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Febrile Illness in an Infant With an Intracardiac Inflammatory Myofibroblastic TumorRenée Pang, MD,a,b Neil H. Merritt, MD,a,b Michael J. Shkrum, MD,b,c Janice A. Tijssen, MDa,b
aDepartment of Pediatrics, Children’s Hospital, London
Health Sciences Centre, London, Ontario, Canada; and cUniversity Hospital, London Health Sciences Centre,
London, Ontario, Canada; and bUniversity of Western
Ontario, London, Ontario, Canada
Dr Pang conceptualized this report, interpreted
data, reviewed the references, drafted the initial
report, and critically reviewed the manuscript;
Dr Tijssen conceptualized the article, interpreted
the data, and critically reviewed the manuscript;
Dr Shkrum analyzed the pathology of the tumor,
interpreted data, provided images and information
the diagnosis of the tumor, and critically reviewed
the manuscript; Dr Merritt critically reviewed the
manuscript; and all authors approved the fi nal
manuscript as submitted.
DOI: 10.1542/peds.2014-3544
Accepted for publication Oct 14, 2015
Address correspondence to Janice A. Tijssen, MD,
Children’s Hospital, London Health Sciences Centre,
800 Commissioners Rd East, London, Ontario,
N6A5W9 Canada. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
Copyright © 2016 by the American Academy of
Pediatrics
FINANCIAL DISCLOSURE: The authors have
indicated they have no fi nancial relationships
relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors
have indicated they have no potential confl icts of
interest to disclose.
Inflammatory myofibroblastic tumors
(IMT) are rare types of spindle-
cell tumors that are characterized
by myofibroblastic lesions with
lymphoplasmacytic infiltrates.
IMTs are rare among the cardiac
tumors. Including our case, 49 cases
of intracardiac IMTs have been
reported across all age groups (see
Supplemental Information).1 Of these,
33 have been reported in the pediatric
population, with approximately
half of this group involving children
<12 months of age.2 Although IMTs
are generally described as benign
tumors, a small number demonstrate
neoplastic properties, such as local
recurrence after resection.3,4
The clinical presentation of IMTs often
includes fever, respiratory distress,
anemia, weight loss, and elevated
inflammatory markers. Patients may
also first present with cardiac signs
and symptoms such as respiratory
distress or sudden death. Deaths
due to the tumor are related to its
location in the heart; lesions located
near the coronary arteries, cardiac
valves, and ventricular outflow tracts,
in particular, are associated with
fatality.2,5
CLINICAL RECORD
An 11-month-old previously healthy
female presented to the emergency
department with a 5-day history of
intermittent fever and irritability.
There was no history of diarrhea,
bloody stools, or sick contacts. Her
medical history was otherwise
unremarkable. Growth parameters
were appropriate for age. Family
history was positive for sickle-cell
trait and negative for congenital heart
disease. She was brought to a walk-in
clinic on 2 occasions and discharged
from the hospital with a provisional
diagnosis of viral illness. Her
symptoms continued to worsen over
abstractWe report a case of a child with a right ventricular inflammatory
myofibroblastic tumor (IMT) who presented with fever, viral symptoms, and
abdominal discomfort. Including this case, 49 intracardiac tumors have been
previously reported in all age groups. The majority of intracardiac IMTs
occur in pediatric patients, with approximately half presenting in children
aged <12 months. Intracardiac IMTs are generally described as benign
tumors; however, depending on their location, the initial presentation may
involve heart failure or sudden death.1 In addition to cardiac signs and
symptoms, the clinical presentation of IMTs may also include constitutional
signs such as fever, anemia, and elevated inflammatory markers. This
case report reviews the diagnosis and management of IMTs, as well as the
histopathologic features of this rare tumor type. Clinicians should be aware
of their clinical presentation because early diagnosis and treatment can
significantly reduce morbidity and mortality.
CASE REPORTPEDIATRICS Volume 137 , number 2 , February 2016 :e 20143544
To cite: Pang R, Merritt NH, Shkrum MJ, et al.
