Fujimoto, Yoshinori

Ishihara, Susumu

Izumi, Haruka

Kato, Motohiro

Kuraishi, Yasunobu

Nagase, Daisuke

Natori, Kazuhiko

Umeda, Masanori

English

PubMed

Springer - Publisher Connector

LETTER TO THE EDITOR
IgD myeloma indicated by plasma cells in the peripheral
blood and massive pleural effusion
Kazuhiko Natori & Haruka Izumi & Daisuke Nagase &
Yoshinori Fujimoto & Susumu Ishihara &
Motohiro Kato & Masanori Umeda & Yasunobu Kuraishi
Received: 18 June 2007 /Accepted: 9 January 2008 / Published online: 12 February 2008
# The Author(s) 2008
Dear Editor,
Multiple myeloma, a B-cell malignancy characterized by
clonal proliferation of plasma cells in the bone marrow, has
been associated with unique clinicopathologic features,
genetic abnormalities, and response to therapy [1–3].
Immunoglobulin D (IgD) myeloma is a rare disease,
accounting for about 2% of all myelomas. Pleural effusions
occur in 6% of myeloma patients. The etiology is
multifactorial and effusions due to pleural myelomatous
involvement are rare, occurring in <1% of the cases [4].
We experienced a patient with IgD 1 multiple myeloma,
which was first indicated by plasma cells in the peripheral
blood. Furthermore, cytogenetic study of the pleural
effusion revealed several abnormalities. We reviewed the
clinical and cytogenetic features of this case and report the
findings in detail.
An 82-year-old man was admitted to our hospital in
February 2002 with the chief complaint of dyspnea on
effort and arrhythmia. His medical history included myo-
cardial infarction in 1991. Chest X-ray results showed
cardiomegaly and bilateral pleural effusion. He was
diagnosed with acute heart failure as a result of previous
myocardial infarction. The administration of diuretics and
an antiarrhythmic resulted in a rapid improvement. How-
ever, the recovery did not last; the pleural effusion slowly
increased and diuretics were ineffective. Moderate anemia
worsened and transfusion was necessary. Hematological
examination revealed plasma cells in the peripheral blood
and a hematologist was consulted. On physical examina-
tion, there was anemia in the connective pulp, and heart
sounds showed a systolic murmur. There was a decrease in
breath sounds at the base of both lungs. Bilateral presidia-
pitting edema was evident. Hematological examination
revealed anemia (hemoglobin 7.7 g/dl) with plasma cells
in the peripheral blood (18%). Total serum protein was
6.0 g/dl with 64.9% albumin and 14.5% γ-globulin.
Creatinine 1.35 mg/dl, blood urea nitrogen 27 mg/dl, uric
acid 13.3 mg/dl, and lactate dehydrogenase 679 IU/L
(reference range 230–460). Immunoelectrophoresis showed
monoclonal IgD (λ) in the serum and Bence Jones protein
(1) in the urine. Quantitative immunoglobulin determina-
tion showed a marked increase in IgD, 934 mg/dl, while
IgG, IgA and IgM levels were decreased (Table 1). Bone
marrow aspiration resulted in dry tap and biopsy results
showed multiple myeloma. Chest X-ray results showed
bilateral pleural effusion, whereas X-ray examination of the
rest of the body was normal. Echocardiography results did
not indicate amyloid deposition in the myocardium, but the
ejection fraction was decreased because of a previous
myocardial infarction.
The patient also underwent thoracentesis. Cytological
examination of the pleural effusion showed numerous
plasma cells. There were two sizes of atypical plasma
cells: small, round-shaped, mature plasma cells, and large,
round-shaped, immature plasma cells. Clusters of differen-
tiation 38 (CD38) and CD138 surface markers were
investigated in the pleural effusion and found to be positive
in 99.4% and 91.5% of the cells, respectively. Metaphase
