Rare AIDS-Associated Plasmablastic Lymphoma as the Initial Presentation of AIDS
Maqsood A. Khan, MD1, Shriram Jakate, MD, FRCPath2, Srinadh Komanduri, MD3
1West Suburban Hospital Medical Center, Oak Park, Illinois; 2Department of Pathology, Rush University Medical Center, Chicago, Illinois; 3Department of Gastroenterology, Northwestern University Medical Center, Chicago, Illinois
Introduction
Non-Hodgkin lymphoma (NHL) is the sixth leadingcause of cancer death in the United States and accounts for 2–3% of primary neoplasms.1 Plasmablastic lymphoma (PBL) is a rare AIDS-associated NHL of diffuse large B-cell lymphoma (DLBCL) type. It typically presents in HIV infection in the oral cavity.2 Here we discuss a case of a young woman who presented with PBL in the rectum as the initial manifestation of AIDS.
Case Report
A 40-year-old woman with no medical history presented to the emergency room with a Bartholin cyst; the cyst was excised and drained. Two months later, the patient presented with complaints of brown vaginal discharge that had persisted for approximately 2 weeks. She also complained of intermittent episodes of rectal bleeding. In the emergency room evaluation, a gynecologist identified a mass that extended onto the vaginal introitus. Another mass was noted during a rectal examination. A computed tomography (CT) scan of the abdomen and pelvis was obtained to evaluate for a possible enterovaginal fistula. It showed a large mass (10 cm x 9.8 cm) in the pelvis that extended from the vaginal introitus to the sacral promontory (Figure 1). Additionally, 3 soft tissue masses were attached to the large mass. They consisted of a central 4.8 cm x 4.7 cm mass, a mass measuring 2.8 cm x 4.7 cm located anterior to the external iliac artery, and a mass measuring 3.0 cm x 2.1 cm located lateral to the bladder. Ultrasound of the abdomen reidentified a large, ovoid, mixed echogenic mass measuring 8.9 cm x 9.9 cm x 8.6 cm.
The patient underwent staging work-up with CT of the chest and neck, which was negative. A bone marrow biopsy demonstrated hypercellular bone marrow with reactive plasmacytosis and increased hematopoiesis in all cell lines. No tumor or granuloma was seen. The patient began treatment with rituximab (Rituxan, Genentech), etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) therapy for plasmablastic lymphoma and highly active antiretroviral therapy (HAART) for HIV. Her vaginal discharge improved and she was discharged in stable condition.
Discussion
PBL most frequently presents in the oral cavity,3 with local invasion and rapid dissemination to extra-oral sites. It has also been reported in other sites such as the stomach, 4 cervical lymph nodes,5 lungs,6 orbit,7 and paranasal sinuses.8 Only a few cases of anorectal PBL have been reported.9-11 Although PBL has been reported mostly in patients with HIV infection, it can also be seen in immunocompromised patients who are HIV-negative.12
Extra-oral PBL is rare, but it has a similar invasive and rapidly disseminative capability as PBL of the oral cavity, and frequently presents as disseminated disease in HIV/AIDS individuals.11 Plasmablastic lymphoma can arise independently or against the background of human herpesvirus 8–driven multicentric Castleman’s disease. The characteristic immunophenotype includes the lack of expression of the pan B-cell antigen CD20, but includes expression of both MUM-1 and CD138, markers of plasma cell differentiation. Rearrangement of the immunoglobulin heavy chain is variable. The designation of PBL is based on plasmablastic morphology of the neoplastic cells, as well as an expression of plasma cell differentiation antigens.
Patients with HIV/AIDS are at a significantly increased risk of developing NHL, which is classified as an AIDS-defining illness. The most common types of AIDS-associated NHL are Burkitt lymphoma and DLBCL, which includes immunoblastic lymphoma. Rare types include primary effusion lymphoma (PEL), primary central nervous system lymphoma (PCNSL), and PBL. Viral activation is thought to play a significant role in the development of NHL in HIV patients. Evidence of Epstein-Barr virus infection is found in approximately 30% of Burkitt lymphoma patients, 40–90% of DLBCL, approximately 90% of PEL patients, almost all patients with PCNSL, and most patients with PBL.13 According to a recent series of patients with AIDS-associated NHL, PBL accounts for approximately 2–4% of all AIDSrelated lymphomas.13-15
Historically, the prognosis for patients with AIDSassociated PBL has been poor, with very few long-term survivors; however, the introduction of modern HAART appears to be associated with better prognoses in large series of patients with AIDS-related lymphomas.15,16 As in other types of NHLs, combination chemotherapy forms the backbone of therapy for PBL, and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimens are considered first-line therapy. Rituximab, an anti-CD20 monoclonal antibody that has been incorporated into the standard therapy for many B-cell NHLs, does not play a role in PBL therapy because CD20 is not usually expressed by PBL cells.
