unusual case of plasmablastic non-hodgkin’s lymphoma ... · against hepatitis b and c virus were...

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Unusual case of plasmablastic Non-Hodgkin’s lymphoma located in the liver. First case reported in an AIDS patient Humberto Metta,* Marcelo Corti,* Aldo Maranzana,* Ricardo Schtirbu,* Marina Narbaitz,** Marcela De Dios Soler** * HIV/AIDS Division, Infectious Diseases F. J. Muñiz Hospital. ** National Academy of Medicine, Buenos Aires, Argentina. ABSTRACT Plasmablastic lymphoma is a rare and a relatively new entity that was first described in the jaws and the oral cavity of HIV-AIDS patients. We report a case of plasmablastic lymphoma involving the liver in an AIDS patient. Plasmablastic lymphoma is considered a diffuse large B-cell lymphoma with a unique phenotype and predilection for the oral cavity. The case presented had a unique hepatic lesion, localized in the left lobe of the liver. Diagnosis was confirmed by hepatic biopsy guided by Computerized Tomography scan and histopathology. The smears showed a dense infiltrate composed by atypical lymphocytes with numerous plasmocytes expressing the plasma cell markers MUM-1 and CD138 and negative for the B-cell markers CD3, CD20 and CD45. Immunohistochemical and in situ hibridization revealed the Epstein-Barr virus genome in the atypical cells. Polymerase chain reaction was negative for HHV-8 RNA. Key words. Plasmablastic lymphoma. Liver. HIV. AIDS. Correspondence and reprint request: Humberto Metta Unit 17, Infectious Diseases F. J. Muñiz Hospital Tucumán 1630 3º C, C1050 AAH Buenos Aires, Argentina. E-mail: [email protected] Manuscript received: May 17, 2009 Manuscript accepted: June 21, 2009. July-September, Vol. 8 No.3, 2009: 242-245 CASE REPORT INTRODUCTION Since 1985, lymphoma is an AIDS-defining illness and non-Hodgkin lymphoma (NHL) is the second most common neoplasm behind Kaposi’s sarcoma in these patients. Individuals with AIDS have a 100 to 300 times higher risk to develop a NHL in compari- son with the general population. As well, intrave- nous drugs users have an additional risk among the patients with HIV infection. 1 Plasmablastic lymphoma (PBL) is an aggressive and distinct sub-type of AIDS-related NHL. It is a frequent tumor in the oral cavity but is infrequent in other locations. 2 Here we present the first case of plasmablastic NHL of the liver reported in an AIDS patient. CASE REPORT A 47-year old heterosexual man, infected by HIV was admitted with a 20 days history of nauseas, vo- mit, abdominal pain and weight loss. Physical exa- mination revealed a worsening condition, fever, epi- gastric and upper right quadrant abdominal pain and liver enlargement. Significant laboratory findings included: hemoglo- bin 9.5 g/dL; hematocrit 28%; white cells count 3,300/mm 3 ; platelets 215,000/mm 3 ; alkaline phos- phatase 157 U/L (N = 90 to 240 U/L) and lactate dehydrogenase 409 U/L (N = 230 to 460 U/L). Transaminase and alpha-fetoprotein levels were nor- mal. Serological tests to detect specific antibodies against hepatitis B and C virus were negatives. The CD4 T-cell count was 37 cells/μL (8%) and the plas- ma viral load was over to 500,000 copies/mL. Abdominal ultrasound scan showed a heteroge- neous large mass of 3 cm diameter, located in the left hepatic lobe (Figure 1) with contrast enhance- ment. Bone marrow biopsy was negative to detect atypi- cal cells infiltration. A computerized tomography (CT) scan of thorax, abdomen and pelvis showed he- patomegaly with the same lesion present in ultraso- nographic examination. CT percutaneous-guided fine needle liver biopsy was performed. Histopathological examination of biopsy smears showed a dense infiltrate composed of a diffuse proliferation of large immunoblast cells with the typical morphological appearances of a

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Page 1: Unusual case of plasmablastic Non-Hodgkin’s lymphoma ... · against hepatitis B and C virus were negatives. The CD4 T-cell count was 37 cells/µL (8%) and the plas-ma viral load

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Unusual case of plasmablasticNon-Hodgkin’s lymphoma located in the liver.

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Since 1985, lymphoma is an AIDS-defining illnessand non-Hodgkin lymphoma (NHL) is the secondmost common neoplasm behind Kaposi’s sarcoma inthese patients. Individuals with AIDS have a 100 to300 times higher risk to develop a NHL in compari-son with the general population. As well, intrave-nous drugs users have an additional risk among thepatients with HIV infection.1

Plasmablastic lymphoma (PBL) is an aggressiveand distinct sub-type of AIDS-related NHL. It is afrequent tumor in the oral cavity but is infrequentin other locations.2

Here we present the first case of plasmablasticNHL of the liver reported in an AIDS patient.

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A 47-year old heterosexual man, infected by HIVwas admitted with a 20 days history of nauseas, vo-

mit, abdominal pain and weight loss. Physical exa-mination revealed a worsening condition, fever, epi-gastric and upper right quadrant abdominal painand liver enlargement.

