Indian Journal of Dental ResearchIndian Journal of Dental ResearchIndian Journal of Dental Research
HOME | ABOUT US | EDITORIAL BOARD | AHEAD OF PRINT | CURRENT ISSUE | ARCHIVES | INSTRUCTIONS | SUBSCRIBE | ADVERTISE | CONTACT
Indian Journal of Dental Research   Login   |  Users online: 234

Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size         

 


 
Table of Contents   
CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 5  |  Page : 559-562
Impact of highly active antiretroviral therapy in the development and remission of oral plasmablastic lymphoma


1 Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil
2 Department of Pathology, Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
3 Department of Oral Surgery, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil
4 Department of Oral Diagnosis, Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
5 Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Department of Oral Diagnosis, Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Click here for correspondence address and email

Date of Submission11-Apr-2016
Date of Decision22-May-2016
Date of Acceptance29-Jul-2016
Date of Web Publication13-Dec-2016
 

   Abstract 

Plasmablastic lymphoma (PBL) represents a rare type of non-Hodgkin lymphoma associated with human immunodeficiency virus (HIV) infection. The impact of highly active antiretroviral therapy (HAART) in this tumor is poorly known due to its small incidence. This study reports a case of a 33-year-old HIV-positive woman who was referred to the Stomatology Department complaining about a painful gingival growth and cervical nodule both with 20 days of evolution. The lesions appeared 7 months after the patient stopped HAART. The final diagnosis was PBL. After resuming HAART for 45 days, the gingival lesion presented complete remission. The patient continued with HAART alongside chemotherapy. At 24 months follow-up, the patient was stable. The dental surgeon plays an essential role in orientation and retention in care of HIV patients once the adherence of HAART seems to play an important role in PBL development and response to treatment.

Keywords: Acquired immunodeficiency syndrome, B-cell lymphoma, highly active antiretroviral therapy, human immunodeficiency virus infections

How to cite this article:
Wagner VP, Ortiz L, da Silva HP, Meurer L, da Cunha Filho JJ, Martins MA, Martins MD. Impact of highly active antiretroviral therapy in the development and remission of oral plasmablastic lymphoma. Indian J Dent Res 2016;27:559-62

How to cite this URL:
Wagner VP, Ortiz L, da Silva HP, Meurer L, da Cunha Filho JJ, Martins MA, Martins MD. Impact of highly active antiretroviral therapy in the development and remission of oral plasmablastic lymphoma. Indian J Dent Res [serial online] 2016 [cited 2019 Jan 18];27:559-62. Available from: http://www.ijdr.in/text.asp?2016/27/5/559/195687
According to the Joint United Nations Programme (UNAIDS), there are approximately 34.2 million people infected with human immunodeficiency virus (HIV) worldwide. [1] The reduced immunity among individuals with acquired immune deficiency syndrome (AIDS) increases the chance of developing diseases that originate from opportunistic pathogens. Therefore, infectious diseases, such as candidiasis, necrotizing ulcerative gingivitis, and herpes simplex, are among most prevalent AIDS-associated oral lesions. [2] Others include neoplastic diseases as AIDS-related lymphomas and Kaposi's sarcoma. The increment of highly active antiretroviral therapy (HAART) led to a significant decrease of AIDS-related morbidity and mortality.

AIDS-related lymphomas also presented a decline in incidence in the HAART-era coupled with a rise in overall survival when chemotherapy is associated with HAART. [3] Despite this considerable decrease in incidence, these lesions are still an important source of morbidity and mortality among HIV patients. AIDS-related lymphomas are predominantly aggressive high-grade B-cell lymphomas, such as Burkitt's lymphoma, diffuse large B-cell lymphoma, primary effusion lymphoma, and plasmablastic lymphoma (PBL). [3]

PBL was first described by Delecluse et al. as an aggressive variant of diffuse large B-cell lymphoma in HIV patients, presenting a high tropism for the oral cavity. [4] This rare lesion accounts for 2.6% of all AIDS-related lymphomas and even in the HAART-era is still associated with poor prognosis, presenting a median survival time of around 5 months. [4],[5] The aim of the present study is to report a case of PBL diagnosed in an HIV patient who interrupted HAART regimen with 24 months of follow-up. Moreover, a discussion of the impact of HAART in AIDS-related lymphomas, particularly in PBL, and the role of the dental surgeon in these cases are offered.


