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ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 563-567
 

Plasmablastic lymphoma in HIV patients: Experience at a tertiary care hospital in eastern India


1 Department of Medicine, Medical College, Kolkata, West Bengal, India
2 Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
3 Department of Medicine, Calcutta National Medical College, Kolkata, West Bengal, India
4 Department of Medical Oncology, Medical College, Kolkata, West Bengal, India
5 Department of Pathology, Medical College, Kolkata, West Bengal, India

Date of Web Publication10-Mar-2016

Correspondence Address:
S Bishnu
Department of Medicine, Medical College, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.178437

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 » Abstract 

BACKGROUND: Plasmablastic lymphoma (PBL), a rare non-Hodgkin's lymphoma (NHL) variant specifically associated with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), expresses well-differentiated plasma cell markers like CD138, bright CD38, and MUM1; but not conventional B-cell markers. It occurs at unusual sites like oral cavity and orbit, and has poor survival rates. AIMS: This study serves as a review of a clinical experience with six HIV patients with PBL and observes the spectrum of clinical presentations, histopathologies, and 1-year outcomes in PBL patients. MATERIALS AND METHODS: This review of six PBL patients was conducted at a tertiary care hospital in eastern India using relevant radiological, histopathogical, and immunohistological studies. RESULTS: Incidence of PBL among HIV patients was 0.58% (6/1,028). Mean CD4 count at presentation was 125.5 ± 71.1 cells/μL. Sites of involvement included pleura, lung parenchyma, suprarenal gland, pelvic cavity, and retroorbital space (one each). Immunohistopathology of biopsied sample in each patient revealed PBL (positive plasma cell markers MUM-1/IRF4, CD38, and CD138/syndecan; and negative of B-cell markers CD3, CD20, and CD30). Three (60%) were positive for Epstein Barr virus (EBV) immunoglobulin G (IgG). Five surviving patients received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen and attained partial remission (PR) after six cycles. Subsequently, three patients were started on EPOCH (etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy; two attained near total regression after 6 months (four cycles). Overall, four patients remained alive with good quality of life at the end of 1 year of follow-up. CONCLUSION: PBL in HIV occurs at unusual sites with varying aggressivity. This study is too small to comment on the long-term outcomes of PBL in HIV; however, coadministration of antiretroviral therapy (ART) with standard chemotherapy may improve survival.


Keywords: Adrenal, chemotherapy, human immunodeficiency virus/acquired immunodeficiency syndrome, non-Hodgkin's lymphoma, plasmablastic lymphoma


How to cite this article:
Bishnu S, Banerjee S, Bandyopadhyay D, Samui S, Bhattacharya S, Bose D. Plasmablastic lymphoma in HIV patients: Experience at a tertiary care hospital in eastern India. Indian J Cancer 2015;52:563-7

How to cite this URL:
Bishnu S, Banerjee S, Bandyopadhyay D, Samui S, Bhattacharya S, Bose D. Plasmablastic lymphoma in HIV patients: Experience at a tertiary care hospital in eastern India. Indian J Cancer [serial online] 2015 [cited 2019 Dec 14];52:563-7. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/563/178437





 » Introduction Top


High grade non-Hodgkin's lymphoma (NHL), Kaposi's sarcoma, and invasive cervical cancer are the AIDS defining cancers in HIV infected populations. Plasmablastic lymphoma (PBL) is a rare NHL variant specifically associated with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).[1],[2] PBL expresses well-differentiated plasma cell markers like CD138, bright CD38, and MUM1; instead of conventional B-cell markers like CD20, CD3, S100, and HMB45.[3] PBL is reported to have a predilection for unusual sites like oral cavity, orbit, and esophagus and has poor survival rates.[4] This study was conducted at a large tertiary care hospital in eastern India to identify PBL cases from the large number of HIV patients attending the hospital, to observe the spectrum of clinical presentations and tumor histopathologies in these patients and record 1-year follow-up outcomes in them.


 » Materials and Methods Top


This study is a retrospective review of our clinical experience with 1,028 HIV patients presenting to the institutional HIV/AIDS Referral Center over an 18 month period from June 2010 to November 2011, at a teaching hospital of eastern India. Among these HIV infected patients, 31 were diagnosed as having Hodgkin's or non-Hodgkin's lymphoma and out of them, six patients were diagnosed to have PBL. All of them were admitted to the Department of Medicine, where they underwent clinical examinations and relevant investigations, including radiological and histopathological examinations. The various imaging modalities were undertaken and analyzed by the same radiologist; similarly, the histopathogical and immunohistological slides were reviewed by the same oncopathologist, before a diagnosis of PBL was ascertained. The patients were subsequently treated at the Departments of Medicine and Oncology of the study institution, where they received chemotherapy (sequential CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and EPOCH (etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen) and supportive treatment in accordance with standard guidelines, and reviewed regularly on follow-up up to 12 months from initiation of therapy.[5],[6] The clinical presentations, histological and immunohistochemical findings, CD4 counts, antiretroviral therapy (ART) status and 1-year outcomes were observed and recorded for the purpose of this study. Response to chemotherapy (complete response (CR) and partial response (PR)) was defined in accordance with the guidelines laid down by the National Cancer Institute, Bethesda sponsored International Working Group in 1999.[7] The patients included in this study were sequentially referred to as P1, P2, P3, P4, P5, and P6 for maintaining anonymity. Informed consent was obtained from each of them for conducting guided tissue samplings as well as for inclusion of their medical records in this study. Institutional ethical clearance was also obtained for conducting this study.


