Editorial Comment: Plasmablastic Lymphoma-A Diagnostic and Therapeutic Puzzle

The AIDS ReaderThe AIDS Reader Vol 17 No 9
Volume 17
Issue 9

Oral cavity lymphoma occurs frequently in HIV-positive patients, often with a poor prognosis.1 Ortega and colleagues2 present an enlightening case of a destructive oral plasmablastic lymphoma in a 43-year-old HIV-positive man. Similar to another recently reported case,3 this lymphoma was their patient's first manifestation of his underlying HIV infection.

Oral cavity lymphoma occurs frequently in HIV-positive patients, often with a poor prognosis.1 Ortega and colleagues2 present an enlightening case of a destructive oral plasmablastic lymphoma in a 43-year-old HIV-positive man. Similar to another recently reported case,3 this lymphoma was their patient's first manifestation of his underlying HIV infection.

Plasmablastic lymphoma is a unique AIDS-related lymphoma, which was first described in the jaws and oral cavity of HIV-infected persons about a decade ago.4,5 Awareness of this distinctive lymphoma can prevent misdiagnosis by the clinician (eg, as odontogenic cellulitis) or the pathologist (eg, as a nonlymphoid malignancy). Since the original reports of plasmablastic lymphoma, it has been described in several other sites, including the GI tract (particularly the anorectum), omentum, lung, nasal and paranasal regions, testes, bones, soft tissue, lymph nodes, bone marrow, skin, and CNS.6-11 Plasmablastic lymphoma has also been documented to arise from long-standing sacrococcygeal cysts in HIV-positive persons.12

Plasmablastic lymphoma accounts for 2.6% of all HIV-related non-Hodgkin lymphomas.13 This lymphoma has also been reported in HIV-negative persons, particularly those who have immunosuppression. Plasmablastic lymphoma usually develops in middle-aged adults, with the age at onset in one large series varying from 35 to 55 years,13 but it can also occur in the pediatric age group.14

There are 3 recognized categories of plasmablastic lymphoma.15-17 The first type is plasmablastic lymphoma of oral mucosa. Such lymphomas contain a monomorphic population of plasmablasts with no or minimal plasmacytic differentiation. They are found largely in the oral mucosa but also may occur in other extranodal or nodal sites. The second type is plasmablastic lymphoma with plasmacytic differentiation. These extraoral lymphomas are composed predominantly of plasmablasts but exhibit more differentiation to mature plasma cells than is seen in the first type. The third kind is plasmablastic lymphoma associated with Castleman disease,18,19 which is typically nodal or splenic.

Plasmablastic lymphoma is listed in the World Health Organization 2001 classification as a variant of diffuse large B-cell lymphoma.20 The histological findings of a diffuse infiltrative growth pattern, brisk mitotic activity, and necrosis, along with the fact that they are rapidly growing destructive tumors, supports their designation as a high-grade malignant lymphoma.

Based on a similar morphology and behavior, plasmablastic lymphoma needs to be distinguished from the immunoblastic variant of diffuse large B-cell lymphoma, classic (body cavity-based) and solid (extracavitary) variants of primary effusion lymphoma, Burkitt lymphoma with plasmacytoid differentiation, and extramedullary plasmablastic tumors secondary to multiple myeloma or plasmacytomas.21 Plasmablastic lymphoma is characterized by immunoblastic morphology and plasma cell phenotype. In other words, plasmablasts are lymphoid cells that morphologically resemble B-cell immunoblasts but have acquired a plasma cell immunophenotype (ie, loss of B-cell markers and surface immunoglobulin with the acquisition of plasma cell surface markers). Thus, unlike immunoblasts, plasmablasts fail to express CD45 (leukocyte common antigen) as well as the B-cell marker CD20 and are only variably immunoreactive for CD79a-a broader-spectrum B-cell marker. They are also negative for pan–T-cell markers. Positive staining for plasma cell markers such as VS38c, CD38, MUM-1, and CD138 indicates a phenotype akin to plasma cells.21,22 Newer B-lineage markers (eg, OCT.2 and BOB.1) may prove useful in determining a B-cell origin in plasmablastic lymphomas.

