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ANALYTICAL REPORT
Year : 2012  |  Volume : 8  |  Issue : 1  |  Page : 114-116

Complete response to chemotherapy in primary hepatic lymphoma


1 Department of Hematotology, Sir Ganga Ram Hospital, New Delhi, India
2 Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
3 Department of Histopathology, Sir Ganga Ram Hospital, New Delhi, India

Date of Web Publication19-Apr-2012

Correspondence Address:
Mir Sadaqat Hassan Zafar
Department of Hematology, Room No. 3, First Floor, SSRB, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.95187

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 > Abstract 

Primary hepatic lymphoma is an uncommon lymphoid tumor with varied clinical presentations and treatment outcomes. The median age of involvement is 50 years (male preponderance) with median survival as 8-16 months. Here we report a 68-years-old female who presented with right hypochondriac pain and anorexia with hepatomegaly on physical examination. Ultrasonography (USG) with subsequent contrast enhanced computed tomography (CECT) of abdomen depicted a hypoechoic mass in the left lobe of liver. CECT of chest and neck showed no abnormality. Liver biopsy proved to be Non-Hodgkin lymphoma (NHL) diffuse large B cell type, CD20 positive. Bone marrow examination showed no infiltration by NHL. The patient was started on three weekly R-CHOP, given a total of 8 cycles. Patient attained a complete remission documented by negative computed tomography (CT) and positron emission tomography (PET) scans.

Keywords: Chemotherapy, diagnosis, primary hepatic lymphoma


How to cite this article:
Zafar MH, Aggarwal S, Bhalla S. Complete response to chemotherapy in primary hepatic lymphoma. J Can Res Ther 2012;8:114-6

How to cite this URL:
Zafar MH, Aggarwal S, Bhalla S. Complete response to chemotherapy in primary hepatic lymphoma. J Can Res Ther [serial online] 2012 [cited 2020 Sep 20];8:114-6. Available from: http://www.cancerjournal.net/text.asp?2012/8/1/114/95187


 > Introduction Top


Neoplastic lesions found in the liver with imaging tests are not uncommon since the liver is, after lymph nodes, the most common tissue involved by metastasis. Primary hepatic lymphoma (PHL) is characterized by liver involvement at presentation with no affectation of the spleen, lymph nodes, peripheral blood, bone marrow, or other tissues until at least six months after diagnosis. [1] There is paucity of literature, addressing the best treatment option and post treatment course for PHL. Present case highlights the superiority of combination chemotherapy over the more invasive therapeutic modalities (surgery and radiotherapy).