cytogenetic study on the pleural effusion revealed abnor-
mal karyotypes by G-banding. In the abnormalities, 11q13,
14q32 was evident and +9, −13, −22 were also detected.
After the first cycle of combination chemotherapy with
cyclophosphamide, vincristine, melphalan, predonisone
Ann Hematol (2008) 87:587–589
DOI 10.1007/s00277-008-0444-5
K. Natori (*) :H. Izumi :D. Nagase :Y. Fujimoto : S. Ishihara :
M. Kato :M. Umeda :Y. Kuraishi
Division of Hematology and Oncology, Department of Medicine,
Toho University Medical Center, Oomori Hospital,
6-11-1, Ohmorinishi, Ohta-ku,
Tokyo, Japan
e-mail: natori@med.toho-u.ac.jp
(VCMP)–vincristine, saimerine, Adriamycin, predonisone
(MCNU-VMP; Table 1), the plasma cells in the peripheral
blood disappeared; chest radiograph showed a reduction of
pleural effusion and the anemia improved. IgD levels
decreased rapidly to 44.7 mg/dl after completion of four
cycles of chemotherapy. The patient was discharged from
our hospital in early June. In outpatient clinic, the patient
was treated two more times with the same chemotherapy,
but high fever persisted and bilateral pleural effusions
increased. He was readmitted in late August and treated
with antibiotics and an antifungal agent, but the clinical
course was aggressive, and he died of septic complications
and progression of the disease.
IgD myeloma was first reported in 1965 by Row and
Fahey [5], and the pathological and clinical features were
described by Jancelewicz et al. [6] and Hobbs and Corbett
[7]. IgD myeloma is characterized by a small monoclonal
IgD peak, occurrence in younger subjects, primarily in
men, a high incidence of both Bence Jones proteinuria and
renal insufficiency, an exceptionally high prevalence of 1
light chains over κ light chains, and frequent occurrence of
extraosseous spread. The difficulty in the diagnosis of IgD
myeloma is based on the lack of an M component. IgD
exhibits a very short biological half-life in peripheral blood.
The rate of catabolism of IgD is 26% per day, compared
with 3~6% per day for IgG, and 10~15% per day for IgA.
Myelomatous pleural effusion has been considered as a
late manifestation in the natural history of multiple
myeloma or as an expression of the aggressive behavior
of the disease. Pleural effusions occur in approximately 6%
of patients with myeloma. The etiology is multifactorial,
and effusions due to pleural myelomatous involvement are
rare, occurring in <1% of the cases [4]. In previous reports
of myelomatous pleural effusions, 80% were due to IgA,
whereas the others were mostly due to IgG.
Pleural effusions in myeloma may be due to nephrotic
syndrome, pulmonary embolism, congestive heart failure
secondary to amyloidosis, secondary neoplasms and infil-
tration of myeloma cells from adjacent skeletal or paren-
chymal locations, direct implantation of plasma cells on the
pleura, and mediastinal lymph node infiltration with
lymphatic obstruction [8–10]. Extramedullary plasmacy-
toma is a rare type of tumor, comprising approximately 4%
to 6% of the plasma cell malignancies [8, 11].
Table 1 Laboratory findings
Blood picture Blood chemistry Immunoglobulin Coagulation work Pleural fluid
RBC 224×104 per microliter CRP 0.2 μg/dl BUN 27.0 mg/dl IgG 373 mg/dl PT 13.3 s Surface marker
Hb 7.7 g/dl Na 143 mM Cr 1.35 mg/dl IgA 33 mg/dl APTT 35.4 s CD19 0.7%
Hct 23.4% Cl 11 mM UA 13.3 mg/dl IgM 10 mg/dl Fbg 375 mg/dl CD20 0.6%
MCV 105.0 μm3 K 4.2 mM GOT 32 IU/l IgD 934 mg/dl FDP 2.0 μg/dl CD27 3.0%
MCH 34.5 pg Ca 9.1 mg/dl GPT 29 IU/l CD83 99.4%
MCHC 33.0% P 4.7 mg/dl γ-GTP 62 IU/l CD138 91.5%
PLT 5.7×104 per microliter TP 6.0 g/dl ChE 217 IU/l Chromosome analysis
