Cardiac Lymphoma and Pericardial Effusion in an
American Bulldog
Melisa Rosenthal
Clinical Advisor: Dr. Bruce Kornreich
Basic Science Advisor: Dr. Tracy Stokol
Senior Seminar Paper
Cornell University College of Veterinary Medicine
March 26, 2014
Keywords: cardiac lymphoma, pericardial effusion, cardiac tamponade, flow cytometry, cardiac
mass
1
ABSTRACT
A nine year-old, male castrated, American Bulldog presented to the Cornell University Hospital
for Animals Cardiology Service for abdominal distension and suspected congestive heart failure.
The patient had a nine-day history of progressive polyuria, polydipsia, abdominal distension,
lethargy, inappetance, and increased respiratory effort. An echocardiogram revealed marked
pericardial effusion, cardiac tamponade, a mass in the free wall at the right atrioventricular
junction, and a suspected mass in the ascending aorta. Pericardiocentesis was performed and
cytologic analysis of the fluid revealed large round cells. Flow cytometric analysis of the
pericardial fluid supported a diagnosis of T cell lymphoma. The patient was discharged
following pericardiocentesis and a full resolution of clinical signs was reported five days later.
This report discusses the diagnostic tools utilized in the evaluation of this patient and provides an
overview of cardiac lymphoma, a rare condition in dogs.
CASE HISTORY
A nine year-old, male castrated, American Bulldog presented to the Cornell University
Hospital for Animals (CUHA) Cardiology Service for abdominal distension and suspected
congestive heart failure. The patient had a nine day history of sudden-onset polyuria and
polydipsia and a seven day history of abdominal distension and lethargy.
Five days prior to presentation, the patient was seen by the primary veterinarian. A
complete blood count (CBC) did not reveal any significant abnormalities and a serum chemistry
panel revealed mildly increased alanine aminotransferase (129 U/L, reference interval, 0-100
U/L), increased alkaline phosphatase (408 U/L, reference interval, 0-175 U/L), mild
hyperglycemia (140 mg/dL, reference interval, 70-130 mg/dL), mild hypoproteinemia (5.6 g/dL,
2
reference interval, 6.0-7.8 g/dL) with low normal albumin (2.8 g/dL, reference interval, 2.7-3.8
g/dL), and mild hyperphosphatemia (6.3 mg/dL, reference interval, 3.0-6.0 mg/dL). These
findings are consistent with hepatic injury likely from congestion secondary to congestive heart
failure, endogenous stress, and possibly prolonged inappetance. A urinalysis revealed low urine
specific gravity (1.007), moderate bilirubin and protein, and few granular casts. The excessive
bilirubinuria for the urine specific gravity may be related to cholestasis secondary to suspected
hepatic congestion. The proteinuria with the granular casts and low urine specific gravity
suggests a degree of renal tubular injury (cause unknown), although medullary solute washout
from polyuria may be contributing to the low specific gravity. Further investigation of renal
disease was not performed in this patient given the severity of his cardiac disease. A vectorborne disease screening test (SNAP® 4Dx®) was negative for Borrelia burgorferi, Anaplasma
phagocytophilum, Ehrlichia canis, and Dirofilaria immitis. Thoracic radiographs revealed
globoid cardiomegaly and an enlarged caudal vena cava, and abdominal radiographs revealed
decreased serosal detail consistent with peritoneal effusion and mild hepatomegaly (Figure 1).
Abdominocentesis yielded two liters of straw-colored peritoneal effusion and cytologic analysis
of the fluid revealed a high protein transudate with a total protein of 5.1 g/dL and a nucleated cell
count of 1.3 thousand/uL. The cell population consisted of a mixture of neutrophils and
macrophages, low numbers of small lymphocytes, and few clusters of mesothelial cells. No
infectious agents or neoplastic cells were seen.
Within several days of the abdominocentesis, the patient’s clinical signs returned with
progressively worsening abdominal distension, lethargy, inappetance, and sporadically increased
respiratory effort. Based on a clinical suspicion of right-sided congestive heart failure, the
patient was referred to the CUHA Cardiology Service.
3
B
A
D
C
Figure 1: Thoracic and
Abdominal Radiographs.
