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