   Case report Top


A 33-year-old woman was referred to our Stomatology Department complaining about a painful gingival growth with 20 days of evolution. She was diagnosed with HIV-infection 12 years before and had been under HAART regimen (TDF + 3CT + ATZ/r) since then. The patient stopped HAART 7 months' earlier due to gastrointestinal adverse effects.

Extraoral examination revealed unilateral lymphadenopathy, with a single right submandibular lymph node palpable, firm, measuring 2 cm × 2 cm, and presenting diffuse pain in the cervical posterior region [Figure 1]a. Intraoral examination revealed an exophytic painful nodule in the gingiva extending from the vestibular region of teeth 45 and 46 to the lingual region [Figure 1]b. The teeth involved presented severe mobility. The patient referred noticing the gingival nodule and the cervical mass at the same time, around 20 days earlier. The periapical radiography revealed a destructive radiolucency with ill-defined borders leading to the erosion of the alveolar bone [Figure 2]. Based on clinical and radiographic aspects, the differential diagnosis included AIDS-related lymphomas, sarcomas, and oral squamous cell carcinoma with regional metastasis. An incisional biopsy of the gingival nodule was performed and the specimen was submitted to histopathological examination. The patient was advised to seek an infectologist to resume HAART.
Figure 1: (a) Extraoral examination revealed unilateral lymphadenopathy. (b) Intraoral examination revealed a gingival mass, sessile, and recovered by erythematous mucosa in the vestibular region. The lingual portion presented a pedicle and was ulcerated

Click here to view
Figure 2: Periapical radiography showing destructive radiolucency with ill-defined borders

Click here to view


Histopathological examination revealed a dense neoplastic plasma cell proliferation [Figure 3]a. Immunohistochemical analysis of neoplastic cells disclosed positivity to MUM-1 [Figure 3]b and CD138 [Figure 3]c. The cells showed negativity to leukocyte common antigen, CD3, CD4, CD5, CD7, CD10, CD20, CD79a, Bcl2, Bcl6, and cyclin-D1. Proliferation rate, assessed by Ki67/MIB-1 staining, was 80% [Figure 3]d. The findings were consistent with a PBL and the patient was referred to the Oncology Service for treatment.
Figure 3: (a) Histopathological examination showing neoplastic plasma cells presented sparse, darkly staining cytoplasm and pleomorphic, basophilic, and vesicular nuclei. Note the mitotic figures (*) and cells with eccentrically placed nucleus (arrows) (H and E, ×200). (b) Nuclear positivity for MUM-1 in more than 80% of neoplastic cells (LSAB, ×100). (c) Neoplastic cells presented membranous expression of CD138 (LSAB, ×100). (d) Proliferation rate, assessed by Ki67/MIB-1 nuclear labeling, was 80% (LSAB, ×100)

Click here to view


The patient consulted the infectologist and resumed HAART after the first visit at the Stomatology Department. At the first appointment in the Oncology Service, the patient was under HAART for about 45 days and presented complete remission of the gingival lesion [Figure 4]. Submandibular and submental palpable lymph nodes were detected. At this time, CD4 counting, CD4/CD8 ratio, and viral load were 314 cells/μL, 0.45, and 28.26 log 4.45, respectively. The patient referred losing 15 kg during the past 3 months, correspondent to 14.58% of her body mass. The patient was diagnosed with Stage IB and started treatment with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone associated with methotrexate, arabinoside-C, and dexamethasone for central nervous system chemoprophylaxis. At 24 months follow-up, the patient was stable and submandibular and submental palpable lymph nodes were not perceived; furthermore, new lesions were not clinically identified.
Figure 4: Intraoral aspects after the patient resumed highly active antiretroviral therapy and before chemotherapy treatment. Note the complete remission of the gingival lesion

Click here to view



   Discussion Top


HIV infection when untreated is inevitably fatal, with a median survival time from seroconversion of 8-10 years. Nevertheless, since the mid-1990s, the introduction of HAART led to a dramatic reduction in mortality in HIV patients. For this reason, HIV has now come to be considered more as a chronic disease instead of a fatal disease. In Brazil, the first middle-income country to provide free and universal access to HAART in 1996, the mortality rates declined 66.4% in HAART-era compared to non-HAART-era. [6] However, this improvement cannot be achieved without long-term optimal adherence and retention in care, which are the greatest challenges in the management of HIV/AIDS.