(A) Right lateral and (B)
ventrodorsal views of the
thorax demonstrating a
globoid cardiac silhouette
and dilated caudal vena
cava. (C) Right lateral and
(D) ventrodorsal views of
the abdomen showing
abdominal effusion and
hepatomegaly.
CLINICAL PRESENTATION
On presentation, the patient was quiet, alert, and responsive. Due to the patient’s
temperament, a limited physical examination was performed. The dog was tachycardic (heart
rate of 140 beats per minute) and panting with increased respiratory effort when positioned in
sternal recumbency. The heart sounds were muffled on auscultation and femoral pulses were
weak bilaterally. The abdomen was distended with a palpable fluid wave. Several small, soft,
subcutaneous masses were palpable over the trunk of the patient and a large scar was seen on the
left caudal cranium. No other significant abnormalities were found on limited physical
examination.
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PROBLEM LIST AND DIFFERENTIAL DIAGNOSES
The patient’s problem list included the following: tachycardia, muffled heart sounds,
weak pulses, tachypnea, increased respiratory effort, cardiomegaly, abdominal effusion,
hepatomegaly, increased liver enzymes, polyuria, polydipsia, lethargy, and inappetance. The
globoid cardiomegaly, muffled heart sounds, tachycardia, and weak pulses were consistent with
pericardial effusion causing cardiac tamponade. The main differential diagnoses for these
findings were cardiac neoplasia, particularly hemangiosarcoma, and idiopathic pericarditis.
Other differential diagnoses for pericardial effusion include infectious pericarditis, congestive
heart failure, hemorrhage due to trauma or coagulopathy, and uremic pericarditis. Given the lack
of a supportive history of penetrating trauma, other evidence of coagulopathy, and the rarity and
lack of available data supportive of the other causes of pericardial effusion in dogs, the primary
differential diagnoses for this patient’s disease were idiopathic or neoplastic pericardial effusion.
The remainder of the patient’s clinical signs could be attributed to pericardial effusion
and cardiac tamponade. The venous congestion associated with right-sided congestive heart
failure could also explain the enlarged caudal vena cava, hepatomegaly, and elevated liver
enzymes. Other differential diagnoses for hepatomegaly and increased liver enzymes include
neoplastic infiltration of the liver, endocrine disease (diabetes mellitus or hyperadrenocorticism),
or chronic active hepatitis. The increased respiratory effort was consistent with discomfort due
to abdominal distension and other respiratory pathology was not suspected due to the resolution
of increased effort when the patient was standing and the lack of pulmonary pathology on
thoracic radiographs. The polyuria and polydipsia were consistent with intravascular volume
contraction secondary to third spacing of fluids as well as the activation of the renin-angiotensinaldosterone system (RAAS) that is seen with congestive heart failure [1].
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DIAGNOSTIC PROCEDURES
An electrocardiogram was performed and revealed a normal sinus rhythm at 140 beats
per minute with a normal mean electrical axis of 60 degrees and mild electrical alternans (Figure
2). Echocardiography revealed severe pericardial effusion with cardiac tamponade (Figure 3). A
roughly 1.7 cm by 1.4 cm diameter mass effect was seen in the right free wall at the
atrioventricular junction. This structure was cavitated and of mixed echogenicity (Figure 3). A
hyperechoic space-occupying lesion was also seen on the anterior aspect of the ascending aorta
that measured 1.3 cm by 4.5 cm (Figure 3). This lesion could be consistent with a second mass
or organized fibrin accumulation. During the echocardiogram, the patient had an episode of
collapse with minimal to no loss of consciousness. The patient was sedated with butorphanol
(0.25mg/kg) and dexmedetomidine (1µg/kg) administered intramuscularly and placed in left
lateral recumbency. A small area on the right thorax was clipped and prepped in standard aseptic
fashion and a 16-gauge catheter was introduced into the pericardial space. Approximately 650
ml of serosanguinous fluid was removed from the pericardium and a liter of Plasmalyte-A was
given as a bolus during the procedure. Following pericardiocentesis, the echocardiogram was
repeated and revealed a small amount of residual pericardial effusion with no cardiac tamponade
(Figure 3). Post-pericardiocentesis measurements included a normal fractional shortening
(47.5%) and ejection fraction (68.3%) and an increased left atrium to aorta size ratio (1.76). The
enlargement of the left atrium was suspected to be due to the bolus of fluids given during
pericardiocentesis.