Significant laboratory findings included: hemoglo-bin 9.5 g/dL; hematocrit 28%; white cells count3,300/mm3; platelets 215,000/mm3; alkaline phos-phatase 157 U/L (N = 90 to 240 U/L) and lactatedehydrogenase 409 U/L (N = 230 to 460 U/L).Transaminase and alpha-fetoprotein levels were nor-mal. Serological tests to detect specific antibodiesagainst hepatitis B and C virus were negatives. TheCD4 T-cell count was 37 cells/µL (8%) and the plas-ma viral load was over to 500,000 copies/mL.

Abdominal ultrasound scan showed a heteroge-neous large mass of 3 cm diameter, located in theleft hepatic lobe (Figure 1) with contrast enhance-ment.

Bone marrow biopsy was negative to detect atypi-cal cells infiltration. A computerized tomography(CT) scan of thorax, abdomen and pelvis showed he-patomegaly with the same lesion present in ultraso-nographic examination.

CT percutaneous-guided fine needle liver biopsywas performed. Histopathological examination ofbiopsy smears showed a dense infiltrate composedof a diffuse proliferation of large immunoblast cellswith the typical morphological appearances of a

Page 2: Unusual case of plasmablastic Non-Hodgkin’s lymphoma ... · against hepatitis B and C virus were negatives. The CD4 T-cell count was 37 cells/µL (8%) and the plas-ma viral load

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high-grade NHL. Numerous cells had a plasmablastappearance (Figure 2). Immunostaining with mono-clonal antibodies (DAKO - Glostrup, Denmark)showed atypical cells, negative for standard B-cellmarkers CD3, CD20 but expressing CD45, MUM-1(Figure 3), CD138 and other markers of plasma celldifferentiation. Bcl-6 was negative and the Ki-67(proliferative) index was high (> 95% of the tumorcells) (Figure 4). Definitive histopathological diag-nosis was high grade plasmablastic NHL.

Epstein-Barr virus (EBV) associated latent mem-brane protein-1 (LMP-1) was detected in tumor cellsby immunohistochemichal (IHQ) while EBV-encodedmRNAs was revealed by in situ hybridization (ISH)(Figure 5). Real-time polymerase chain reaction (RT-PCR) was negative to detect the HHV-8 RNA in theneoplastic cells.

Patient died three months after the diagnosis,despite one cycle of standard CHOP chemotherapy

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Page 3: Unusual case of plasmablastic Non-Hodgkin’s lymphoma ... · against hepatitis B and C virus were negatives. The CD4 T-cell count was 37 cells/µL (8%) and the plas-ma viral load

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was carried on. The patient’s physical conditiondid not allow him to receive other cycles of chemo-therapy.

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The plasmablastic variant of diffuse large B celllymphoma (DLBCL) is now considered to be a hete-rogeneous group of rare tumors, occurring especia-lly in the context of HIV infection (PBL of the oralcavity).3,4

PBL was originally described in 1997 as a uniquelesion in the oral cavity of an HIV seropositive malepatient.5 Subsequently, it has been described inother sites as the skin, the stomach, the lung andthe rectum, including HIV seronegative patients. InHIV-infected subjects this neoplasm occurs in up to3% of the patients.6-9

PBL is a CD20 negative and a MUM-1, CD38 and/or CD138 and VS38c positive large B cell lymphomaand the clinical course was aggressive and rapidlyfatal without treatment.10 The World Health Orga-nization (WHO) classification of lymphomas of the2000 year includes PBL as a variant of DLBCL.11

Liver involvement is common in disseminatedNHL, but less than 1% of extranodal lymphomascompromise the liver.12 Hepatic involvement in NHL,either primary or secondary, includes diffuse paren-chymal infiltration or single/ multiple liver masses.13

Patients with AIDS related primary liver NHL ge-nerally present “B” symptoms (fever, night sweatsand weight loss), abdominal pain and hepatomegaly,with or without jaundice at the time of diagnosis.

High grade, unfavorable histology and bulky tu-mor volume are associated with poor prognosis, asin our patient. Several series estimated a mediansurvival time of only six months, including those pa-tients who received chemotherapy.14

Ultrasonographic and computerized tomographyscans might be helpful for the diagnosis of focal he-patic lesions in AIDS patients, but no imaging fin-dings are specific for hepatic lymphoma.15 Ourpatient presented a single large and hypoechoic le-sion with contrast enhancement in the sonographicimages (Figure 1).

Image-guided needle fine biopsy of the liver is thebest method for the definitive diagnosis of hepaticlymphoma, as we could observe in our patient.16

Several studies suggested that HCV plays a roleon the pathogenesis of hepatic lymphoma and hepa-tocarcinoma. EBV is also strongly associated to thepathogenesis of NHL in AIDS patients.17 EBV geno-me is present in 35% to 50% of AIDS related NHL.

We could demonstrate the presence of EBV genomein the atypical cells by two techniques, IHQ and ISH(Figure 5).18,19

The Medline, Embase and Cochrane databaseswere searched to identify articles of PBL of the liverassociated with AIDS. The search was performedusing the following key words: plasmablastic lym-phoma, liver, HIV, AIDS. To the best of ourknowledge, PBL of the liver in a patient with AIDShas not been previously reported in the medical lite-rature.

Liver lymphoma should be included in the diffe-rential diagnosis of single hypoechoic lesions in theultrasonographic images in AIDS patients. PBL mayoccur in extra-oral sites in HIV seropositive pa-tients, involving other organs as the liver, andshould be considerer a poor prognosis malignancy.

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