 » Results Top


The incidence of PBL among HIV patients was 0.58% (6/1028) in our study. The average age of the six patients was 50.8 ± 3.8 years, all of whom were male. All of them were known to be HIV positive at the time of diagnosis of PBL; the average duration of seropositive status being 25.3 ± 15.7 months (range 3.5–46 months). Mean CD4 count at presentation was 125.5 ± 71.1 cells/µL. Five of the patients were on highly active antiretroviral therapy (HAART; mean duration 26.2 ± 13.6 months), while one patient who had been diagnosed to have HIV infection 13 weeks earlier had refused antiretroviral therapy [Table 1].
Table 1: Demographic and immunological characteristics of study population (n=6)

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The most common symptom at presentation was fever (4/6, 66.7%). The other presenting complaints pertained to the site of local involvement with the lymphoreticular malignancy [Table 2]. Biopsy samples were obtained from sites of clinical involvement: Lymph node, pleural mass, lung mass, suprarenal mass, pelvic mass, and paravertebral mass (one each).
Table 2: Clinical presentation and site of neoplastic involvement (n=6)

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Each patient is described in brief with regards to clinical and radiological findings:

  • P1: A 47-year-old male patient presented with fever, shortness of breath, and right-sided chest heaviness of 3 months duration. He had pallor, mediastinal lymphadenopathy, and a right-sided pleural based mass from which a computed tomography (CT)-guided biopsy was obtained
  • P2: A 46-year-old male had progressively decreasing urine output over 1 week, developed altered sensorium, anuria, and rising serum creatinine following admission. A large pelvic mass was palpated and CT scan of abdomen suggested complete obstruction of both ureters, leading to bilateral hydronephrosis and obstructive renal failure [Figure 1]. A guided biopsy of the pelvic mass was obtained, followed by bilateral ureteral stenting for relief of obstruction. The patient succumbed to renal failure in spite of stenting and hemodialysis, and the biopsy findings were obtained post mortem
  • P3: A 53-year-old male with generalized lymphadenopathy developed sudden onset double vision and a rapidly progressive painful proptosis in the right eye. CT scan of his brain and orbit revealed a right retroorbital mass causing proptosis of the right eye and compressing the right optic nerve. He refused consent for a guided fine needle aspiration from the retroorbital mass. An excision biopsy was performed from his cervical lymph node
  • P4: A 55-year-old alcoholic male suffering from pain abdomen, fever, and weight loss was found to have a large (10 × 8 cm) suprarenal mass on CT scan of abdomen, which was compressing the liver as well as encasing the great vessels [Figure 2]. A guided trucut biopsy was obtained from the suprarenal mass
  • P5: A 50-year-old male smoker presented with fever, pallor, and lymphadenopathy was diagnosed to have a solid mass in the lower lobe of the left lung, ipsilaterlal moderate pleural effusion, and mediastinal lymphadenopathy
  • P6: A 54-year-old patient with poor compliance to ART presented with fever for 4 months and a spastic paraplegia slowly progressing over 2 weeks, along with bowel and bladder involvement. Magnetic resonance imaging (MRI) spine revealed a soft tissue paravertebral mass in lower thoracic region causing compressive myelopathy, from which a CT-guided trucut biopsy was performed.


All the biopsy specimens yielded a histopathogical picture of sheets of monomorphic large lymphoid cells with prominent nucleoli, scant to moderate deeply basophilic cytoplasm, and frequent mitotic figures; suggestive of diffuse large B-cell lymphoma [Figure 3]. Immunohistochemical studies revealed that the lymphoma cells in all biopsy samples phenotypically expressed the plasma cell markers MUM-1/IRF4, CD38, and CD138/syndecan and were negative for B-cell markers (CD3, CD20, CD30, CD79A, ALK-1, BCL-6, and PAX-5). Among the other cell markers, CD56, CD10, CD4, and Bcl-2 were positive in four (66.7%), four (66.7%), two (33.3), and one (16.7%) patients, respectively. Serological testing for presence of Epstein Barr virus (EBV) was performed in all except Patient 2; of these five, three (60%) demonstrated the presence of immunoglobulin G (IgG) antibodies to Epstein Barr viral capsid antigen [Table 3].
Figure 1: Computed tomography (CT) scan of abdomen showing irregular mass lesion of plasmablastic lymphoma (asterisk) in pelvic cavity causing compression of ureters (right ureter depicted by arrow)

