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Hepat Mon. 2011;11(3):203-205
Primary hepatic diffuse large B cell lymphoma: A case report
Yuan-Ji Ma 1, En-Qiang Chen 1, Xue-Bing Chen 1, Juan Wang 1, Hong Tang 1*
1 Center of Infectious Diseases, West China Hospital of Sichuan University, Sichuan Province, China
c 2011 Kowsar M.P.Co. All rights reserved.
* Corresponding author at: Hong Tang, Center of Infectious Diseases, West China
Hospital of Sichuan University, Chengdu, People's Republic of China. Tel: +86-
A B S T R A C T
In this report we describe a rare case of primary hepatic diffuse large B cell lymphoma in a
67-year-old man who presented with abdominal pain, deteriorated liver function, elevated
lactate dehydrogenase. He was found to have diffuse nodular intrahepatic space-occupying
lesion with normal α-fetoprotein and carcino-embryogenic antigen. The final diagnosis was
made by percutaneous biopsy of the liver as the clinical manifestation not consistent with
common liver diseases. The patient was treated with R-CHOP (rituximab, cyclophosphamide,
doxorubicin, vincristine and prednisone) without surgical resection with a favorable re-
sponse. However, serious complication was occurred after 4 cycles of chemotherapy, and the
patient finally died of concurrent acute respiratory distress syndrome.
A R T I C L E I N F O
Received: 01 Aug 2010
Revised: 06 Sep 2010
Accepted: 13 Oct 2010
Primary hepatic lymphoma
Diffuse large B cell lymphoma
c 2011 Kowsar M.P.Co. All rights reserved.
Primary hepatic lymphoma (PHL) is an unusual form of
non-Hodgkin's lymphoma that usually presents with consti-
tutional symptoms, hepatomegaly and signs of cholestatic
jaundice without lymph node and extrahepatic (.i.e., the
spleen, bone marrow and other lymphoid tissue) lymphoma
proliferation at early stage of the disease (1). The prevalence of
PHL was 0.4% among extranodal non-Hodgkin's lymphoma,
and 0.016% among all non-Hodgkin's lymphoma (2). Because
of its rarity, non-specific clinical symptoms, laboratory and
imaging performance, PHL was often misdiagnosed as hepa-
titis, primary liver cancer or metastatic tumor. In this case
report, we present a patient with pathologically confirmed
primary hepatic diffuse large B cell lymphoma.
A 67-year-old Chinese man was hospitalized for fatigue, an-
Implication for health policy/practice/research/medical education:
Gastoentroloigsts and hepatologists should know about one of the very rare causes of liver tumors and consider this cause in differential
diagnosis of other similar disorders.
Please cite this paper as:
Ma YJ, Chen EQ, Chen XB, Wang J, Tang H. Primary hepatic diffuse large B cell lymphoma: A case report. Hepat Mon. 2011;11(3):203-205.
orexia, yellowish discoloration of skin and sclera, and right
upper quadrant abdominal pain. The patient had no com-
plaints of fever, significant weight loss. He did not have his-
tory of smoking, alcohol consumption and drugs abuse. He
had a history of cholecystectomy at the age of 45. Physical
examination revealed no abnormal findings except for ten-
derness on percussion on liver and edema in both lower ex-
tremities. There was no palpable superficial lymphadenopa-
thy. He had no hepatosplenomegaly. Laboratory findings
showed deteriorated liver function, elevated blood lipids
and lactate dehydrogenase (LDH) (Table 1). Serologic tests for
hepatitis A, B and C were negative; serum α-fetoprotein (AFP)
and carcinoembryonic antigen (CEA) levels were normal.
Immunoglobulin levels were normal without any monoclo-
nal peak in the plasma or urine electrophoresis. Abdominal
ultrasound and computed tomography (CT) revealed diffuse
occupying nodules in liver (Figure 1A). Subsequent magnetic
resonance imaging (MRI) revealed diffuse lesions that were
hypointense on T1 and hyperintense on T2-weighted im-
ages (Figure 1B). There was no evidence of biliary or pancre-
atic disease, splenomegaly or abdominal lymphadenopathy.
