Immunocompromised patients, including those infected with HIV, are at increased risk of developing malignancies. After Kaposi sarcoma, non-Hodgkin lymphomas are the most common malignant neoplasms affecting HIV-positive patients [1]. In addition to more routine lymphoid malignancies, HIV-positive patients are also predisposed to unique lymphoid malignancies (e.g. primary effusion lymphoma and large cell lymphoma arising in Kaposi virus-associated Castleman disease) that are rarely encountered in immunocompetent patients [2]. Plasmablastic lymphoma (PBL) is a rare and aggressive form of non-Hodgkin lymphoma originally described in 1997 [3]. Of the approximately 150 reported cases, PBL has most often been reported in the oral cavity of HIV-positive patients [1, 3–6]. Of the non-HIV-associated cases, one-third develop in patients with some other immunosuppressive condition such as steroid therapy or chemotherapy [6]. Like other HIV-associated lymphomas, the Epstein-Barr virus (EBV) is believed to play a role in the development of PBL [1, 3–6]. PBL is regarded as very aggressive neoplasm, and it usually presents at an advanced stage. Although the rarity of PBL has not permitted the development of a standardized treatment [4, 5], a combination of highly active anti-retroviral therapy and chemotherapy may lead to improved patient outcomes [5, 7].

A 44-year-old African American man presented with shortness of breath and right facial pain and swelling. His past medical history was remarkable for HIV infection with a history of non-compliance on highly active antiretroviral therapy. His CD4⁺ lymphocyte count was 160/μl. Although the facial mass had been present for ~2 months, the patient reported a dramatic increase in its size over the previous 3–4 days. Review of systems revealed that the patient had also lost about 30 lb over the past 3 months. On physical examination, a firm, rubbery, tender mass was palpated on the right cheek at the angle of the mandible. With the exception of poor dentition, the oral cavity and oropharynx were unremarkable. The initial clinical diagnosis was parotid sialadenitis, and the patient was prescribed antibiotics and corticosteroids.

PBL is an uncommon form of non-Hodgkin lymphoma that classically arises in the oral cavity of HIV-positive patients. PBL is a rapidly progressive lymphoma, and delay in treatment can adversely impact patient survival [7]. Although prompt and accurate recognition of PBL is imperative, the diagnosis of PBL is not easy due to a variety of contributing factors. First, PBL is rare, and its description as a distinct tumor entity is relatively recent. Prior to its original description in 1997 [3], most PBLs were likely diagnosed as CD20-negative large B cell lymphomas, intermediate forms of Burkitt lymphoma, or some poorly differentiated non-lymphoid malignancy [1, 3]. Indeed, even after its description as a distinct entity, Folk et al. [1] found that up to 40% of cases submitted for pathologic consultation were initially regarded as poorly differentiated carcinomas. Second, PBLs have an unusual immunophenotype that renders them susceptible to pathologic misdiagnosis. PBL is classified as a B cell lymphoma and its cellular morphology resembles immunoblastic diffuse large B-cell lymphoma, yet these tumors fail to consistently and strongly express leukocyte common antigen and the B cell markers CD20 and CD79a [1, 4, 8]. Diagnosis of PBL requires the use of additional markers to confirm plasmacytic differentiation. PBLs are immunoreactive for the plasmacytic markers CD138 and CD38. Unlike plasmacytomas, most PBLs are EBV related such that in situ hybridization for Epstein-Barr encoded RNA (EBER) is useful in distinguishing between these two plasma cell neoplasms [4, 6].