 > Case Report Top


A 68-years-old female presented with one-month history of pain in the right hypochondriac region of abdomen, mild in intensity and without any radiating features. The patient had loss of appetite of same duration and denied any history of fever, cough, weight loss or altered bowel habits. There was no other significant past medical or surgical history. Clinical examination was remarkable for hepatomegaly of 5 cm below right costal margin and no other abnormality. Liver was non-tender and surface irregular on left side. Baseline ECG, chest-X-ray, complete blood count and kidney function tests were normal. Liver function tests showed mild elevation of enzymes (AST-52 IU/L; ALT-76 IU/L). Viral markers for hepatitis B and C were negative. Lactate dehydrogenase (170U/L), uric acid (5.6 mg/dl) and calcium (9.5mg/dl) were within normal limits. Ultrasonography (USG) of abdomen showed hepatomegaly with the presence of a large hypoechoic area in left lobe of liver. Subsequently contrast enhanced computed tomography (CECT) of abdomen and pelvis was performed that revealed irregular and nodular mass in left lobe of liver measuring at least 17×11 cm. Central, irregular and low attenuation areas were seen within the mass which were persistent in arterial, venous and delayed phases. Few prominent vessels were seen along the outer margin of the mass anteriorly. No other abnormal finding was detected within rest of the abdomen and pelvis [Figure 1]. CECT of chest showed normal lung fields and no mediastinal or paratracheal lymphadenopathy. Serum levels of alpha-fetoprotein (1.26 μg/l) and carcinoma embryonic antigen (0.34 μg/l) were normal. Ultimately diagnostic liver biopsy was performed that revealed sheets and nests of round cells, surrounded by mature lymphoid cells at periphery. On immunohistochemistry, these cells stained positive for LCA, CD20 and negative for CK [Figure 2]. The findings were consistent with NHL diffuse large B cell type. Bone marrow examination showed no infiltration by lymphoma. Final diagnosis in this case was primary hepatic lymphoma, diffuse large B cell type, stage IE because single extranodal site was involved. Patient was started on R-CHOP: Rituximab (375 mg/m 2 ) with cyclophosphamide (750 mg/m 2 ), doxorubicin (50 mg/m 2 ), vincristine (1.2 mg/m 2 ) and prednisolone (40 mg/m 2 ) every 21 days. CECT of abdomen was done after 5 cycles of chemotherapy that showed marked regression of the mass lesion to 6.5×5.5 cm in left lobe of liver [Figure 3]. A total of 8 cycles of chemotherapy were given and PET/CT was done after completion of chemotherapy that showed normal physiological uptake of dye and liver was free of any lesion [Figure 4]. The patient is on our close follow-up since 18 months post chemotherapy and on last visit to our out-patient department, she was symptom free with normal blood chemistry.
Figure 1: CECT of abdomen showing large mass lesion of left hepatic lobe with central low attenuation areas

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Figure 2: Immunohistochemistry showing CD20 + diffuse large B cell type NHL

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Figure 3: CECT of abdomen showing marked regression of left hepatic lesion after 5 cycles of R-CHOP

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Figure 4: Normal PET scan following 8 cycles of R-CHOP

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 > Discussion Top


Secondary involvement of the liver by non-Hodgkin lymphoma is relatively common (21% of advanced cases) whereas primary hepatic lymphoma (PHL) is an extremely rare disorder (<1%). Presentation of PHL varies from an incidental finding of liver function test abnormality in an otherwise asymptomatic individual to the onset of fulminant hepatic failure. The etiology of PHL is still unknown, although vi­ruses such as hepatitis B, hepatitis C, Epstein-Barr and human immunodeficiency have been implicated. [1]

In PHL, the levels of the alpha-fetoprotein (AFP) and carcinoma embryonic antigen (CEA) are normal. Radiological findings remain nonspecific and lesions are positive on fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET). Liver biopsy is the main tool for diagnosing PHL. The predominant histology is diffuse large B-cell lymphoma type (46-68%). Other histologic subtypes described in literature include lymphoblastic and Burkitt lymphoma (17%), follicular lymphoma (4%), diffuse histiocytic lymphoma (5%), lymphoma of MALT type, anaplastic large cell lymphoma, T-cell rich B-cell lymphoma and mantle cell lymphoma. [2]

There is no proper guideline for the treatment of PHL. Available options include surgery, chemotherapy, radiation or varying combinations of these modalities. It has been suggested that, for low-volume localized PHL, surgical resection, alone or in combination with chemotherapy, might be a treatment option. But, as relapse after surgery is not unusual and PHL is chemosensitive, combination chemotherapy should be always employed. Matano et al, reported a patient of PHL who underwent surgical resection following which relapse occurred. Subsequently patient responded to CHOP and attained remission, demonstrating the usefulness of combination chemotherapy. [3]

Avlonitis produced data of 72 patients of PHL who were treated with different modalities and showed median survival of 14 months when chemotherapy (n=40) alone was used, 20.7 months for surgery plus chemotherapy (n=14), 29 months for surgery alone (n=8) and 12.5 months for chemotherapy plus radiotherapy (n=8). [4] Page et al reviewed a series of 24 patients and documented that outcome of patients with PHL who are treated with combination chemotherapy may be more favorable than that reported elsewhere. [5] Navarro et al also reported a patient of PHL with complete response to R-CHOP who remained symptom free for more than two years. [6]

