Case report

A 70-year-old patient initially consulted his general physician because of a persisting anal abscess that did not respond to a two-week antibiotic treatment with amoxicillin and clavulanic acid. A blood test to assess the patient’s response to this infection, unexpectedly showed thrombocytopenia, macrocytic anemia and a normal white blood cell count with a leukoerythroblastic presentation (Table 1 and Figure 1A). Therefore, the patient was referred to the emergency department for further examination. Careful anamnesis revealed extensive weight loss (± 20 kg) during the last couple of months, increasing fatigue, decreased exercise tolerance and right hypochondrial discomfort. Additionally, the patient reported no night sweats. Further physical examination revealed hepatomegaly, which was later confirmed by ultrasound examination. No lymphadenopathy nor other physical irregularities could be observed. The patient’s medical history included hypercholesterolemia and poorly controlled type 2 diabetes. His previous blood test, performed three months earlier, did not show any hematological abnormalities (Table 1 ) as well as a negative HIV status. Based on these preliminary findings, the initial differential diagnosis included acute leukemia, myelodysplastic syndrome (MDS) and myelofibrosis.
An examination of a bone marrow smear and trephine biopsy from the iliac crest was performed. The aspirate was stained with Wright-Giemsa for cytomorphologic evaluation and showed a markedly decreased megakaryo-, erythro- and myelopoiesis as well as the presence of a large population of blasts (75%) with a pleomorphic morphology. These cells displayed a moderate nuclear-to-cytoplasmic ratio, one or more prominent nucleoli and a rim of basophilic cytoplasm. Although the morphology of most of these cells was compatible with monoblasts (50%) (Figure 1B ), some cells displayed a perinuclear halo zone (25%) (Figure 1C ), more reminiscent of plasmablasts. Due to the peculiar morphologic presentation of the blastic cells, the differential diagnosis was adjusted to the following entities: plasmablastic myeloma, plasmablastic lymphoma, plasma cell leukemia, and acute leukemia. Plasma cell leukemia was excluded since only 2% plasma cells were detected by flow cytometry, far below the 20% diagnostic criterium. Other laboratory findings (Table 1 ) included a mildly increased lactate dehydrogenase (LDH) and C-reactive protein (CRP), no significant hypercalcemia, a normal kidney function and a markedly elevated β2-microglobulin level. IgG and IgA levels were mildly decreased whilst IgM was not detectable. Serum free light chains were within normal values and displayed a normal κ/λ ratio. Moreover, serum electrophoresis and immunofixation could not detect a monoclonal fraction of IgG, IgA, IgM, IgD, IgE, kappa or lambda. The latter experiments were repeated at 37°C to exclude precipitation of cryoglobulins, as well as with β-mercaptoethanol pretreatment to rule out polymerization of a monoclonal M-protein; all yielding the same result.
Flow cytometry was performed according to the EuroFlow protocols (Euroflow.org) to distinguish acute leukemia from a plasma cell neoplasm.1 The acute leukemia orientation tube (see details at euroflow.org) showed a large population with a distinctive high forward scatter (FSC) without a blastic phenotype: CD45-, CD19dim, CD34-, myeloperoxidase (MPO)-, cytoplasmic CD3-, cytoplasmic CD79a- and CD7-. Subsequently, the plasma cell disorder panel confirmed the presence of neoplastic cells with a typical plasma cell immunophenotype: CD45-, CD19dim, CD38bright, CD138+, CD28-, and CD56-. Interestingly, no cytoplasmic or surface light chain expression could be demonstrated in two independent analyses. Lack of CD56 expression along with the forward scatter properties allowed us to exclude a blastic plasmacytoid dendritic cell neoplasm.
Microscopic evaluation of the bone marrow trephine biopsy showed a limited presence of the three lineages and a striking invasion of neoplastic cells with plasmablastic aspect (Figure 2A ). The reticulin staining corresponded to a myelofibrosis grade 1. Immunohistochemistry (IHC) confirmed bone marrow invasion by CD38+ and CD138+ neoplastic cells (Figure 2B ). Additional staining showed MUM1 and cyclin D1 expression and absence of pan-B markers (PAX5, CD79a and CD20). Analogous to flow cytometry, no kappa or lambda expression could be demonstrated. IHC staining of IgG, IgA and IgM showed no clear positive expression, with the exception of a weak reaction, possibly aspecific, for IgG in combination with a high background staining. The weak IgG expression at diagnosis was confirmed in a second trephine biopsy in follow-up. Other analyzed markers (HHV-8, LMP-1 and MYC) were negative. Chromogenic in situ hybridization or EBV-encoded RNA transcript (EBER) could not be performed since only decalcified material was available.
G-banding analysis showed a complex karyotype. Fluorescence in situ hybridization (FISH) was performed on CD138 isolated cells and revealed the presence of a t(11;14)(q13;q32) without evidence for the presence of t(4;14), t(14;16) or MLL rearrangements. Shallow whole genome sequencing, also performed on DNA from CD138 isolated cells, showed the presence of segmental copy number gains and losses, as well as numerical chromosome aberrations. Multiplex polymerase chain reaction showed a clonal signal for the IgH and IgK light chains, thereby confirming the presence of a clonal B-cell neoplasm. The t(11;14)(q13;q32) translocation is commonly observed in plasmablastic myeloma, whereas plasmablastic lymphoma is typically associated with a MYC-rearrangement.
PET-CT was compatible with the presentation of a disseminated myeloma invasion showing a diffuse invasion pattern of the bone marrow with multiple osteolytic lesions, without any extranodal localizations.
Although there are no definite criteria to differentiate non-secretor plasmablastic myeloma from plasmablastic lymphoma, this case is most compatible with a non-secretor myeloma based on the clinical presentation, disseminated bone marrow involvement and lytic lesions without extranodal involvement, along with extensive laboratory investigations.
The patient was treated with a combination of velcade, endoxan and dexamethasone (VCD) and further antibiotic treatment was sufficient to cure the anal abscess.2 After two VCD cycles, the bone marrow biopsy revealed a drop in plasmablastic cells from 75% to 15% and PET-CT showed one residual metabolically active region in the right 4th rib. Two additional VCD cycles were given and evaluation of a bone marrow biopsy showed a slightly elevated plasma cell count (5-10%) with atypical morphology. Despite the poor prognosis, the patient has a very good partial response (VGPR) after four VCD cycles and an autologous stem cell transplant is planned in the near future. The patient gave an informed consent for this case report.