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Journal of Community Hospital Internal Medicine
Perspectives
ISSN: (Print) 2000-9666 (Online) Journal homepage: http://www.tandfonline.com/loi/zjch20
An unusual case of chronic lymphocytic leukemia,
multiple myeloma and cardiac amyloidosis
Dongyan Liu, Hakim T. Uqdah & Alisha D. Gordy
To cite this article: Dongyan Liu, Hakim T. Uqdah & Alisha D. Gordy (2017) An unusual case of
chronic lymphocytic leukemia, multiple myeloma and cardiac amyloidosis, Journal of Community
Hospital Internal Medicine Perspectives, 7:4, 230-233, DOI: 10.1080/20009666.2017.1370940
To link to this article: http://dx.doi.org/10.1080/20009666.2017.1370940
© 2017 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group.
Published online: 19 Sep 2017.
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CASE REPORT
An unusual case of chronic lymphocytic leukemia, multiple myeloma and
cardiac amyloidosis
Dongyan Liu
a
, Hakim T. Uqdah
a
and Alisha D. Gordy
b
a
Department of Medicine, Greater Baltimore Medical Center, Towson, MD, USA;
b
Department of Pathology, the Johns Hopkins Hospital,
Baltimore, MD, USA
ABSTRACT
Light chain amyloidosis has very rarely been reported in association with chronic
lymphocytic leukemia (CLL). We reported on a 76-years-old female who presented
with simultaneous kappa-restricted chronic lymphocytic leukemia (CLL) and a lambda-
restricted multiple myeloma with plasma cells causing AL amyloidosis involving the
heart. While monoclonal immunoglobulins occasionallyproduced by CLL have previously
been implicated in AL amyloidosis, there only a few cases reported of AL amyloidosis
resulting from a distinct plasma cell dyscrasia that is not clonally related to the con-
current CLL.
ARTICLE HISTORY
Received 6 April 2017
Accepted 7 August 2017
KEYWORDS
Chronic lymphocytic
leukemia; amyloidosis; free
light chain; multiple
myeloma; echocardiography
1. Introduction
Chronic lymphocytic leukemia (CLL) is often diag-
nosed at an early stage by the discovery of lympho-
cytosis on a routine blood cells count. In CLL,
routine serum electrophoresis detects monoclonal Ig
in only less than 5% of cases [1], which may cause
glomerulonephritis or other paraneoplastic phenom-
ena [2]. Immunoglobulin light chain amyloidosis
(AL) is characterized by the progressive deposition
of immunoglobulin light chains, leading to organ-
wide amyloid fibril deposits and organ dysfunction.
Light chain amyloidosis may be under-recognized in
association with chronic lymphocytic leukemia (CLL)
or small lymphocytic lymphoma (SLL).
2. Case report
A 76-years-old Caucasian female with CLL (diag-
nosed five years ago with stable high lymphocyte
count) and non-ischemic cardiomyopathy pre-
sented with worsening dyspnea on exertion. One
year earlier she presented with dyspnea on exertion
and mild bilateral lower extremity edema. Her
initial EF was 50% by echocardiogram and her
left heart catheterization did not show any evidence
of coronary artery disease. A month prior to
admission she developed progressive dyspnea with
exertion and worsening lower extremity edema. At
thattimeshealsowasfoundtohaveanEFof25%
(decreased from 50%) and hyponatremia. Her
regimes of diuretics, beta-blocker, and ACEI were
further optimized.
On admission, she was found to have borderline
blood pressure (103/60 mmHg), and bilateral lower
extremity edema. Upon further previous chart review,
she had a persistent elevated serum free lambda light
chain of about 870–1000 mg/L and faint lambda light
chain monoclonal protein on SPEP (54–118 mg/dL)
over the last 18 months. At this admission, the white
blood cell count was 27.4 × 10
9
/L with 70% lympho-
cytes (same range as her baseline). The red blood cell
count was 3.90 × 10
12
/L, and the platelet count was
188 × 10
9
/L. She also had worsening hyponatremia
(sodium of 123 meq/L, baseline 130–133 meq/L).
Creatinine was 1.2 mg/dL (baseline 1.0–1.2) and
urine analysis was negative for protein.
SPEP and immunofixation analysis revealed
lambda free light chain (Bence Jones) proteinemia
and hypogammaglobulinemia involving IgG and
IgA. Serum free lambda light chain was 724 mg/L,
and kappa/lambda ratio was 0.01, indicating over-
production of lambda light chain. UPEP showed a
spike in the beta region, 888.7 mg/24h. EKG was low
voltage and CXR revealed bilateral small pleural effu-
sion. Trans-thoracic echocardiogram (TTE) revealed
normal left ventricular wall thickness, severe global
systolic hypokinesis of the left ventricle, EF 25%, an
inter-ventricular diastolic septal thickness of 8.0 mm,
moderate right atria dilation and moderate low gra-
dient aortic stenosis.
A right heart catheterization was performed
revealing elevated right and left heart filling pres-
sures(RA17mmHg,PA55/28mmHg(mean
38 mmHg), PCW 28 mmHg). Cardiac index was
CONTACT Dongyan Liu dliu@gbmc.org Department of Medicine, Greater Baltimore Medical Center, Towson, MD, USA
JOURNAL OF COMMUNITY HOSPITAL INTERNAL MEDICINE PERSPECTIVES, 2017
VOL. 7, NO. 4, 230–233
https://doi.org/10.1080/20009666.2017.1370940
© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/),
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low at 1.53 L/min/m
2
. Endo-myocardial biopsy
showed focal patchy infiltration of the myocardium
and fibrous tissue with Congo red stain positive for
amyloid (Figure 1).