Febrile Illness in an Infant With an Intracardiac
Infl ammatory Myofi broblastic Tumor. Pediatrics.
2016;137(2):e20143544
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PANG et al
the next 24 hours as she developed
decreased energy, a mild cough, and a
single episode of nonbilious emesis.
Presenting vital signs were significant
for mild tachycardia and tachypnea,
and her axillary temperature was
101.7°F. Examination revealed a
clinically stable child who was fairly
settled. She had a grade 3 systolic
crescendo-decrescendo murmur at
the left lower sternal border. She
had some substernal retractions,
but her lung fields were clear on
auscultation. Her abdomen was
significantly distended and tender
on examination. Liver edge was 2 cm
below the right costal margin. The
remainder of her examination was
normal. Laboratory investigations
revealed a white blood cell count
22 000 cells/μL, with a predominance
of neutrophils (13 400 cells/μL),
hemoglobin 8.1 g/dL, and platelets
469c000 cells/μL. C-reactive protein
was elevated at 12.3 mg/dL. She had
a compensated lactic acidosis. Chest
film revealed a cardiothoracic ratio
of 0.55, the upper limit of normal, but
lung fields were clear. An abdominal
ultrasound revealed mild hepatic
enlargement, free fluid, and a small
right pleural effusion. The patient
was admitted to pediatric general
surgery for further investigation
and management of a presumed
gastrointestinal process and treated
empirically with antibiotics. Given
the new murmur, cardiology was
consulted. The patient remained
stable overnight.
On postadmission day 1, her
tachypnea progressed from a
respiratory rate of 30 to 50 breaths
per minute on room air while
maintaining oxygen saturation
of 100%. Her respiratory status
continued to deteriorate over
the course of a few hours as she
developed progression of her cough,
grunting, and perioral cyanosis.
She was transferred to the ICU for
respiratory support and monitoring,
and cardiology was reconsulted
on an urgent basis. She required
active resuscitation and inotropic
support to maintain perfusion.
An echocardiogram performed
during the resuscitation revealed a
right ventricular mass obstructing
her right ventricular outflow
tract, significant right ventricular
hypertrophy, and depressed left
ventricular filling (Fig 1). The
patient developed a narrow complex
bradycardia and eventual cardiac
arrest. The patient died during
resuscitation attempts.
At autopsy, cardiac evaluation
revealed a heart that weighed 65.5 g
(normal range 49 ± 6 g).6 The right
ventricle width measured 0.4 cm
and was severely dilated. There was
a visible bulge on the anterior basal
area of the heart corresponding
to a yellow-red polypoid tumor,
measuring 2.7 × 2.2 × 1.5 cm, arising
from the posterior wall of the right
ventricle just below the pulmonary
valve (Fig 2A). Both atria were
dilated. No other abnormalities were
noted in the cardiac structure. On
examination of the body cavities,
bilateral pleural effusions (right 30
mL, left 100 mL), hydropericardium
(30 mL), and ascites (300 mL)
were noted. Postmortem blood,
cerebrospinal fluid, and pleural
fluid cultures were negative. A
postmortem nasopharyngeal swab
for respiratory viruses was also
negative.
Histologic examination revealed a
spindle-cell lesion with scattered
mitoses of up to 2 mitoses per 10
high power field (Fig 2B). There
was no invasion of the myocardium.
There were occasional foci of
mononuclear inflammatory cells, and
multiple areas of focal necrosis with
overlying thrombi. The tumor stained
positive for vimentin, supporting a
mesenchymal origin. The spindle-
cell component of the lesion stained
positive for muscle-specific actin
and smooth muscle actin, consistent
with a myofibroma (Fig 2C). Desmin
(various muscle types) and myogenin
(skeletal muscle) both stained
negative. The tumor also stained
negative for anaplastic lymphoma-
kinase-1 (ALK-1). The tumor stained
negative for other cell lineages,
including S100 and cytokeratin AE1/
AE3 (CAE1/AE3), therefore negative
for neurogenic and epithelial
markers, respectively. The final
diagnosis of IMT was made on the
basis of the presence of inflammatory
cells with positive staining for
muscle-specific actin and smooth
muscle actin.
