking cholangiocarcinoma: a characteristic feature of discrepant CT and direct cholangiography findings. J Korean Med Sci. 2009;24:956–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Shito M, Kakefuda T, Omori T, Ishii S, Sugiura H. Primary non-Hodgkin’s lymphoma of the main hepatic duct junction. J Hepatobiliary Pancreat Surg. 2008;15:440–3.View ArticlePubMedGoogle Scholar
- Mikail C, Sefa T, Tamer K, Anil SO, Gulcin Y. Primary extrahepatic bile duct lymphoma mimicking Klatskin’s tumor, dramatic response to chemotherapy. Int J Surg Case Rep. 2015;8c:147–9.View ArticlePubMedGoogle Scholar
- Goenka MK, Goenka U. Palliation: hilar cholangiocarcinoma. World J Hepatol. 2014;6:559–69.PubMedPubMed CentralGoogle Scholar
- Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT lymphomas. Hematology Am Soc Hematol Educ Program 2001:241–258Google Scholar
- SEER Cancer Statistics Review 2008–2012. http://seer.cancer.gov.
- Petrowsky H, Clavien PA. Should we deny surgery for malignant hepato-pancreatico-biliary tumors to elderly patients? World J Surg. 2005;29:1093–100.View ArticlePubMedGoogle Scholar
- Burke EC, Jarnagin WR, Hochwald SN, Pisters PW, Fong Y, Blumgart LH. Hilar cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system. Ann Surg. 1998;228:385–94.View ArticlePubMedPubMed CentralGoogle Scholar
- di Sebastiano P, Festa L, Buchler MW, di Mola FF. Surgical aspects in management of hepato-pancreatico-biliary tumours in the elderly. Best Pract Res Clin Gastroenterol. 2009;23:919–23.View ArticlePubMedGoogle Scholar
- Hamel MB, Henderson WG, Khuri SF, Daley J. Surgical outcomes for patients aged 80 and older: morbidity and mortality from major noncardiac surgery. J Am Geriatr Soc. 2005;53:424–9.View ArticlePubMedGoogle Scholar