Discussion

This case demonstrates how challenging a correct interpretation of a bone marrow aspirate is when pleomorphic plasmablasts are present. Definite distinction between plasmablastic lymphoma and plasmablastic myeloma is difficult due to overlapping morphological and immunophenotypical features and the lack of distinctive immunophenotypic criteria.
Plasmablastic lymphoma was first described in 1997 by Delecluse et al. as an aggressive lymphoma with neoplastic cells that have immunoblastic or plasmablastic appearance. Plasmablastic lymphoma predominantly occurs in patients with preexisting immunodeficiency, typically HIV, and is frequently located in extranodal sites, mainly the head and neck region or the gastrointestinal tract.3,4Later publications also described cases in immunocompetent patients.5,6 The clinical image can mimic the characteristic presentation of a plasma cell myeloma with the presence of an M-protein but a disseminated stage with bone marrow involvement is rarely seen at presentation.5,7,8,9 Although plasmablastic lymphoma and plasmablastic myeloma show common features, a clear diagnosis is important because these two different disorders require different therapeutic protocols.10 The presence of an immunodeficiency or a positive EBER can be useful in the differential diagnosis. EBER is positive in 60 – 75% of the plasmablastic lymphoma cases whereas latent membrane protein 1 (LMP1) is rarely expressed.11,12 The immunophenotype of plasmablastic lymphoma consists of a characteristic plasma cell phenotype including CD138, CD38 and MUM1 positivity. Cytoplasmic immunoglobulins are commonly expressed, mostly IgG with either kappa or lambda light chain. Finally, some cases also express CD45, CD56, CD10 and CD79a while cyclin D1 and B-cell markers (CD20 and PAX5) are usually negative.7,9,11,13,13
In contrast to the patient in this case report, the majority of plasmablastic lymphoma cases that resemble the clinical features of plasma cell myeloma have an HIV infection or suffer from another immunodeficiency. Secondly, the plasmablasts in this case have a plasma cell immunophenoytype but are negative for CD45, CD79a and CD56 which can be present, but not necessarily, in plasmablastic lymphoma. Interestingly, the production of a monoclonal immunoglobulin was only detected by intracellular IHC IgG staining. This intracellular IgG staining was only dimly positive in the bone marrow trephine biopsy at diagnosis and later confirmed in the first follow-up biopsy. The lack of cytoplasmic light chain expression, both by flow cytometry and IHC, supports a defective immunoglobulin light chain production. The absence of cytoplasmic heavy or light chain expression has never been reported in plasmablastic lymphoma but can be observed in plasma cell myeloma variants.14 Approximately 1-3% of the plasma cell myelomas belong to a non-secretor subtype and do not have detectable M-protein in serum.15 A distinction is made within non-secretor plasma cell myeloma variants between a defect in the secretion of a monoclonal Ig, i.e. non-secretor myeloma (85%), and a defect in the production, i.e. non-producer myeloma (15%). In the latter, no cytoplasmic heavy and light chains are detected.16,17 The clinical presentation of a non-secretor plasma cell myeloma, including the non-producer variant, is similar to plasma cell myeloma except for a lower incidence of renal insufficiency due to the absence of an M-protein, which is applicable in this case. The prognosis of plasma cell myeloma variants is similar to other types of plasma cell myeloma.15 The t(11;14)(q13;q32) and a complex karyotype are commonly detected in plasma cell myeloma but are also, although less frequently, described in plasmablastic lymphoma with HIV.17,18 According to the genetic Mayo stratification, our patient has a standard risk based on the presence of a t(11;14).19 Unfavorable risk indicators in this case are, as stated by the international staging system, a high serum β2-microglobin level and a plasmablastic morphology, which underlines the impact of morphologic evaluation.20,21 The latter is also highlighted in a recent case report of an aggressive presentation of a pleomorphic plasmablastic myeloma with the presence of an M-protein.22