The pericardial fluid obtained from pericardiocentesis was submitted for fluid analysis
and cytologic assesment. It was described as a dark red, opaque fluid and had an increased total
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protein of 4.2 g/dL and a high nucleated cell count of 20.4 thou/uL. The packed cell volume was
27%. A differential cell count showed a population of large round cells making up 69% of the
nucleated cells in the sample, with 20% neutrophils, 6% small lymphocytes, and 5%
macrophages making up the majority of the remaining cells. On cytologic examination, the large
round cells were described as having fine chromatin, indistinct nucleoli, clear cytoplasmic
granules, and bizarre mitotic figures (Figure 4). A cytologic diagnosis of a neoplastic and
hemorrhagic effusion was made, with the main differential diagnoses of lymphoma. Given the
suspicion of lymphoma, flow cytometric analysis was performed on the pericardial fluid.
Analysis of a gate containing the abnormal round cells showed a positive reaction with
antibodies against markers for leukocytes (CD45, CD18) and T cells (CD3, CD90) (Figure 5).
These results indicated a T cell lymphoma with aberrant lack of expression of MHCII, CD5,
TCRαβ, and CD4 or CD8 (Figure 5).
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Figure 2: Electrocardiogram. Six-lead electrocardiogram demonstrating mild
electrical alternans.
B
A
*
*
C
D
Figure 3: Echocardiogram. (A) Long axis view demonstrating mass in free wall
near right atrioventricular junction (arrow). (B) Hyperechoic lesion on ascending
aorta (arrow). (C) Long axis view demonstrating pericardial effusion (*). (D)
Long axis view post-pericardiocentesis showing that most of the pericardial fluid
has been removed from the pericardial space (*).
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A
B
Figure 4: Pericardial Fluid Cytology. High magnification (500x in A and 1000x in B)
images of the pericardial effusion demonstrating large round cells with fine chromatin,
cytoplasmic vacuoles, mitotic figures (arrow, A), and indistinct nucleoli.
A
B
C
Figure 5: Flow Cytometric Analysis. (A) Flow cytometric dotplot showing distribution
of cells within the pericardial fluid sample. R1 indicates the gate containing normal small
lymphocytes. R2 contains the large abnormal cells as well as some background
monocytes and neutrophils. (B) Histograms showing fluorescent tagging of marker
expression by the cells in gate R2, demonstrating positive expression of CD3, CD45, and
CD18. (C) Histograms of the cells in gate R2, demonstrating that the cells are negative
the markers MHC II, TCRαβ, and CD5.
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TREATMENT AND OUTCOME
Following pericardiocentesis, the patient was monitored in the intensive care unit during
the day before being discharged. The dog was discharged with instructions for the owners to
measure the circumference of the dog’s abdomen and heart rate daily to monitor for resolution of
ascites or return of pericardial effusion. Two days following discharge from the hospital, the
owners reported that the abdominal girth had decreased in size and the inappetance had resolved.
Five days after discharge, the owners reported that the clinical signs had resolved completely
with no noticeable abdominal distension or respiratory effort and improved appetite and energy
levels.
One month following presentation to the Cardiology Service, the patient was seen by the
CUHA Oncology Service in order to discuss further treatment options for the cardiac lymphoma.
At that time, the patient was reportedly doing well at home with only one episode of lethargy
reported one week prior to presentation. During that episode, the patient had been seen by an
emergency veterinarian, who determined that there was no pericardial effusion and only scant
peritoneal effusion. The dog recovered from the lethargy without treatment. On presentation to
the Oncology service, a limited physical examination did not reveal any significant findings apart
from a superficial skin infection on the lateral neck. Staging tests including thoracic radiographs,
abdominal ultrasonographic examination, complete blood count, chemistry, urinalysis, and bone
marrow aspiration were recommended to the owners and treatment with chemotherapy or
palliative prednisone were discussed. The owners elected not the treat the dog at that time, and
the patient was discharged with cephalexin for the dermatitis appreciated on physical exam.
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DISCUSSION
Cardiac neoplasia is a relatively rare cause of illness in dogs, with a reported incidence of
0.19% in a population of dogs presenting to veterinary hospitals [2]. Of these cardiac tumors, the
most commonly seen is hemangiosarcoma, which accounts for approximately 46% of diagnosed
cardiac neoplasia, followed by aortic body tumors which account for 5% [2] [3]. Only 2% of
cardiac tumors are diagnosed as lymphoma [2]. Given the rarity of this disease, relatively few
cases have been studied and data regarding effective treatment or prognosis is limited.
