Primary hepatic mucosa-associated lymphoid tissue lymphoma: a case report and literature review
- Shigeyuki Nagata1Email author,
- Norifumi Harimoto1 and
- Kiyoshi Kajiyama1
Received: 27 February 2015
Accepted: 17 September 2015
Published: 24 September 2015
Abstract
Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease. We herein describe the findings in a 74-year-old man with elevated liver enzyme levels. Dynamic computed tomography showed focal biliary dilation and atrophy in the posterior segment, while dynamic magnetic resonance images revealed a small, highly enhanced small mass located at the root of posterior branch of the biliary ducts. As the mass was not detected on abdominal ultrasonography, a biopsy could not be performed. Cholangiocellular carcinoma was suspected, and surgery was performed. However, the surgically resected hepatic tumor was a nodule of aggregated lymphocytes that formed a lymphoepithelial lesion. Immunohistochemical analysis revealed that the lymphoma cells were positive for CD20 and CD79a, but negative for CD3. No other lymphoid lesions were found during additional postoperative examinations. Therefore, the patient was diagnosed with primary hepatic MALT lymphoma. He was also diagnosed with Helicobacter pylori infection, and thus, pylorus eradication was performed. At the time of this report, the patient was free of disease for 2 years without any additional treatment. The present case contributed to the diagnosis and management of this rare disease, as previously published case reports described varying imaging features; it also suggested that preoperative diagnosis was often difficult without biopsy.
Keywords
Background
Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade malignant lymphoma that was first described by Isaacson and Wright in 1983 [1]. The stomach is one of the most common sites of MALT lymphoma development, and gastric MALT lymphoma is commonly associated with Helicobacter pylori (HP) infection. However, primary hepatic lymphoma (PHL) is very rare, accounting for approximately only 0.016 % of all cases of all non-Hodgkin’s lymphoma cases [2]. Furthermore, primary hepatic MALT lymphoma is extremely rare among the diagnosed PHL cases. In addition, the standard diagnostic method and treatment strategy of this disease have yet to be established. Herein, we describe a case of surgically resected primary hepatic MALT lymphoma, which was initially suspected to be a cholangiocellular carcinoma, and review the relevant literature.
Case presentation
A 74-year-old man was referred to our department for mild elevation of liver enzyme levels. He had no significant medical history except for hypertension that was medically managed. His family history was unremarkable. Physical examination at presentation did not indicate any abnormalities. The laboratory tests conducted at our hospital showed the following findings: hemoglobin level of 17.4 g/dl, a platelet count of 204,000/μl, albumin level of 4.5 g/dl, total bilirubin level of 0.6 mg/dl, aspartate aminotransferase level of 22 IU/L, alanine aminotransferase level of 34 IU/L, lactate dehydrogenase level of 160 IU/L, γ-glutamyltranspeptidase level of 36 IU/L, alkaline phosphatase level of 338 IU/L, C-reactive protein level of 0.43 mg/dl, IgG level of 2199 mg/dl, and IgM level of 268.7 mg/dl. Hepatitis B surface antigen and anti-hepatitis C virus antibody in the serum were negative. Anti-nuclear antibody and anti-mitochondrial antibody were also negative. Tumor marker levels including carcinoembryonic antigen, carbohydrate antigen 19-9, α-fetoprotein, and des-γ-carboxy prothrombin were within the normal ranges.
Computed tomography findings. a Dynamic computed tomography with drip infusion cholangiography revealed focal dilatation of the biliary ducts (arrow) and atrophy (arrowheads) in the posterior segments of the liver. b No tumor was detected via enhanced computed tomography
Enhanced magnetic resonance imaging after gadolinium injection. The tumor was hyper-intense on T1-weighted images (arrow) in the area adjacent to the main posterior biliary duct in the arterial phase but showed rapid washout in the late phase
Tumor characteristics. a Grossly, the 7-mm white mass along the posterior biliary duct was soft and non-encapsulated. b Histological findings on hematoxylin and eosin staining. The lesion consisted of dense lymphocyte infiltration with some lymph follicles. c and d Small to mid-sized lymphocytes formed lymphoepithelial lesions on some bile capillaries
Histological findings by immunohistochemical staining. Lymphocytes were diffusely positive for CD20 and CD79a antibodies
Subsequently, the patient’s level of interleukin-2 receptor was found to be elevated at 1133 U/ml (normal range, 122–496 U/ml). He was also infected with HP and medical treatment for pylorus eradication was provided. Biopsy of the bone marrow revealed a normoplastic marrow. Positron emission tomography demonstrated diffuse accumulation in both the thyroid glands, with a maximum standardized uptake value of 4.0. Biopsy of the thyroid glands showed chronic thyroiditis without malignancy, and the patient’s thyroid function was within normal limits. The present case of MALT lymphoma was diagnosed a stage I tumor, according to the Ann Arbor classification, and careful follow-up without additional treatment was selected. At the time of this report, the patient remained alive and free of disease 2 years after surgery.
