nosis of PBL of the gingiva in an apparently healthyindividual, who was previously undiagnosed of HIVdisease.

References1. Porter SR, Dios PD, Kumar N, et al: Oral plasmablastic lym-

phoma in previously undiagnosed HIV disease. Oral Surg OralMed Oral Pathol Oral Radiol Endod 87:730, 1999

2. Beral V, Peterman T, Berkelman R, et al: AIDS-associated non-Hodgkin’s lymphoma. Lancet 337:805, 1990

3. Flaitz CM, Nichols CM, Walling DM, et al: Plasmablastic lym-phoma: An HIV-associated entity with primary oral manifesta-tions. Oral Oncology 38:96, 2002

4. Lozada-Nur F, De Sanz S, Silverman S Jr, et al: Intraoral non-Hodgkin’s lymphoma in seven patients with acquired immuno-deficiency syndrome. Oral Surg Oral Med Oral Pathol OralRadiol Endod 82:173, 1996

5. Slootweg PJ, Wittkampf ARM, Kluin PM, et al: Extranodal non-Hodgkin’s lymphoma of the oral tissue: An analysis of 20 cases.J Maxillofac Surg 13:85, 1985

6. Wolvius EB, Schulten EAJM, Vander Waal I: Non-Hodgkin’slymphoma of the oral cavity as the first manifestation of AIDS.Br Dent J 182:107, 1997

7. Jordan LB, Lessells AM, Goodlad JR: Plasmablastic lymphomaarising at a cutaneous site. Histopathology 46:108, 2005

8. Delecluse HJ, Anagnostopoulos I, Dallenbach H, et al: Plasma-blastic lymphomas of the oral cavity: A new entity associatedwith the human immunodeficiency virus infection. Blood 89:1413, 1997

9. Feldstein JT, Chiao E, Flippa DA, et al: CD20 negative large celllymphoma with plasmablastic features: A clinically heteroge-nous spectrum in both HIV positive and negative patients. AnnOncol 15:1673, 2004

10. Scheper MA, Nikitakis NG, Fernandes R, et al: Oral plasmablas-tic lymphoma in an HIV-negative patient: A case report andreview of the literature. Oral Surg Oral Med Oral Pathol OralRadiol Endod 100:198, 2005

J Oral Maxillofac Surg65:1361-1364, 2007

Spontaneous Regression of anHIV-Associated Plasmablastic Lymphoma

in the Oral Cavity: A Case ReportRobert Armstrong, DMD,* Jon Bradrick, DDS,†

and Yao-Chang Liu, MD‡

Plasmablastic lymphoma (PBL) is a rare variant of adiffuse B-cell lymphoma that is most commonlyfound in the oral cavity affecting the mucosa, andso named for its blastoid morphology and immuno-phenotype.1,2 These tumors are found in patientswith human immunodeficiency virus (HIV), affect-ing approximately 3% of all HIV patients.3,4 It is notatypical to find non-Hodgkin’s lymphomas (NHL)associated with acquired immunodeficiency syn-drome (AIDS) and in some cases its manifestationdelineates an HIV-positive patient as having AIDS.1

As a distinct subset, PBLs are noted to be rapidlyprogressive with a high mitotic index.5Althoughprognosis is usually poor, with an average survivaltime being approximately 6 months,1,2,6 there havebeen reports of cases of using highly active anti-retroviral therapy (HAART) as well as traditionallymphoma therapy with complete remission.3,7,8

There are currently very few reported cases ofclinical remission with HAART alone.

Report of a Case

The patient is a 35-year-old man with a past medicalhistory significant for HIV infection who was referred toour department (Oral and Maxillofacial Surgery, Metro-Health Medical Center, Cleveland, OH) in May 2005 froman outside facility with what was described as an odon-togenic infection of the left maxilla. In addition to hisHIV status, his only other contributing health history wasa previous episode of Pneumocystitis carinii pneumoniaand oral thrush (both secondary to his immunodeficiencyand both treated and resolved before his presentation).He reported quitting the use of alcohol and smokingcigarettes approximately 5 years earlier. His CD4 count atthe time of presentation was 296 cells/�L and his viralload was undetectable. He was started on HAART inJanuary 2005 (consisting of atazanavir sulfate [Reyataz, Bristol-Myers Squibb, New York, NY], ritonavir [Norvir, Abbott Lab-

Received from the MetroHealth Medical Center in affiliation with

Case Western Reserve University, Cleveland, OH.