HAART adherence failure is directly associated with low survival rates in HIV patients. In the present case, the patient decided to stop HAART regimen approximately 1 year after having her second child due to severe gastrointestinal effects. It is important to notice that the patient underwent HAART regimen for 11 years before this decision. A retrospective clinical cohort demonstrated that postpartum period is associated with an increased risk of nonadherence to HAART, probably due to lifestyle changes or postpartum depression. [7] As a result of the central role that adherence plays in the effectiveness of HAART, it is extremely important to clarify to HIV patients about the potential consequences of nonadherence. The dentist, as a health-care provider, must be aware of this aspect. Dental practitioners usually have more knowledge about routes of HIV transmission than HIV pathogenesis, complications, and advances in treatment. [8] It is known that long-term interventions based on repetition and reinforcement are required to produce long-lasting adherence. Therefore, HIV patients should benefit from all opportunities with dental practitioners for reinforcement of the gravity of HAART nonadherence.

Non-Hodgkin lymphoma risk is still greatly elevated in HIV-positive individuals compared to the general population; nevertheless, AIDS-related lymphomas experienced a noticeable decline in incidence in the HAART-era, [3] demonstrating the effectiveness of recovering immune function on the pathogenesis of these lesions. PBL represent only 2.6% of AIDS-related lymphomas. It presents a marked male predilection (5.7:1) and in the majority of cases presents with intraoral involvement at the time of initial diagnosis. PBL is strongly associated with HIV-infection and among those cases, around 74% with EBV infection present. [4],[5]

Previous reports in literature demonstrated that HAART interruption was associated with PBL development and recurrence. [9] Herein, the patient noticed that the lesion appeared about 7 months after stopping HAART treatment. These findings suggest that the reduction in immune response experienced by patients during HAART interruption might be determinant for the development of malignant tumors, such as PBL. In the present case, the patient presented complete remission of the gingival lesion only with HAART resumption. Nevertheless, the nodal lesion was still present after 45 days on HAART regimen. Corti et al. reported a case of a PBL patient that responded to HAART alone and remained in remission after 10 months without requiring chemotherapy. [10] Similar events were reported by others, [11] which demonstrated that even after established malignant disease, recovery of immune function may be decisive on partial, as describe herein, or total remission of HIV-associated PBL.

The median survival time for PBL is around 4 months after diagnosis. [5] At first description of PBL, Delecluse et al. found that all PBL patients were deceased at 12 months follow-up. [4] Cohort studies fail to demonstrate an improvement on PBL prognosis in HAART-era, [5] while the overall survival of other types of AIDS-related lymphomas increased more than two-fold in HAART-era. [3] PBL is an extremely rare tumor, leading to small samples as consequence. Guan et al., in a meta-analysis comprehending 10 randomized clinical trials, were able to demonstrate that prognosis and survival of PBL patients receiving HAART in addition to chemotherapy and/or radiotherapy were improved compared to patients receiving chemotherapy and/or radiotherapy alone. [12] In the present study, the patient was stable with 24 months of follow-up. This finding translates what was reported herein by other authors who also found that HIV-positive PBL patients treated with chemotherapy associated with HAART present longer survival rates. [13] The reason for this may rely on the fact that antiretroviral therapy can restore immune surveillance allowing a more efficient anticancer effect of chemotherapy.