Bone marrow biopsy demonstrated normal proliferation
and maturation of all cell lines. There was no malignant
Hepat Mon. 2011;11(3):203-205
204 Ma YJ et al.
Primary hepatic diffuse large B cell lymphoma
infiltration; flowcytometry examination also showed no ob-
vious abnormality of bone marrow. A core liver biopsy was
performed, showing heavy infiltration composed mainly of
medium-sized round cells (Figure 2A). The cells were posi-
tive for CD20 and LCA (Figures 2B and 2C), and proliferation
index was very high with ki67 positive in 90% of cells (Fig-
ure 2D), establishing a diagnosis of diffuse large B-cell lym-
phoma, according to the WHO classification. After discuss-
ing treatment options and the risks of chemotherapy with
the patient and her family, the patient was then received at-
tenuated chemotherapy (R-CHOP: rituximab 500 mg, cyclo-
phosphamide 400 mg, doxorubicin 40 mg, vincristine 2 mg,
and prednisone 60 mg). The courses of chemotherapy were
given every 2–3 weeks. After receiving two more cycles of the
chemotherapy (rituximab 500 mg, cyclophosphamide 800
mg, doxorubicin 60 mg, vincristine 2 mg and prednisone 60
mg), his liver function was improved—the level of LDH was
decreased (Table 1), and the intrahepatic diffuse tuberculous
lesions were decreased both in number and size. However,
after the 4th cycle of the chemotherapy, the patient devel-
oped neutropenia, diarrhea, followed by intestinal bleeding,
signs of peritonitis, and pneumonia. Unfortunately, his con-
dition got worse rapidly, and the patient finally died of con-
current acute respiratory distress syndrome (ARDS).
Table 1. Laboratory test results
a Laboratory results before the first chemotherapy
b Laboratory results before the second chemotherapy
c Laboratory results before the third chemotherapy
Weeks after the first admission
Reference Values Unit
117.7 286.8 356.8115.020.4 2.0-28.0µmol/L
97.1 232.4 278.593.0 15.0< 8.8 µmol/L
79 93 1095714< 55 U/L
139 24329154 32< 46 U/L
467 1025 1492 435127 47-138U/L
637595 827 342 1176-46 U/L
32.5 26.123.6 30.9 34.5 35-55g/L
36.438.6 39.730.2 20.319-34 g/L
1.89 2.843.16 3.191.880.29-1.83 mmol/L
6.13 11.0614.2210.103.07 2.8-5.7 mmol/L
434513448 197211 110-220 U/L
Figure 2. Histological and immunohistochemical photographs of liver tumor.
(A): Hematoxylin and eosinstaining, 400×; (B): anti-CD20 staining, 400×; (C): anti-
LCA staining, 400×; (D): anti-ki67 staining, 400×
Figure 1. Abdominal computed tomography (A) and T1-weighted magnetic resonance imaging (B), revealing multiple occupying nodules in liver. Neither splenomegaly
nor abdominal lymphadenopathy was observed.
Hepat Mon. 2011;11(3):203-205 Download full-text
Primary hepatic diffuse large B cell lymphoma
Ma YJ et al.
Non-Hodgkin’s lymphoma is a common malignant dis-
ease. Liver involvement occurs in 10% of patients and is a sign
of advanced disease. PHL refers to an extra-nodal lymphoma
of the liver without involvement of any other organ (e.g.,
lymph node, spleen, etc) (3, 4). The vast majority (67%) of PHL
patients are middle-aged men who usually present with ab-
dominal pain, nausea and constitutional symptoms (4). PHL
is notably rare, representing <1% of all extra-nodal lympho-
ma (4). One Chinese study reported that in 446 cases of non-
Hodgkin’s lymphoma, 45 developed liver involvement, of
which only one had PHL (5). Limited experience showed that
PHL had non-specific clinical manifestations. Hepatomegaly
is found in most patients, constitutional symptoms (e.g.,
fever, night sweats and weight loss) appear in 37%, fever in
86%, weight loss in 57% and jaundice in 4% (3, 6). In liver, PHL
may present as a solitary mass (42%) or as multiple lesions
(50%). Patients with PHL have abnormal liver function tests
(cholestasis and cytolysis) (7, 8), mostly elevated LDH and al-
kaline phosphatase (ALP) (6, 9). Additionally, hypercalcemia
is found in 40% of the patients. The cause of PHL is not en-
tirely clear, but may be related to viral hepatitis (10, 11). Hepa-
titis C virus (HCV) infection is found in 20%–60% of patients
with PHL. The frequent association with HCV suggests that
this virus may play a role in the pathogenesis of PHL (7, 8).