Cardiac lymphoma is defined as lymphoma involving the heart or pericardium. It is
generally seen in middle aged (5-9 year-old), large breed dogs with a mean body weight of 40.5
kg [4]. Presenting history is generally acute with a median of three days of clinical signs. These
signs most commonly include lethargy, abdominal distension, dyspnea, anorexia, vomiting,
cough, and polydipsia. Physical examination findings are generally related to pericardial
effusion (weak pulses, pulses paradoxus, muffled heart sounds), right-sided heart failure (ascites,
jugular pulses, jugular distension), and forward heart failure (weakness, collapse) [4].
Diagnostic tests that have previously shown to be of value in the identification of cardiac
lymphoma include echocardiography for the identification of cardiac masses and pericardial
fluid analysis. Echocardiography has a variable sensitivity for detecting cardiac masses, ranging
from 16.7% to 82% [5] [6]. In general, it has been suggested that the sensitivity for detecting
cardiac masses improves when pericardial effusion is present. Cytologic evaluation of
pericardial effusion typically has a low diagnostic yield for cardiac neoplasia, with a recent study
demonstrating that this was diagnostic in only 7.7% of cases [7]. However, cardiac lymphoma is
often diagnosed using this method, which may be due to the better exfoliation of this neoplasm
compared to other cardiac tumors [4]. Using immunohistochemical staining of formalin-fixed
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paraffin-embedded tissue, lymphomas in cardiac tissue have been shown to be of both B and T
cell origin. To the author’s knowledge, this report describes the first case of the use of flow
cytometric analysis on pericardial fluid to confirm a diagnosis of T cell cardiac lymphoma in a
dog.
Extra-cardiac lymphoma may not be detected in patients presenting with lymphoma of
the heart. A study and a case report of 13 dogs reported primary cardiac lymphoma with no
evidence of lymphoma outside the heart and pericardium [4] [8]. Other reports have indicated that
cardiac lymphoma can be seen concurrently with lymphoma in the lungs or liver, suggesting
metastatic or multicentric disease [9] [10]. Yet another case report found that infiltration of
lymphoma into the cardiac tissues can be found incidentally on necropsy of patients with
peripheral lymphoma despite having no evidence of cardiac disease prior to death [6]. In the
patient described in this report, no evidence of extra-cardiac lymphoma was seen on thoracic
radiographs or physical examination, but an abdominal ultrasound or bone marrow aspirate were
not performed to evaluate for the presence of lymphoma in these tissues and further evaluation of
the hepatomegaly noted on abdominal radiographs was not performed. It is possible that the
hepatomegaly was due to lymphoma versus congestion secondary to right-sided heart failure.
The prognosis for cardiac lymphoma is unknown given the rarity of the condition and the
lack of literature available on survival with this disease. However, based on the largest study of
cardiac lymphoma available, the overall median survival time after diagnosis was 41 days in 12
dogs [4]. Patients in the latter study were either treated with combination chemotherapy protocols
such as cyclophosphamide, doxorubicin, vincristine, L-asparaginase, and prednisone or did not
receive any definitive treatment. Patients that only received palliative treatment, including
pericardiocentesis, pericardiectomy, or prednisone, had a mean survival time of 15 days, while
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those that received chemotherapy survived a significantly longer time of 157 days [4]. Based on
this report, it appears that treatment recommendations for cardiac lymphoma involve protocols
similar to those used for extra-cardiac lymphoma. However, regardless of the treatment plan
used, the prognosis for cardiac lymphoma is poor, with most patients succumbing to their cardiac
disease within several months.
CONCLUSION
This report describes a case of a rare neoplasm, canine cardiac lymphoma, and the
diagnostic tools used to identify it. Historically, cardiac lymphoma has often been a postmortem diagnosis on necropsy due to frequent lack of identifiable cardiac masses on
echocardiogram and lack of pericardial fluid analysis, presumably based on the assumed low
diagnostic yield of this method. This report emphasizes the value of cytological analysis of fluid
samples as a source of diagnostic information and introduces the use of flow cytometry as a tool
for confirming suspected cases of cardiac lymphoma.
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