Discussion
MALT lymphoma often develops at several anatomic sites, including the gastrointestinal tract, lungs, head and neck, skin, thyroid glands, breasts, and liver. Gastric MALT lymphoma is thought to be triggered by chronic inflammation, which can occur in different diseases including chronic gastritis associated with HP infection, Sjogren syndrome, and Hashimoto thyroiditis [3]. The etiology of primary hepatic MALT lymphoma is unclear, but it has been reported that primary biliary cirrhosis [4–8], hepatitis C viral infection [8–13], hepatitis B viral infection [14–16], ascariasis [17, 18], and HP infection [19] are possibly related with the pathogenesis of hepatic MALT lymphoma.
At presentation, our patient was not infected with hepatitis viruses, and his thyroid function and bone marrow were normal. He was also negative for anti-nuclear and anti-mitochondrial antibodies. However, his serum IgG and IgM levels were elevated, and he showed HP infection. Such clinical findings suggested that the hepatic MALT lymphoma might be strongly associated with chronic inflammation caused by HP infection. Subsequent treatment for HP infection after surgery was successful.
Reported cases of hepatic MALT lymphoma
Case | Sex/age | HBV | HCV | Concomitant disease | Tumor no. | Treatment | Outcome |
|---|---|---|---|---|---|---|---|
1 | M/66 | ND | ND | Ureteral cancer | 1 | Resection | 12 M/alive |
2 | F/73 | ND | ND | (−) | 1 | Resection | Lost to follow-up |
3 | M/85 | ND | ND | Prostatic cancer | 2 | (−) | Death after other surgery |
4 | F/60 | ND | ND | Liver cirrhosis | Multiple | Transplantation | 12 M/dead |
5 | F/57 | (−) | ND | Ascariasis | 1 | Resection | 55 M/alive |
6 | M/48 | (+) | ND | Hepatitis | 1 | Resection + Chemotherapy | 38 M/alive |
7 | F/47 | (−) | (−) | Multiple biliary unilocular cysts | 1 | Resection + Radiation | 30 M/alive |
8 | M/64 | (−) | (−) | Colon cancer | 1 | Resection | Lost to follow-up |
9 | F/62 | (−) | (−) | Primary biliary cirrhosis | 1 | Resection | 6 M/alive |
10 | F/64 | (−) | (+) | Liver cirrhosis | 1 | Chemotherapy | 24 M/alive |
11 | F/65 | (−) | (+) | Hepatitis | 1 | Chemotherapy | 48 M/alive |
12 | F/69 | (−) | (−) | (−) | 1 | Resection | Short time/alive |
13 | F/41 | (−) | (−) | Primary biliary cirrhosis | 1 | (−) | 12 M/alive |
14 | F/64 | (−) | (−) | (−) | 1 | Resection | 72 M/alive |
15 | F/57 | (−) | (−) | Primary biliary cirrhosis | 1 | Transplantation | 9 M/alive |
16 | F/64 | (−) | (−) | Ascariasis | 1 | Resection | Pulmonary recurrence after 96 M |
17 | F/59 | ND | ND | ND | Multiple | Resection + Chemotherapy | ND |
18 | M/61 | (−) | (−) | Gastric cancer | 1 | Resection | 18 M/alive |
19 | M/73 | (−) | (+) | Liver cirrhosis | 1 | Resection | 34 M/alive |
20 | M/59 | (−) | (+) | Hepatitis | 1 | Resection | 30 M/alive |
21 | F/50 | (−) | (−) | (−) | 1 | Resection + Chemotherapy | 30 M/alive |
22 | F/72 | ND | ND | Colon cancer | 1 | (−) | 1 M/dead |
23 | F/61 | ND | ND | Rheumatoid arthritis | 1 | (−) | Dead |
24 | F/58 | ND | ND | (−) | Multiple | Resection + Chemotherapy | 37 M/alive |
25 | F/62 | ND | ND | Breast cancer | 1 | Resection | 9 M/alive |