PHL is also seen in immunocompromised patients, but the
relationship between PHL occurrence and immune deficien-
cy has not yet been reported. Our patient had neither hepa-
titis C infection nor signs of immunodeficiency. Therefore,
we speculated that PHL also could occur in patients without
any prior liver disease. Diagnosis of PHL requires a liver bi-
opsy compatible with lymphoma and absence of lymphop-
roliferative disease outside the liver. Through analyzing 90
patients with hepatic lymphoma, Lei Ki (4) proposed the fol-
lowing criteria for the diagnosis of primary hepatic lympho-
ma: 1) the symptoms are mainly caused by liver involvement
at presentation; 2) no clear evidence of superficial lymph
node enlargement and distant lymph node metastasis; 3) no
abnormalities in peripheral blood cells in blood smears, in-
cluding spleen, lymph node and bone marrow. Some other
studies also reported that the dynamic change of serum LDH
could be used as a diagnostic marker (12). However, the value
of LDH for the diagnosis of PHL is limited because of its poor
specificity. Therefore, a definite diagnosis of PHL is difficult
to establish solely based on clinical signs and symptoms. The
imaging presentation of PHL is variable and can be a solitary
intrahepatic lesion, multiple nodules and diffuse infiltra-
tion of the liver. In the imaging reports of 12 patients with
PHL provided by Elsayes KM, et al (13), there were three cases
of solitary nodules, one with diffuse damage, and eight with
multiple nodular liver lesions. Multiple nodular lesions in
liver accounted for the majority of these cases, while diffuse
infiltration was rare. Imaging of our patient showed diffuse
nodular lesions, and the presentation varied in ultrasound,
CT or MRI. Therefore, there is no pathognomonic imaging
pattern to confirm the diagnosis.
Hepatoma and metastasis from gastro-intestinal (mostly
colon) carcinoma present very similarly and are much more
common. Normal levels of the tumor markers, AFP and CEA
are found in almost 100% of patients with PHL facilitating
the differential diagnosis (3, 4, 6). The examination of the co-
lon to exclude primary colon carcinoma may be indicated.
Thus, a definite diagnosis of PHL should include histologi-
cal and marker studies of the biopsy sample. Our patient
presented with clinical and laboratory features which were
suggestive for PHL; liver biopsy stained with specific immu-
no-histochemical stains and flowcytometric studies also
confirmed the diagnosis of PHL. There is no consensus on
the optimal treatment for PHL. Surgical treatment, radio-
therapy and chemotherapy were all reported as treatment
modalities alone or in combination. The prognosis of PHL
is considered very poor with a median survival as low as
six months for patients treated with chemotherapy alone.
With the availability of rituximab (a monoclonal chimeric
antibody directed against CD20 B cell antigen), chemother-
apy protocols for the treatment of PHL have dramatically
changed in the last decade. R-CHOP protocol increased the
complete-response rate and prolonged the survival signifi-
cantly. Unfortunately, our patient was died of complications
of chemotherapy. Our report indicated that complications
caused by chemotherapy still would be a major problem.
In conclusion, PHL is a rare disease, lacking specific imag-
ing and clinical manifestations and biochemical indicators.
Its diagnosis is difficult, needing to exclude organs or tis-
sues lymphoma outside of the liver. When multiple space-
occupying lesions are found in liver but there is no any other
organ or tissue invasion, PHL should be suspected and liver
biopsy should be done. If the diagnosis is made, chemother-
apy should be started immediately, and adverse reactions
and complications should be closely monitored.
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