DISCUSSION
Cardiac tumors are rare in the
pediatric population. The incidence
in both adults and children is
between 0.0017% and 0.028%.7
Rhabdomyomas are the most
common cardiac tumor in children
>12 months of age, encompassing
>60% of all childhood cardiac
tumors, followed by fibromas
2
FIGURE 1Echocardiogram of tumor. A, Parasternal long axis view of intracardiac infl ammatory myofi broblastic tumor. B, Apical 4-chamber view with severe dilation of right ventricle (RV). LV, left ventricle; RA, right atrium.
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PEDIATRICS Volume 137 , number 2 , February 2016
and myxomas.7,8 Although
intracardiac IMTs are rare, they
have a predilection for younger
patients. Including this case, only 49
intracardiac IMTs have been reported
worldwide; of these, >approximately
two-thirds have appeared in patients
under age 18 years (33 of 42), with
about half of them appearing under
age 12 months (17 of 33).1,3–5,8
The differential diagnosis for
intracardiac IMTs include some of
the more common cardiac tumors,
particularly rhabdomyomas,
myxomas, and fibromas. These are
differentiated from IMTs based on
histology and extent of invasion into
the myocardium.9,10 IMTs appear
histologically similar to myosarcomas
but can be differentiated on the
basis of their having less cellular
pleomorphism, atypia, and fewer
mitotic figures1,10 and not invading
into the myocardium. ALK-1 is
positive in 35% of IMTs,11 although
a negative result does not rule
out the diagnosis because several
intracardiac IMTs have previously
stained negative.2,8,12,13 IMTs
are described as benign reactive
lesions; although the exact etiology
of the tumor is unknown, several
studies have associated IMTs with
Epstein-Barr infection.8,11–13 Listeria monocytogenes has also been
reported to cause IMTs as well.14
Local recurrence is reported in up to
∼10% of cases.4 Recent research has
also suggested that IMTs may exhibit
some chromosomal aberrations at
the 2p23 locus, further supporting
the possibility of a neoplastic
mechanism of disease.11
Intracardiac IMTs have a variable
clinical presentation depending on
the site of the tumor. They are also
usually associated with constitutional
signs and symptoms including fever,
anemia, polyarthritis, and vascular
compromise, which are thought to be
caused by the release of cytokines by
IMTs, interleukin-6, in particular.5,11
They can also present with dyspnea,
which may manifest as respiratory
distress in infants that should be
monitored and investigated.
Young infants and children in heart
failure may appear otherwise well
during the earlier stages because
their cardiovascular physiology
compensates significantly to
maintain cardiac output. However,
decompensation is rapid if the
underlying cause is not addressed.
The location of the tumor for
our patient was challenging for
stabilization because the mass
was obstructing the right outflow
tract, limiting blood delivery to the
pulmonary and systemic circulation
systems. Rates of sudden death
due to cardiac tumors is ∼0.06%
in persons 34 years and younger.15
Poor prognosis is associated with
lesions involving the coronaries,
cardiac valves, or ventricular outflow
tracts.2,5
Although serum laboratory
investigations may offer some
information, diagnostic imaging is
the mainstay for diagnosis of cardiac
tumors. An echocardiogram is the
most useful modality to confirm
diagnosis of an intracardiac mass.16
The differential diagnosis for an
intracardiac mass is included in Table
1. Although echocardiography can be
helpful to differentiate the etiology of
the lesion,16 histologic examination
remains the gold standard for
confirmation of the diagnosis.
IMTs are considered a benign
tumor. Intracardiac IMTs are treated
definitively by completely resecting
the tumor. The prognosis after
excision is good, although there is
3
FIGURE 2Gross pathology and histology of the infl ammatory myofi broblastic tumor. A, Gross pathology of the tumor. B, Hematoxylin and eosin stain. Magnifi cation 200×. C, Immunoperoxidase stain. Magnifi cation 200×. Smooth muscle actin stain positive.