*Resident, Department of Oral and Maxillofacial Surgery.

†Associate Professor, Department of Surgery; Director of Oral

and Maxillofacial Surgery.

‡Associate Professor, Department of Pathology.

Address correspondence and reprint requests to Dr Armstrong:

Department of Oral and Maxillofacial Surgery, MetroHealth Medical

Center, 2500 MetroHealth Dr, Cleveland, OH 44109; e-mail:

rtarmstrong@gmail.com

© 2007 American Association of Oral and Maxillofacial Surgeons

0278-2391/07/6507-0017$32.00/0

doi:10.1016/j.joms.2005.12.039

ARMSTRONG, BRADRICK, AND LIU 1361

oratories, Abbott Park, IL], and lamivudine [Combivir, Glaxo-SmithKline, Research Triangle Park, NC]). Before HAART, hehad a low CD4 count (37 cells/�L) with a high viral load(�750,000 virons/mL). His initial symptoms began in Octo-ber 2004, at which time he was noted to have pain in thearea of the left maxillary molar region. He underwent ex-traction by another surgeon of what was thought to be anoffending tooth. Over the ensuing months the pain re-solved; however, the lesion continued to increase in sizeand was interfering with his ability to eat normally. Duringhis initial exam he was noted to have a friable purple-redfungating mass approximately 3 cm � 5 cm at the posteriorof the left maxillary arch (Fig 1A). The lesion was nonfluc-tuant and nontender to palpation. Panoramic radiographrevealed significant bone loss of the left maxilla (Fig 2). Anincisional biopsy was obtained using a biopsy forceps. Thespecimen was subjected to various immunohistochemicalstudies (Table 1), revealing the cells were focally positivefor CD79a. A Ki-67 stain showed a labeling index of approx-imately 50%. The cells were negative for CD3, CD10, CD31,CD45, Keratin, HMB45, and CD30. CD20 was only faintlypositive. These findings were confirmed by a separate pa-thology department at the Cleveland Clinic Foundation

where additional immunostains for CD138 and VS38c wereperformed, revealing the cells are strongly positive forCD138 and VS38c. The cells were found to be negative forCD20 at this facility. The ALK1 stain was determined to benegative at both facilities. Epstein-Barr virus-encoded RNAin situ hybridization demonstrated approximately 50% ofneoplastic B cells positive for Epstein-Barr virus. The histo-logic sections showed sheets of atypical large lymphoidcells with moderate amounts of eosinophilic cytoplasmwith some cells having plasmacytic to immature plasmablas-tic features (Fig 3). The final pathology report from bothfacilities rendered the diagnosis of HIV-associated plasma-blastic variant of diffuse large B-cell lymphoma or PBL (byWorld Health Organization classification).

The patient returned to our clinic after 1 week. He wasnoted to have a marked decrease in size of the lesionand the mucosal tissue appeared more normal in coloring(Fig 1B). The lesion remained nontender and he reportedbeing able to eat normally. Computed tomography scanof the midface showed advanced bony deterioration ofthe left maxillary alveolus extending into the left maxil-lary sinus (Fig 2A).

FIGURE 1. Clinical photographs of the lesion. A, Initial presentation. B,Lesion at 7 days postoperative; and C, at 21 days postoperative.

Armstrong, Bradrick, and Liu. Spontaneous Regression of an HIV-Associated PBL. J Oral Maxillofac Surg 2007.

