Plasmablastic lymphoma, originally described in 1997 by Delecluse et al. [
4] is an aggressive variant of diffuse large B-cell non-Hodgkin lymphoma seen predominantly in a setting of AIDS and nearly always in extranodal sites. Subsequently, other cases have been reported, mostly in a setting of AIDS or together with iatrogenic immune suppression or advanced age [
1]. Sites outside the oral cavity have been described, including the anorectal region [
2], skin [
10,
12], lung [
11], and breast [
16]. One previous report has described the occurrence of a primary central nervous system (CNS) PBL in an AIDS patient as a well-defined, hyperdense, contrast enhancing mass in the right basal ganglia with extensive peritumoral edema and mass effect [
13]. Our report is the first to describe the previously unrecognized primary leptomeningeal form of PBL in an AIDS patient. Interestingly this was associated with CNS cyptococcosis suggesting a role for chronic antigen stimulation in its pathogenesis. Such association of NHLs with chronic infection including viral infections (EBV, HHV8) as well as chronic tuberculous pyothorax is known to occur [
9].
Lymphomas in HIV patients are heterogenous and reflect several pathogenetic mechanisms such as chronic antigen stimulation, multiple genetic alterations, and cytokine dysregulation. 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. 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 (i.e, loss of B-cell markers and surface immunoglobulin with the acquisition of plasma cell surface markers) [
13]. 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 [
13]. PBL has been etiologically linked to Epstein-Barr virus, Kaposi Sarcoma human virus, and human herpesvirus type-8 infections in addition to HIV [
3,
5]. Microscopic examination shows infiltrates of large atypical plasmacytoid cells with abundant cytoplasm, round nuclei, and occasional, centrally located, prominent nucleoli [
14]. Several different immunohistochemical markers have been used in an attempt to characterize these lesions [
6]. Of these CD 138 is most consistently positive and indicates plasma cell differentiation of the tumor cells [
6,
8]. Immunoglobin heavy and light chain restrictions are often present [
2,
15]. Ultrastructural features under electron microcopy include round nuclei with clumped heterochromatin and large nucleoli, with concentrically arranged rough endoplasmic reticulum in the cytoplasm [
7].
HIV associated PBL has been treated with a variety of chemotherapeutic agents, but the efficacy of treatment is unclear. The previously reported case of CNS PBL was treated with intrathecal methotrexate but the patient was lost to follow up and the outcome is uncertain [
15]. Published reports indicate that these are aggressive tumors, frequently resistant to therapy, and often rapidly fatal.