Reduction in immune response seems to play a role in PBL pathogenesis. Moreover, immune reconstitution secondary to HAART was associated with partial remission and appears to be related with improvement of overall survival. These findings reveal the major importance of HAART adherence regarding the development and treatment of PBL. The presence of oral diseases can be a signal of decline in immune system function. The role of dental surgeon, however, goes beyond the diagnosis and is also associated with orientation and retention in care of HIV patients, thus improving both quality of life and survival for these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
UN Joint Programme on HIV/AIDS (UNAIDS), Global Report: UNAIDS Report on the Global AIDS Epidemic: 2013; December, 2013. Available from: http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Global_Report_2013_en_1.pdf. [Last accessed on 2015 Sep 20].  Back to cited text no. 1
    
2.
Lourenço AG, Motta AC, Figueiredo LT, Machado AA, Komesu MC. Oral lesions associated with HIV infection before and during the antiretroviral therapy era in Ribeirão Preto, Brazil. J Oral Sci 2011;53:379-85.  Back to cited text no. 2
    
3.
Diamond C, Taylor TH, Aboumrad T, Anton-Culver H. Changes in acquired immunodeficiency syndrome-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: Incidence, presentation, treatment, and survival. Cancer 2006;106:128-35.  Back to cited text no. 3
    
4.
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. 4
    
5.
Schommers P, Wyen C, Hentrich M, Gillor D, Zoufaly A, Jensen B, et al. Poor outcome of HIV-infected patients with plasmablastic lymphoma: Results from the German AIDS-related lymphoma cohort study. AIDS 2013;27:842-5.  Back to cited text no. 5
    
6.
Tancredi MV, Waldman EA. Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: A cohort study. BMC Infect Dis 2014;14:599.  Back to cited text no. 6
    
7.
Henegar CE, Westreich DJ, Maskew M, Miller WC, Brookhart MA, Van Rie A. Effect of pregnancy and the postpartum period on adherence to antiretroviral therapy among HIV-infected women established on treatment. J Acquir Immune Defic Syndr 2015;68:477-80.  Back to cited text no. 7
    
8.
Rungsiyanont S, Lam-Ubol A, Vacharotayangul P, Sappayatosok K. Thai dental practitioners′ knowledge and attitudes regarding patients with HIV. J Dent Educ 2013;77:1202-8.  Back to cited text no. 8
    
9.
Francischini E, Martins FM, Braz-Silva PH, Magalhães MH, Ortega KL. HIV-associated oral plasmablastic lymphoma and role of adherence to highly active antiretroviral therapy. Int J STD AIDS 2010;21:68-70.  Back to cited text no. 9
    
10.
Corti M, Villafañe MF, Bistmans A, Campitelli A, Narbaitz M, Baré P. Oral cavity and extra-oral plasmablastic lymphomas in AIDS patients: Report of five cases and review of the literature. Int J STD AIDS 2011;22:759-63.  Back to cited text no. 10
    
11.
Lester R, Li C, Phillips P, Shenkier TN, Gascoyne RD, Galbraith PF, et al. Improved outcome of human immunodeficiency virus-associated plasmablastic lymphoma of the oral cavity in the era of highly active antiretroviral therapy: A report of two cases. Leuk Lymphoma 2004;45:1881-5.  Back to cited text no. 11
    
12.
Guan B, Zhang X, Ma H, Zhou H, Zhou X. A meta-analysis of highly active anti-retroviral therapy for treatment of plasmablastic lymphoma. Hematol Oncol Stem Cell Ther 2010;3:7-12.  Back to cited text no. 12
    
13.
Panos G, Karveli EA, Nikolatou O, Falagas ME. Prolonged survival of an HIV-infected patient with plasmablastic lymphoma of the oral cavity. Am J Hematol 2007;82:761-5.  Back to cited text no. 13
    

Top
Correspondence Address:
Manoela Domingues Martins
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Department of Oral Diagnosis, Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90035-903
Brazil
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.195687

Rights and Permissions


    Figures

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



 

Top
 
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


    Abstract
   Case report
   Discussion
    References
    Article Figures

 Article Access Statistics
    Viewed1093    
    Printed17    
    Emailed0    
    PDF Downloaded44    
    Comments [Add]    

Recommend this journal