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PANG et al
a 10% chance of local recurrence.4
For unresectable tumors, heart
transplantation may be considered
as an option, although there has been
only 1 successful case reported for
this indication.17 Corticosteroids
have been used previously as adjunct
therapy for difficult resections and
for IMTs in other body sites. There
is no current evidence that they
prolong survival for intracardiac
tumors in particular.12 Therefore,
surgical resection remains the
mainstay of treatment.
CONCLUSIONS
Inflammatory myofibroblastic tumors
may present with constitutional
symptoms that can mimic other
common illnesses. Congestive heart
failure and obstructive shock are
end-stage clinical presentations that
require urgent echocardiography
and imaging for diagnosis
and management. Laboratory
investigations can provide ancillary
information about perfusion
and oxygenation. A high index of
suspicion is necessary to make the
diagnosis of this rare lesion because
timely surgical resection is ultimately
required for the definitive and
potentially lifesaving management.
ACKNOWLEDGMENTS
The authors thank Dr Eva Welisch for
providing the clinical interpretation
of the images and Travis Kowlessar,
who performed the echocardiogram
and provided the images for this
publication.
ABBREVIATION
IMT: inflammatory
myofibroblastic tumor
REFERENCES
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4
TABLE 1 Differential Diagnosis of Intracardiac Mass
Cause Examples Ultrasound Features
Thrombus Hypercoagulability Coexistence of underlying abnormalities of
regional or global ventricular wall motion
Stasis
Previous endothelial injury
Primary tumors Myxoma No calcifi cations in myxoma
Rhabdomyosarcoma Solitary mass
Myxosarcoma Stalk attachment
Fibrosarcoma May involve invasion of myocardium if malignant
Myofi broma
Metastatic tumors Small cell carcinoma Extensive involvement
Leiomyosarcoma Cardiac dysfunction
Lymphoma Infi ltration of coronary arteries
Thyroid cancer Multiple tumors present
Melanoma
Bronchial sarcoma
Lymphoma
Rhabdomyosarcoma
Renal cell carcinoma
Infectious
vegetation
Staphylococcus aureus Mobile and irregular masses attached to
cardiac valves
Viridans α-hemolytic
Streptococcus
Evidence of valvular destruction
HACEK organisms
Viral
Fungal
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PEDIATRICS Volume 137 , number 2 , February 2016
13. Butany J, Dixit V, Leong SW,
Daniel LB, Mezody M, David TE.
Infl ammatory myofi broblastic tumor
with valvular involvement: a
case report and review of the
literature. Cardiovasc Pathol.
2007;16(6):359–364
14. Adler A, Fimbres A, Marcinak J,
et al. Infl ammatory pseudotumor
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monocytogenes infection. J Infect.
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15. Cina SJ, Smialek JE, Burke AP,
Virmani R, Hutchins GM. Primary
cardiac tumors causing sudden
death: a review of the literature.
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masses detected by echocardiography:
case presentations and review
of the literature. Clin Cardiol.
2000;23(9):702–708
17. Di Maria MV, Campbell DN, Mitchell
MB, Lovell MA, Pietra BA, Miyamoto SD.
Successful orthotopic heart transplant
in an infant with an infl ammatory
myofi broblastic tumor of the left
ventricle. J Heart Lung Transplant.
2008;27(7):792–796
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DOI: 10.1542/peds.2014-3544 originally published online January 21, 2016; 2016;137;Pediatrics
Renée Pang, Neil H. Merritt, Michael J. Shkrum and Janice A. TijssenTumor
Febrile Illness in an Infant With an Intracardiac Inflammatory Myofibroblastic
ServicesUpdated Information &
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DOI: 10.1542/peds.2014-3544 originally published online January 21, 2016; 2016;137;Pediatrics
Renée Pang, Neil H. Merritt, Michael J. Shkrum and Janice A. TijssenTumor
Febrile Illness in an Infant With an Intracardiac Inflammatory Myofibroblastic
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