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Figure 2: Plasmablastic lymphoma (asterisk) shown to completely replace right-sided suprarenal gland on CT scan of abdomen

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Figure 3: Histopathology of biopsy from adrenal mass showing sheets of monomorphic large lymphoid cells with prominent nucleoli, scant to moderate deeply basophilic cytoplasm, and frequent mitotic figures (×40)

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Table 3: Immunohistochemical and EBV IgG status

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We lost one patient before the tissue diagnosis of PBL could be obtained. The five surviving patients were instituted with chemotherapy for lymphoma (CHOP regimen) under the Department of Medical Oncology. All of them attained partial remission (PR) after six cycles. Subsequently, three out of five patients were started on infusional EPOCH therapy, out of whom two patients attained near total regression after 6 months (four cycles), while one patient succumbed to chemotherapy related complications (febrile neutropenia and severe sepsis). The two patients who opted to remain on conventional CHOP therapy were having stable disease at the completion of 6 monthly cycles of chemotherapy. All these four patients remained alive with good quality of life at the end of 1 year of follow-up [Table 4].
Table 4: Response to therapy at the end of 6 months and 1 year

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 » Discussion Top


Lymphomas occurring specifically in HIV-positive patients include primary effusion lymphoma (PEL) and PBL.[1] Of these, PBL occurs most commonly in young HIV infected adult males, the most common site of occurrence being the oral cavity.[3] Jorge Castillo and colleagues have reported in a recent article that oral involvement in PBL may be as high as 27%.[8] Other rarer sites like orbit and esophagus have also been reported in various case reports.[9],[10] Orbital involvement includes extraocular muscles, optic nerve, as well as retinal and uveal layers. Interestingly, all six patients included in this study had involvement at sites other than the oral cavity.

In our case series, the average age of presentation of the all male patient cohort was 50.8 ± 3.8 years, which was higher when compared to the average age of 38 years reported in the largest study on PBL done till date.[3] In our patients, PBL was found to have nodal as well as atypical extranodal distribution in the form of orbital, adrenal, pleuropulmonary as well as paraspinal involvement. This represents a significant deviation from earlier publications where the eye, oral cavity, and gastrointestinal tract were the principle organ/organ system to be involved.[3],[9],[10] Castillo et al., have opined that the 100% oral cavity involvement seen in earlier studies are not seen in the newer series, probably owing to the wider prevalence of HAART usage amongst HIV infected patients today.[8],[11] Extensive literature search did not lead us to any previous report of obstructive uropathy or adrenal involvement with PBL, as was demonstrated in patients P2 and P4 in our study, respectively [Table 2].

A distinguishing feature of PBL is a poor expression for B-cell markers like CD20, CD3, S100, HMB45, and cytokeratins and a strong reactivity for well-differentiated plasma cells markers, such as CD138 and CD38.[3] In our experience, all the biopsy specimens expressed plasma cell markers MUM-1/IRF4, CD38, and CD138/syndecan. The B-cell markers (CD3, CD20, CD30, CD79A, ALK-1, BCL-6, and PAX-5) were conspicuous by their absence. Indeed, it was this immunohistochemical peculiarity which led us to confirm the diagnosis of PBL in our patients. There was variable expression of the other cell surface markers like CD56, CD10, CD4, and Bcl-2. The EBV coinfection rate stood at 60% in consonance with two earlier studies (52, and 64%, respectively) [Table 3].[3],[12]

HIV associated non-Hodgkin's lymphoma has been known to be an aggressive tumor class, especially PBL, which has reported mortality rates of 53–60% and median survival of 6–15 months.[3],[4] Available literature regarding treatment of PBL in HIV suggests that combining anticancer treatment with antiretroviral drugs may offer the best outcome in terms of better chemotherapy tolerance, an improved complete response rate, a significant improvement of disease-free survival (DFS) and a significant decrease in the number of deaths due to HIV related complications.[1],[13],[14] Till the recent publication of a recent draft guideline for management of HIV associated lymphomas, clinicians have had to rely on large case series data and clinician experiences to decide on chemotherapy regimens for PBL.[10] In a large review on PBL mentioned earlier, the authors reported that a majority of the patients who had CR had received CHOP regimen, while Little and colleagues report that CR rates were as high as 74% in a cohort of 39 HIV positive patients with aggressive lymphomas.[3],[15] In our center too, the choice of CHOP and EPOCH regimen of chemotherapy for PBL was based on the review of literature available during the course of this study.