In addition, there is a case report of a patient with PBL who achieved remission with antiretroviral therapy alone, which suggests that there may be a role for immune reconstitution in the control of this aggressive lymphoma.17 Thus, initiating or continuing HAART as part of supportive therapy is recommended when treatment for HIV-positive patients with PBL is commenced. The occurrence of PBL in sites other than the oral cavity expands our knowledge of AIDS-related lymphoproliferative disorders and increases our insights into this rare entity. Pathologists should be aware that this tumor does appear in sites other than the oral cavity. Because of its cohesive histologic appearance, this tumor can be misinterpreted as a nonlymphoid tumor, particularly with the leukocyte common antigen negativity that is typical of this neoplasm.
References
1. Greenlee RT, Murray T, Bolden S, Wingo P. Cancer statistics, 2000. CA Cancer J Clin. 2000;50:7-33.
2. Gatter K, Warnke R. Diffuse large B-cell lymphoma. In: Jaffe E, Harris N, Stein H, Vardiman J, editors. World Health Organization Classification of Tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon7 IARC; 2001. 171- 174
3. Delecluse HJ, Anagnostopoulos I, Dallenbach F, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood. 1997;89:1413-1420.
4. Pruneri G, Graziadei G, Ermellino L, Baldini L, Neri A, Buffa R. Plasmablastic lymphoma of the stomach. A case report. Haematologica. 1998;83:87-89.
5. Lin F, Zhang K, Quiery AT, Jr, Prichard J, Schuerch C. Plasmablastic lymphoma of the cervical lymph nodes in a human immunodeficiency virus-negative patient: a case report and review of the literature. Arch Pathol Lab Med. 2004;128:581-584.
6. Lin Y, Rodrigues GD, Turner JF, Vasef MA. Plasmablastic lymphoma of the lung: report of a unique case and review of the literature. Arch Pathol Lab Med. 2001;125:282-285.
7. Valenzuela AA, Walker NJ, Sullivan TJ. Plasmablastic lymphoma in the orbit:case report. Orbit. 2008;27:227–229
8. Schichman SA, McClure R, Schaefer RF, Mehta P. HIV and plasmablastic lymphoma manifesting in sinus, testicles, and bones: a further expansion of the disease spectrum. Am J Hematol. 2004;77:291-295.
9. Colomo L, Loong F, Rives S, et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol. 2004;28:736-47.
10. Chetty R, Hlatswayo N, Muc R, Sabaratnam R, Gatter K. Plasmablastic lymphoma in HIV+ patients: an expanding spectrum. Histopathology. 2003;42:605- 9.
11. Dong HY, Scadden DT, de Leval L, Tang Z, Isaacson PG, Harris NL. Plasmablastic lymphoma in HIV-positive patients: an aggressive Epstein-Barr virusassociated extramedullary plasmacytic neoplasm. Am J Surg Pathol. 2005;29: 1633-1641.
12. Teruya-Feldstein J, Chiao E, Filippa DA, et al. CD20-negative large-cell lymphoma with plasmablastic features: a clinically heterogenous spectrum in both HIV-positive and -negative patients. Ann Oncol. 2004;15:1673-1679.
13. Carbone A, Gloghini A. AIDS-related lymphomas: from pathogenesis to pathology. Br J Haematol. 2005;130:662-670.
14. Carbone A, Gaidano G, Gloghini A, Ferlito A, Rinaldo A, Stein H. AIDSrelated plasmablastic lymphomas of the oral cavity and jaws: a diagnostic dilemma. Ann Otol Rhinol Laryngol. 1999;108:95-99.
15. Simonelli C, Spina M, Cinelli R, et al. Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol. 2003;21:3948-3954.
16. Lim ST, Karim R, Tulpule A, Nathwani BN, Levine AM. Prognostic factors in HIV-related diffuse large-cell lymphoma: before versus after highly active antiretroviral therapy. J Clin Oncol. 2005;23:8477-8482.
17. 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 43:2:423-426.