Editorial comment: plasmablastic lymphoma--a diagnostic and therapeutic puzzle.

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.