26 | F/65 | (+) | (−) | Hepatocellular carcinoma | 1 | Resection | 10 M/alive |
27 | F/60 | (−) | (−) | Gastric MALT lymphoma | 1 | (−) | 30 M/alive |
28 | M/59 | (+) | (−) | Liver cirrhosis | 2 | Transplantation | 6 M/Alive |
29 | M/36 | (+) | (−) | Hepatitis | 1 | Resection | Hepatic recurrence after 40 M |
30 | M/53 | (−) | (+) | Liver cirrhosis | Multiple | Transplantation + Chemo | ND |
31 | M/67 | (−) | (−) | Hepatitis (drug) | 1 | Radiation | Pulmonary recurrence after 72 M |
32 | M/69 | (−) | (−) | (−) | 2 | RFA + Chemo | 24 M/alive |
33 | F/74 | (−) | (−) | (−) | 1 | Resection + Chemotherapy | 6 M/alive |
34 | F/67 | NA | NA | Gastric MALT lymphoma | Multiple | (−) | 1 M/dead |
35 | F/72 | (−) | (−) | Colon cancer | 1 | Resection | 24 M/alive |
36 | M/64 | (−) | (−) | Gastric cancer | Multiple | (−) | 24 M/alive |
37 | M/71 | (−) | (−) | (−) | 1 | Resection | 15 M/alive |
38 | M/71 | (−) | (−) | (−) | 1 | Resection + Chemotherapy | 45 M/alive |
39 | F/56 | (−) | (−) | (−) | 1 | Resection | Pulmonary recurrence after 84 M |
40 | M/59 | (−) | (−) | (−) | 1 | Resection | 5 M/alive |
41 | M/86 | (+) | (−) | Hepatitis | 1 | (−) | 15 M/alive |
42 | M/58 | (−) | (+) | Hepatitis | 1 | Resection + Chemotherapy | 6 M/alive |
43 | F/43 | (−) | (−) | Gastric cancer | 1 | Resection | 24 M/alive |
44 | F/80 | (−) | (−) | Primary biliary cirrhosis | Multiple | Chemotherapy | ND |
45 | M/76 | (−) | (+) | Hepatitis | 1 | Radiation | 60 M/alive |
46 | F/74 | (−) | (−) | Colon cancer | 2 | Resection | 24 M/alive |
47 | F/74 | (−) | (−) | Primary biliary cirrhosis | Multiple | Chemotherapy | 36 M/alive, no relapse |
48 | M/73 | (−) | (+) | Hepatitis | Multiple | Chemotherapy | 24 M/alive, relapse |
49 | F/56 | (−) | (−) | (−) | 1 | Resection | 13 M/alive |
50 | M/77 | (−) | (+) | Hepatitis | 1 | Resection | 8 M/alive |
Our case | M/74 | (−) | (−) | (−) | 1 | Resection | 30 M/alive |
According to the abovementioned case reports, primary hepatic MALT lymphoma tends to be solitary and small. Furthermore, it is often difficult to make a definite diagnosis of primary hepatic MALT lymphoma solely based on the imaging findings as the disease seem to exhibit variable imaging features. Therefore, it is necessary to accumulate more cases and establish a therapeutic strategy for primary hepatic MALT lymphoma.
Conclusions
In the present report, we described a case of primary hepatic MALT lymphoma. Our experience in this case and review of relevant literature indicated that preoperative diagnosis of hepatic MALT lymphoma might be challenging because of the disease’s varying imaging features. Thus, further study of this extremely rare disease is necessary.
Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
Abbreviations
- CT:
-
computed tomography
- HP:
-
Helicobacter pylori
- MALT:
-
mucosa-associated lymphoid tissue
- MRI:
-
magnetic resonance imaging
- PHL:
-
primary hepatic lymphoma
- US:
-
ultrasonography
Declarations
Acknowledgements
We would like to thank Editage (www.editage.jp) for English language editing.
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.
Authors’ Affiliations
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