Bone marrow biopsy revealed hypercellular marrow
that was replaced by nodules of small lymphocytes
and patchy sheets of plasma cells. Plasma cells
comprise approximately 50% of the cellularity.
Immunohistochemistry stains highlighted the plasma
cells that were lambda light chain-restricted. Flow cyto-
metry showed 63% monoclonal B-cells that express CD5
and kappa light chain-restricted as well as clonal plasma
cells that express lambda light chain, demonstrating that
she had two separate clones. A Congo red stain did not
show definitive amyloid deposition (Figure 2).
Patient’s home medications of beta-blocker and
ACE inhibitor were discontinued. She was treated
with furosemide intravenously and her weight
decreased to 48.4 kg from 50.5 kg. Patient was main-
tained on furosemide and spironolactone with plans
for chemotherapy. However, she was readmitted for
refractory heart failure symptoms requiring inotropic
support. Ultimately, she chose a palliative approach.
3. Discussion
Immunoglobulin light chain (AL) amyloidosis is a
systemic disorder characterized by widespread
deposition of amyloid fibrils derived from monoclo-
nal immunoglobulin light chains in organs and soft
Figure 1. Deposition of amyloid in the myocardium. a–b The amyloid deposits display characteristic apple-green birefringence
by polarized light microscopy (Congo red stain 100X). c (hematoxylin-eosin stain 100X) and d (Masson trichrome stain 100X)
shows the amyloid deposit in the myocardium.
Figure 2. a–b Bone marrow with dense aggregates of plasma cells consistent with multiple myeloma. (a hematoxylin-eosin
stain 100X; b 200X). c–d Immuno-histochemical staining of CD138 positive plasma cells comprising 50% of marrow cellularity.
CD138 (syndecan-1) was found to be a specific marker for plasma cells. (c 100X; d 200X).e–f Stain for kappa light chain was
negative (e 100X; f 200X). g–h stain for lambda light chain was positive (g 100X; h 200X).
JOURNAL OF COMMUNITY HOSPITAL INTERNAL MEDICINE PERSPECTIVES 231
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tissues. AL is typically caused by an underlying
plasma cell clone disorder and occurs in 6–15% of
patients with multiple myeloma [3]. Both light chain
amyloidosis (AL) and non-AL amyloidosis have
rarely been reported in association with chronic lym-
phocytic leukemia (CLL) or small lymphocytic lym-
phoma (SLL) [4].
In CLL, monoclonal light chains are detected in
the serum, and the surfaces of lymphocytes and glo-
meruli are predominantly kappa type, which is much
less predisposed to form the β-pleated sheet structure.
Lambda light chains are more amyloidogenic than
kappa light chains, resulting in lambda AL being
twice as common as kappa AL [5]. Serum free light
chain (FLC) levels are usually low in CLL patients.
The predominant kappa presentation and low level of
FLC explain why there are up to one-third of CLL
patients who have abnormal serum FLC ratios, but
rarely have reported systemic amyloidosis [6].
Another known observation is that in CLL/SLL
lymph nodes and bone marrow, polyclonal B-cells
share the same micro-environmental interactions as
CLL tumor cells [6]. CLL cells producing clonally
restricted FLCs coexist with lymphocytes expressing
non-clonal FLCs in lymph nodes and bone marrow
[6]. This ongoing B-cell activation, which is demon-
strated by the overproduction of polyclonal FLC,
indicates the pathogenesis of several inflammatory
and autoimmune conditions, which are associated
with an increased risk of malignancy transformation
[7]. CLL may function as a cofactor in the neighbor-
hood of B-cells generating light chains and predis-
posing for transformation to multiple myeloma. The
Mayo clinic case series study revealed that in CLL
patients, AL amyloidosis is more commonly caused
by a coexisting plasma cell clone (14 cases out of 18
cases of AL). Among these 14 patients, six had both a
plasma cell clone and a CLL clone that shared the
same light chain. These cases of AL amyloidosis were
almost equally divided between kappa and lambda
restriction [4].
For amyloidosis, the most commonly affected
organs that result in symptoms are the heart, kidney,
skin, peripheral nerves and liver. The most common
presentations of heart are normal ejection fraction
with diastolic dysfunction, and left ventricular hyper-
trophy with low voltage EKG [5].
Evaluation of cardiac involvement is very impor-
tant since the major determinant of outcome in amy-
loidosis is the extent of cardiac involvement. Cardiac
biomarkers, such as natriuretic peptides, particularly
N-terminal pro-B-type natriuretic peptide (NT-pro
BNP) and cardiac troponin-T, play a role for the
assessment of prognosis in AL amyloidosis [8,9].
Echocardiography is one of the main diagnostic
modalities used in patients with suspected cardiomyopa-
thy, including cardiac involvement in AL amyloidosis.
Recent studies showed that tissue Doppler imaging
(TDI)-derived myocardial systolic strain is associated
with overall prognosis in AL amyloidosis. Increased left
ventricular (LV) wall thickness and decreased fractional
shortening, a granular sparkling appearance, longitudinal
left ventricular (LV) function, diastolic relaxation
abnormalities and right ventricular dysfunction with
valvular thickening have all been shown to be associated
with prognosis [10–12].
4. Conclusion
This unusual patient presented with clonally unre-
lated CLL and multiple myeloma plasma cells, the
latter causing AL amyloidosis. It becomes challenging
to diagnose multiple myeloma and other plasma cell
disorders in the setting of CLL and other chronic
leukemias. Clinicians must pay attention to subtle
clinical and laboratory abnormalities to support
further diagnostic testing.
Disclosure statement
No potential conflict of interest was reported by the
authors.
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