1362 SPONTANEOUS REGRESSION OF AN HIV-ASSOCIATED PBL

At 2 weeks the patient manifested no clinical evidenceof gross pathology aside from a 3 mm � 3 mm firm,bluish area along the buccal aspect of the maxillary ridge(Fig 1C). Multiple new incisional biopsies were obtainedfrom the oral mucosal site using a biopsy forceps. Flowcytometry immunophenotype studies were ordered,which showed no residual lymphoma population. Be-cause of the aggressive nature of this process, chemo-therapy was initiated by the referring facility. However,his clinical course showed marked improvement, withnear total remission before starting his therapy. A bonemarrow aspiration and core biopsy were obtained andrevealed no lymphoma involvement. He also had no evi-dence of extranodal involvement on computed tomogra-phy of the chest, abdomen, and pelvis. A liver needlebiopsy showed no evidence of malignancy. However,scattered non-necrotizing granulomas were noted in thespecimen, which was interpreted as a systemic responseto lymphoma. At 1 month from the time of his initialevaluation in our clinic he was completely devoid of anyclinical symptoms.

Discussion

HIV-infected individuals are at an increased risk ofdeveloping a NHL. It has been reported that they areas much as 120 to 157 times more likely to developNHL when compared with the general popula-tion.2,4,6 PBL is a recently described entity and ac-counts for a very small percentage of HIV-associatedNHLs. Epstein-Barr virus and human herpesvirus type8 have been detected in the majority of oral PBLs ofpatients with AIDS.1,5-10 Unlike most HIV-associatedB-cell lymphomas, PBLs express a unique immuno-phenotype that does not express or faintly expressesthe common lymphoid antigen CD20.2 The tumorcells were strongly positive for the plasma cell-relatedantibody VS38c and CD138, both of which help dis-tinguish this tumor as a PBL.2,11 The oddity of thiscase is not in its presentation or histopathology, but

FIGURE 2. A, Three-dimensional CT reconstruction. B, Panoramicradiograph showing marked bony invasion of the lesion.

Armstrong, Bradrick, and Liu. Spontaneous Regression of anHIV-Associated PBL. J Oral Maxillofac Surg 2007.

Table 1. RESULTS OF IMMUNOHISTOCHEMICAL STAINS FROM OUR FACILITY AND THE REFERRING FACILITY

Antibody Our Facility Referring Facility

Keratin Negative NegativeHMB-45 Negative NegativeLCA Focally positive Not testedCD3 Negative NegativeCD10 Not tested NegativeCD20 Positive in 20% NegativeCD79 Positive in 50% Focally positiveCD31 Negative NegativeCD45 Not tested NegativeALK Cytoplasmic staining in 20% NegativeCD30 Negative NegativeKi-67 Positive in 80% Positive in 50%Kappa & Lamba light chains Negative—using immunohistochemistry

methodNegative—using immunohistochemistry method and

noncontributary—using in situ methodVS38c Not tested Strongly positive

Armstrong, Bradrick, and Liu. Spontaneous Regression of an HIV-Associated PBL. J Oral Maxillofac Surg 2007.

ARMSTRONG, BRADRICK, AND LIU 1363

rather in the spontaneity of its complete clinical re-gression without chemotherapy. Recognizing thisatypical course for a neoplastic process, other diseaseprocesses were considered in the differential diagno-sis. However, other entities, including infectiousmononucleosis, do not carry with it this immunophe-notype and histologic morphology.

In the reported case by Lester,3 he notes the pos-sibility of PBL being part of an immune reconstitutionsyndrome. He noted in his patient, as with 3 otherreported cases by Collazos et al,7 the diagnosis of PBLcame 8 to 12 weeks after the initiation of HAART.However, in our case as well as Lester’s, the initialsymptoms were found to pre-date the onset ofHAART, suggesting that it was a pre-existing condition.Lester suggested that immune reconstitution may havecontributed to an initial clinical progression.

