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.