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: Janice.Tijssen@lhsc.on.ca

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

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Daniel LB, Mezody M, David TE.

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Virmani R, Hutchins GM. Primary

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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

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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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