Our experience in treatment of PBL showed a PR rate of 100.00% at 6 months of CHOP regimen, a near total remission rate of 66.67% with infusional EPOCH regimen and an overall mortality of 33.3%. This compares with recent data published by Castillo and coworkers where CR rate was 67% (all chemotherapy regimens considered). Our patients were followed-up for 1 year from diagnosis and the small number of patients in our study cohort meant that we could not compare between the relative efficacies and benefits of the two chemotherapy regimens, perform survival analysis, or determine prognostic factors for survival. We are inclined to believe that the concomitant use of HAART in all our patients, along with chemotherapy, has positively influenced the clinical outcome of our study.


 » Conclusions Top


We conclude from this study that PBL is not rare among HIV-related cancers and often occur at unusual sites with varying degrees of clinical aggression. The diagnosis must be suspected in HIV patients with low CD4 counts and appropriate immunohistochemistry requested. While we are not eligible to comment on the long-term outcomes of PBL in HIV from this study, we feel confident to suggest that the use of effective ART successfully augments life expectancy when coadministered with standard chemotherapeutic regimens.


 » Acknowledgement Top


The authors wish to acknowledge their gratitude to Dr. Anup Sadhu, Radiologist, EKO CT and MRI Centre, Medical College, Kolkata, for his assistance in performing relevant CT scans and CT-guided biopsies.

 
 » References Top

1.
Carbone A, Cesarman E, Spina M, Gloghini A, Schulz TF. HIV-associated lymphomas and gamma-herpesviruses. Blood 2009;113:1213-24.  Back to cited text no. 1
    
2.
Khairidzan MK, Normalina M, Ismail MA, Siraj H, NorAzlin IM, Zainol R, et al. Atypical ocular presentation of non-hodgkin lymphoma-A case report. Int Med J [Internet]. 2006;5:[ about 1p. ]. Available from: http://www.eimjm.com/Vol5-No1/Vol5-No1-C3.htm [Last cited on 2012].  Back to cited text no. 2
    
3.
Castillo J, Pantanowitz L, Dezube BJ. HIV-associated plasmablastic lymphoma: Lessons learned from 112 published cases. Am J Hematol 2008;83:804-9.  Back to cited text no. 3
    
4.
Rafaniello Raviele P, Pruneri G, Maiorano E. Plasmablastic lymphoma: A review. Oral Dis 2009;15:38-45.  Back to cited text no. 4
    
5.
British HIV Association. Guidelines for HIV associated malignancies consultation draft. London: BHIVA; 2013. p. 63.  Back to cited text no. 5
    
6.
Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, et al. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: Impact of antiretroviral therapy suspension and tumor biology. Blood 2003;101:4653-9.  Back to cited text no. 6
    
7.
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999;17:1244.  Back to cited text no. 7
    
8.
Castillo JJ, Furman M, Beltra'n BE, Bibas M, Bower M, Chen W, et al. Human immunodeficiency virus-associated plasmablastic lymphoma: Poor prognosis in the era of highly active antiretroviral therapy. Cancer 2012;118:5270-7.  Back to cited text no. 8
    
9.
Valenzuela AA, Walker NJ, Sullivan TJ. Plasmablastic lymphoma in the orbit: Case report. Orbit 2008;27:227-9.  Back to cited text no. 9
    
10.
Mani D, Guinee DG Jr, Aboulafia DM. AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: A diagnostic dilemma. World J Gastroenterol 2008;14:4395-9.  Back to cited text no. 10
    
11.
Delecluse HJ, Anagnostopoulos I, Dallenbach F, Hummel M, Marafioti T, Schneider U, et al. Plasmablastic lymphomas of the oral cavity: A new entity associated with the human immunodeficiency virus infection. Blood 1997;89:1413-20.  Back to cited text no. 11
    
12.
Gérard L, Meignin V, Galicier L, Fieschi C, Leturque N, Piketty C, et al. Characteristics of non-Hodgkin lymphoma arising in HIV-infected patients with suppressed HIV replication. AIDS 2009;23:2301-8.  Back to cited text no. 12
    
13.
Besson C, Goubar A, Gabarre J, Rozenbaum W, Pialoux G, Châtelet FP, et al. Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. Blood 2001;98:2339-44.  Back to cited text no. 13
    
14.
Simonelli C, Zanussi S, Cinelli R, Dal Maso L, Di Genaro G, D'Andrea M, et al. Impact of concomitant antiblastic chemotherapy and highly active antiretroviral therapy on human immunodeficiency virus (HIV) viremia and genotyping in HIV-infected patients with non-Hodgkin lymphoma. Clin Infect Dis 2003;37:820-7.  Back to cited text no. 14
    
15.
Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, et al. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood 2003 Jun 15;101:4653-9.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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