WBC 4,000 per microliter Alb 64.90% LDH 679 IU/l 47,XY,del(1)del(1)
(p11p13)ins(1;?)
(q21:?),add(3)(p13)(,
−8,+9),
Eos 5.0% α 1-gl 3.70% ALP 241 IU/l t(11;14)(q13;q32),add
(12)(p11),−15add(17)
(p11),−22,+mar (ten
cells)
Seg 28.0 α2-g l 9.10% 47,idem,add(3)(p11)
(nine cells)
Lym 39.0 β-g l 7.80% 46,idem,−9,−13,−21,
−22,+3mar (one cell)
Aty. Lym 17.0 γ-g l 14.50% IL-6 3,970 pg/ml
Mono 10.0
588 Ann Hematol (2008) 87:587–589
In our case, a variety of chromosomal abnormalities
were detected from the pleural effusion. Translocations
involving the immunoglobulin heavy chain (IgH) region at
chromosome region 14q32 are regularly involved in human
B-cell malignancies and may upregulate existing oncogenes
or create new hybrid genes with transforming properties.
For example, Burkitt lymphoma shows a specific t(8;14)
(q24;q32). This case demonstrated t(11;14)(q13;q32),
which commonly results in the fusion of the BCL-1 locus,
although the break points in myeloma may be different
from those observed in mantle cell lymphoma. The
protooncogene c-myc is translocated to the IgH locus at
14q32, resulting in increased expression of the oncogene
because of strong immunoglobulin enhancers [12]. 14q32
has been detected in 74% of patients with multiple
myeloma, by fluorescence in situ hybridization, and in
85% of plasma cell leukemia cases [2]. 14q32 is one of the
factors related to a poor prognosis. These translocations are
found in the earliest stage of the disease, suggesting that
such translocations are an early and possibly initiating
event in the disease development [13]. The detection of
genetic changes is important, not only because of their
association with clinical prognosis, but also because they
can be used as measurable targets for response to treatment.
Malignant effusions can occur in the terminal stage of
the disease and are difficult to treat. This particular case of
multiple myeloma had a poor prognosis and required
appropriate therapy. In general, with the appearance of
malignant effusions, systemic chemotherapy and drainage
are necessary. In IgD myeloma, most patients tend to be
younger than other myeloma patients, and there are likely a
large number of eligible cases. As a therapeutic approach
for IgD myeloma, especially the 1 type, we consider that
peripheral blood stem cell transplantation will result in a
good prognosis after conventional chemotherapy.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
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Ann Hematol (2008) 87:587–589 589


IgD myeloma indicated by plasma cells in the peripheral blood and massive pleural effusion

Kazuhiko Natori

Haruka Izumi

Daisuke Nagase

Yoshinori Fujimoto

Susumu Ishihara

Motohiro Kato

Masanori Umeda

Yasunobu Kuraishi

A new human immunoglobulins; I. A unique myeloma protein.

Chromosome translocations in multiple myeloma.

Co-incidental presentation of IgA λ multiple myeloma and pleural involvement with IgM κ non-Hodgkin’s lymphoma.

IgD multiple myeloma. Review of 133 cases.

Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and presentation.

Pleural effusion as the first sign of extramedullary plasmacytoma.

Pleural effusion in multiple myeloma.

The role of immunoglobulin translocation in the pathogenesis of B-cell malignancies.

Thoracic and pulmonary abnormalities in multiple myeloma.

Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas.

Younger age of presentation and extraosseous tumor in IgD myelomasis.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2413089

IgD myeloma indicated by plasma cells in the peripheral blood and massive pleural effusion

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