While it is established that most plasmablastic lymphomas are positive for Epstein-Barr virus (EBV), the role of human herpesvirus 8 (HHV8) in their lymphomagenesis remains somewhat unresolved. Like EBV, HHV8 is a lymphotropic gammaherpesvirus. Originally, it was reported that plasmablastic lymphomas were negative for HHV8 using immunohistochemistry,5 and this was confirmed by subsequent studies.23,24 However, other investigators have detected HHV8 RNA in oral plasmablastic lymphomas by using polymerase chain reaction methods.9,25 The association of plasmablastic lymphoma with HHV8 certainly helps explain why, over time, some of these tumors arise from the HHV8-related plasmablastic variant of Castleman disease seen in HIV-infected patients. Documentation of the development of Kaposi sarcoma, Castleman disease, and plasmablastic lymphoma simultaneously in patients suggests a critical role of HHV8 as a common denominator in the pathogenesis of all of these diseases.26

The growing body of literature dealing with the clinical outcome and treatment of plasmablastic lymphoma is puzzling. Published data indicate that these are aggressive tumors, frequently resistant to therapy, and often rapidly fatal.27 Moreover, in the setting of HIV infection, plasmablastic lymphoma has been shown to evolve into plasmablastic leukemia.28 Available data from the pre-HAART era showed that plasmablastic lymphoma carried a poor prognosis, with a dismal median survival of about 5 months.29 Therefore, it is unclear why in certain immunodeficient hosts, spontaneous regression30 or prolonged survival31,32 has been reported. Ortega and colleagues treated their patient with antiretroviral therapy; however, we do not know the outcome. To date, there have been very few case reports suggesting that the prognosis of plasmablastic lymphoma may be improved following antiretroviral therapy.33-35 Hopefully, there will be larger trials investigating the potential beneficial role of antiretrovirals in treating this novel lymphoma.

Liron Pantanowitz, MD
Assistant Professor of Pathology
Baystate Medical Center
Tufts University School of Medicine
Springfield, Mass

Bruce J. Dezube, MD
Associate Professor of Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School

No potential conflict of interest relevant to this commentary was reported by the authors.


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13. Folk GS, Abbondanzo SL, Childers EL, Foss RD. Plasmablastic lymphoma: a clinicopathologic correlation. Ann Diagn Pathol. 2006;10:8-12.
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17. Tavora F, Gonzalez-Cuyar LF, Sun CC, et al. Extra-oral plasmablastic lymphoma: report of a case and review of literature. Hum Pathol. 2006;37:1233-1236.
18. Dupin N, Diss TL, Kellam P, et al. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. Blood. 2000;95:1406-1412.
19. Oksenhendler E, Boulanger E, Galicier L, et al. High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood. 2002;99:2331-2336.
20. Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization WHO Classification of Tumours, Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Lyon, France: IARC Press; 2001:257-263.
21. Jaffar SA, Pihan G, Dezube BJ, Pantanowitz L. Differentiating HIV-associated lymphomas that exhibit plasmacellular differentiation. HIV AIDS Rev. 2005;4:43-49.
22. Carbone A, Gloghini A, Larocca LM, et al. Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. Blood. 2001;97:744-751.
23. Vega F, Chang CC, Medeiros LJ, et al. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod Pathol. 2005;18:806-815.
24. Brown RS, Power DA, Spittle HF, Lankester KJ. Absence of immunohistochemical evidence for human herpesvirus 8 (HHV8) in oral cavity plasmablastic lymphoma in an HIV-positive man. Clin Oncol. 2000;12:194.
25. Carbone A, Gloghini A, Gaidano G. Is plasmablastic lymphoma of the oral cavity an HHV-8-associated disease? Am J Surg Pathol. 2004;28:1538-1540.
26. Cioc AM, Allen C, Kalmar JR, et al. Oral plasmablastic lymphomas in AIDS patients are associated with human herpesvirus 8. Am J Surg Pathol. 2004;28:41-46.
27. Liu W, Lacouture ME, Jiang J, et al. KSHV/HHV8-associated primary cutaneous plasmablastic lymphoma in a patient with Castleman’s disease and Kaposi’s sarcoma. J Cutan Pathol. 2006;33(suppl 2):46-51.
28. Goedhals J, Beukes CA, Cooper S. The ultrastructural features of plasmablastic lymphoma. Ultrastruct Pathol. 2006;30:427-433.
29. Jung CP, Horster S, Lohse P, et al. Uncommon hematologic malignancies. Case 1. Plasmablastic leukemia in HIV-associated multicentric Castleman’s disease. J Clin Oncol. 2003;21:4248-4249.
30. Navarro WH, Kaplan LD. AIDS-related lymphoproliferative disease. Blood. 2006;107:13-20.
31. Armstrong R, Bradrick J, Liu YC. Spontaneous regression of an HIV-associated plasmablastic lymphoma in the oral cavity: a case report. J Oral Maxillofac Surg. 2007;65:1361-1364.
32. Horster S, Jung C, Zietz C, et al. AIDS, multicentric Castleman’s disease, and plasmablastic leukemia: report of a long-term survival. Infection. 2004;32:296-298.
33. 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;82:761-765.
34. Nasta SD, Carrum GM, Shahab I, et al. Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy. Leuk Lymphoma. 2002;43:423-426.
35. Lester R, Li C, Phillips P, Shenkier TN, 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;45:1881-1885.

No potential conflict of interest relevant to this commentary was reported by the authors.

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