Abstract
Primary Undifferentiated pleomorphic sarcomas (UPS) of the heart
extremely rare but aggressive tumors in the pediatric age group with an
extremely poor prognosis and no clear guidelines available for best
management. Diagnosis is often delayed, as they may be insidious and
masquerade as other cardiac benign tumors. We present a rare case of
cardiac UPS in a 13 year old with 40 months disease free survival
following a combination of early gross total surgical resection followed
by adjuvant chemotherapy and radiation therapy. The case highlights the
importance of a timely diagnosis and multimodal multidisciplinary
aggressive approach for improved survival.
Introduction
Primary malignant tumors of the heart in children and adolescents are
exceedingly rare. Undifferentiated pleomorphic sarcomas (UPS) are
cardiac sarcomas with no diagnostic histologic pattern or specific
immunohistochemical profile. UPS generally arise in the left atrium,
with a controversial prevalence depending on criteria adopted for
diagnosis; in a broad definition, it represents the most common sarcoma
type of the heart, accounting for 50% of cardiac
sarcomas.1, 2 On the other hand, benign cardiac tumors
represent the majority of cardiac masses in children with myxomas being
the most common.3
Cardiac sarcomas often present in an insidious manner in young adults
and are characterized by a dismal prognosis.4,5 It is
difficult to provide insight into the biologic behavior, treatment, and
prognosis of cardiac sarcomas in children because what is currently
known is based on individual adult case documentations. Treatment is
often based on experiences from similarly labeled malignant tumors
originating in other parts of the body. We are presenting a case of
primary cardiac UPS with 40 months disease free survival following
multimodal therapy provided by a multidisciplinary team.
Case
A 13-year-old female with no prior medical history presented to the
emergency department with a two-month history of pallor, cough, fatigue,
stomach pain and loss of appetite. Chest x-ray showed cardiomegaly at an
outside cardiology office and she was referred to us. She denied chest
pain, shortness of breath or palpitations. Patient endorsed a 5-pound
weight loss over 2 months. There was no history of contact with
tuberculosis, travel except Mexico and no exposure to pets. On
examination, the patient was afebrile, breathing comfortably with a
normal oxygen saturation. She was tachycardic and normotensive with no
postural deficit. She, had a 3/6 diastolic murmur, hepatomegaly 3 cm
below the costal margin, and jugular venous distension. There were no
rubs or thrills and her lungs were clear to auscultation.
Laboratory results were significant for leukocytosis, anemia,
hypophosphatemia, slightly elevated transaminases and dramatically
elevated inflammatory markers. An ECG revealed sinus tachycardia with
normal p-wave axis (+60°) and a low voltage QRS. Transthoracic
echocardiogram, CT and cardiac MRI (Fig 1A-E) confirmed a large
intracardiac mass that appeared to originate from the right sided atrial
septum, occupied most of the dilated right atrium and protruded through
the tricuspid valve into the RV outflow tract causing right tricuspid
valve obstruction. There was a moderate pericardial effusion. Right
ventricular ejection fraction (EF) and stroke volume and left ventricle
EF were moderately reduced. Considering the location, size and nature of
the mass, these findings were initially thought to be compatible with a
large right atrial myxoma. A full-body CT scan revealed no evidence of
distant metastasis.
After multidisciplinary discussions the patient underwent cardiac
surgery with a cardiopulmonary bypass that included a gross total
resection of the intracardiac mass, pericardial patch of the atrial
septum and suture annuloplasty of the tricuspid valve. Tricuspid valve
replacement was avoided due to risk of valve degeneration and
calcification in the setting if anticipated adjuvant chemo radiotherapy.
Histological analysis identified the tumor as an undifferentiated high
grade (FNCLCC grade 3) pleomorphic sarcoma and FISH analysis revealed a
MDM2 amplification (fig F -I). Post-operative course was uneventful and
post-operative MRI and PET scans showed no residual disease. Patient
developed moderate tricuspid regurgitation post operatively that
improved with time. Combined modality adjuvant therapy with chemotherapy
and radiation therapy (RT) followed recovery from surgery. She received
6 cycles of chemotherapy (21 day cycles of doxorubicin on Days 1, 2 (75
mg/m2/cycle) and Ifosfamide on Days 1, 2, 3 (9 g/m2/cycle) with G-CSF
support). She was referred for concurrent RT after 1 cycle of
chemotherapy. The 4D motion of the heart obtained from CT simulation was
used to define the target volumes. The decision was made to initially
include the entire heart to 25.2Gy) given the presence of a moderate
amount of pericardial effusion at diagnosis, infiltrative nature of
these tumors, inability to obtain negative resection margins in this
location, possible inaccuracy of MRI scans for delineating actual
cardiac tumor extent, intraoperative tumor spillage and targeting
uncertainties due to the current inability to deliver cardiac gated
IMRT. The RT planning target volumes and dose-volume histograms are
shown in Fig 2. She received a cumulative dose of 54 Gy in 30 fractions
from week 4 -10 of concomitant chemotherapy.
Her interval history was complicated by the development of
post-radiation pericardial effusion that was observed on her
surveillance echocardiograms starting 6 weeks post -radiation. She was
started on systemic corticosteroids with concurrent increase in her
Lasix dose and the effusion resolved within 10 weeks. The patient was
monitored with three monthly MRI, CT chest and transthoracic
echocardiograms for 24 months and then with six monthly MRI planned
until 60 months post-surgery. She is now 40 months post therapy and
continues to be in complete clinical and radiologic remission with
normal cardiac function and no late effects.