R-CHOP protocol increased the complete-response rate and prolonged the survival significantly. De Renzo et al, analyzed six patients of PHL, out of which four were DLBCL type, one MALT (mucosa associated lymphoid tissue lymphoma) and one PTCL (peripheral T-cell lymphoma). Five patients received CHOP and one patient received R-CHOP (DLBCL). All patients were in remission. [7] Quintyne et al, demonstrated complete response to R-CHOP in a patient of PHL, diffuse large B cell type. [8] Yang et al, in their retrospective analysis of nine PHL patients pointed to its prognostic variability and good response to early surgery combined with postoperative chemotherapy in strictly selected patients. [9]

Currently, patients with chemo-refractory DLBCL of liver have relatively limited therapeutic options. Neither autologous nor allogeneic SCT offer notable benefit in this setting. Novel agents like yttrium-90 ibritumomab tiuxetan and iodine-125 tositumomab have shown some promise in patients with chemorefractory DLBCL. [10]

In conclusion, PHL needs a high index of suspicion for its diagnoses. It is a treatable malignancy of liver if detected early. Current literature favors the combination chemotherapy as the frontline treatment for its least invasiveness and improved survival. However, more data are needed from prospective, controlled studies to assess the role of combination chemotherapy as a single modality of therapy.

 
 > References Top

1.Salmon JS, Thompson MA, Arildsen RC, Greer JP. Non-Hodgkin's lymphoma involving the liver: Clinical and therapeutic considerations. Clin Lymphoma Myeloma 2006;6:273-80.  Back to cited text no. 1
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2.Gomyo H, Kagami Y, Kato H, Kawase T, Ohshiro A, Oyama T, et al. Primary Hepatic Follicular Lymphoma: A case report and discussion of chemotherapy and Favourable Outcomes. J Clin Exp Hematop 2007;47:73-77.   Back to cited text no. 2
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3.Matano S, Nakamura S, Annen Y, Hattori N, Kiyohara K, Kakuta K, et al. Primary hepatic lymphoma in a patient with chronic hepatitis B. Am J Gastroenterol 1998;93:2301-2.  Back to cited text no. 3
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4.Avlonitis VS, Linos D. Primary hepatic lymphoma: A review. Eur J Surg 1999;165:725-29.  Back to cited text no. 4
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5.Page RD, Romaquera JE, Osborne B, Medeiros LJ, Rodriquez J, North L, et al. Primary Hepatic Lymphoma: Favourable outcome after combination chemotherapy. Cancer 2001;92:2023-29.  Back to cited text no. 5
    
6.Serrano-Navarro I, Rodriquez-López JF, Navas-Espejo R, Perez-Jacoiste MA, Martinez-González MA, Grande C, et al. Primary hepatic lymphoma - favorable outcome with chemotherapy plus rituximab. Rev Esp Enferm Dig 2008;100:724-28.  Back to cited text no. 6
    
7.De Renzo A, Perna F, Persico M, Notaro R, Mainolfi C, de Sio I, et al. Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin's lymphoma. Eur J Haematol 2008;81:51-57.  Back to cited text no. 7
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8.Quintyne KI, Geoghegan J, Nolan N, Lawlor L, Guptal RK. Extra-nodal lymphoma-a case of primary hepatic lymphoma: Favourable outcome following multiagent chemotherapy. Cancer Ther 2009;7:449-53.  Back to cited text no. 8
    
9.Yang XW, Tan WF, Yu WL, Shi S, Wang Y, Zhang YL, et al. Diagnosis and surgical treatment of primary hepatic lymphoma. World J Gastroenterol 2010;16:6016-19.  Back to cited text no. 9
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10.Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, et al. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood 2007;110:54-8.  Back to cited text no. 10
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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