Spontaneous regression of high-grade lymphomasin HIV-infected patients is very uncommon and hasbeen rarely reported in the literature. We speculatethis regression might be at least partially related to thepatient’s restoration of immune function secondary tohis antiretroviral usage. It has been well documentedthat in patients who develop post-transplant lympho-proliferative disorders, particularly in low-grade le-sions such as plasmacystic hyperplasia and polymor-phic post-transplant lymphoproliferative disorders, areduction in immunosuppression leads to regressionin many of the cases.12,13 Histologically, the HIV-associated PBL closely resembles those post-trans-

plant lymphoproliferative disorders referred to as“plasmacytic hyperplasia.”14 In our patient, he wasnoted to have a CD4 count before the onset of HAARTof 37 cells/�L with a progression to 296 cells/�L atthe time of regression of his oral lesion and afterinitiation of HAART. This clinical outcome, along withsimilar outcomes of HIV-positive patients receivingHAART with restoration of immune status as well aspatients with post-transplant lymphoproliferativedisorders that have discontinued use of immuno-suppressants, indicates the correlation betweencontrol of immune function and the outcomes ofthese tumors.

References1. Cioc AM, Allen C, Kalmar JR, et al: Oral plasmablastic lympho-

mas in AIDS patients are associated with human herpesvirus 8.Am J Surg Pathol 28:41, 2004

2. Delecluse HJ, Anagnostopoulos F, Dallenbach M, et al: Plasma-blastic lymphomas of the oral cavit: A new entity associatedwith the human immunodeficiency virus infection. Blood 89:1413, 1997

3. Lester R: Improved outcome of human immunodeficiencyvirus-associated plasmablastic lymphoma of the oral cavity inthe era of highly active antiretroviral therapy: A report of twocases. Leuk Lymphoma 45:1881, 2004

4. Kumar V, Robbins S, Cotran R: Pathologic Basis of Disease. Ed7. Philadelphia, PA, Elsevier, 2005

5. Jaffe E, Harris N, Stein H, et al: Pathology and Genetics ofTumors of Haematopoietic and Lymphoid Tissues. Lyon, IARCPress, 2001

6. Flaitz CM, Nichols CM, Walling DM, et al: Plasmablastic lym-phoma: An HIV-associated entity with primary oral manifesta-tions. Oral Oncology 38:96, 2002

7. Collazos J, Ojanguren J, Mayo J, et al: Lymphoma developingshortly after the onset of highly active antiretroviral therapy inHIV-infected patients. AIDS 16:1304, 2002

8. Nasta SD, Carrum GM, Shahab I, et al: Regression of a plasma-blastic lymphoma in a patient with HIV on highly active anti-retroviral therapy. Leuk Lymphoma 43:423, 2002

9. Brown RSD, Power DA, Spittle HF, et al: Absence of immuno-histochemical evidence for Human Herpesvirus 8 in oral cavityplasmablastic lymphoma in HIV-positive man. Clin Oncology12:194, 2000

10. Gustaffson EA, Schriazi RF, Fingeroth JD: Human Herpesvirus 8Open Reading Frame 21 is a thymidine and thymidilate kinaseof narrow substrate specificity that efficiently phosphorylateszidovudine but not ganciclovir. J Virol 74:684, 2000

11. Chetty R, Hlatswayo N, Muc R, et al: Plamablastic lymphoma inHIV� patients: An expanding spectrum. Histopathology 42:605, 2003

12. Nador R, Chadburn A, Gundappa G, et al: Human immunode-ficiency virus (HIV)-associated polymorphic lymphoprolifera-tive disorders. Am J Surg Pathol 27:293, 2003

13. Nalesnik MA, Jaffe R, Starzi TE, et al: The pathology of post-transplant lymphoproliferative disorders occurring in the set-ting of cyclosporine A-prednisone immunosuppression. Am JPathol 133:173, 1988

14. Knowles DM, Cesarmen E, Chadburn A, et al: Correlative mor-phologic and molecular genetic analysis demonstrates threedistinct categories of posttransplantation lymphoproliferativedisorders. Blood 85:552, 1995

FIGURE 3. Histologic section showing diffuse infiltration of largeatypical lymphoid cells with prominent nucleoli, some with plasmacy-toid differentiation, scattered apoptotic bodies, and increased mitoticindex. (Hematoxylin-eosin stain; magnification �400.)

Armstrong, Bradrick, and Liu. Spontaneous Regression of anHIV-Associated PBL. J Oral Maxillofac Surg 2007.

1364 SPONTANEOUS REGRESSION OF AN HIV-ASSOCIATED PBL