Pediatric Malignant Pericardial Effusion

Pericardial involvement in patients with malignancy is common. ^{[1, 2]} Widespread use of noninvasive diagnostic techniques, such as echocardiography and computed tomography (CT) scanning, has increased awareness of this diagnosis. The mere presence of pericardial effusion does not necessarily imply pericardial infiltration by malignant cells.

Pericardial malignancy is often asymptomatic. It is observed on chest radiography performed to evaluate the lungs or diagnosed as an incidental finding at autopsy. It can also present in antenatal scans, especially with fetal teratoma. Although pericardial malignancy may be reported as an incidental finding, it may have contributed to the symptoms and even to death.

Medical care is dictated mainly by the general condition of the patient and the underlying malignancy. The safety and effectiveness of surgical drainage of pericardial fluid via pericardiectomy (complete or partial) or the creation of a pericardial window are well recognized. Further inpatient care is determined by the underlying condition. Further outpatient care is often required to look for evidence of constrictive pericarditis. 

The pericardium consists of 2 layers, the visceral pericardium (epicardium) and the parietal pericardium, which enclose a potential space (ie, the pericardial cavity) between them. This cavity is normally lubricated by a very small amount of serous fluid (< 30 mL in adults). Inflammation of the pericardium or obstruction of lymphatic drainage from the pericardium of any etiology causes an increase in fluid volume, referred to as a pericardial effusion.

Malignant involvement of the pericardium may be primary (less common) or secondary (spreading from a nearby or distant focus of malignancy). Secondary neoplasms can involve the pericardium by contiguous extension from a mediastinal mass, nodular tumor deposits from hematogenous or lymphatic spread, and diffuse pericardial thickening from tumor infiltration (with or without effusion). In diffuse pericardial thickening, the heart may be encased by an effusive-constrictive pericarditis.

Other rare mechanisms include chronic myelomonocytic leukemia and intrapericardial extramedullary hematopoiesis with preleukemic conditions or during blast crisis in chronic myeloid leukemia. Obstruction of lymphatic drainage by mediastinal tumors, either benign or malignant, can also give rise to pericardial effusion, which can be chylous. These mechanisms may act independently or jointly in any particular child with malignancy. The underlying myocardium is not involved in most patients.

Pathogenesis of clinical manifestations

In healthy individuals, the pericardium does not limit filling of the cardiac chambers either at rest or during exercise. When pericardial effusion occurs, chamber capacity may be reduced. Venous return may be severely limited, and thus, cardiac output may also be severely limited. The capacity of the pericardial space is influenced by its natural stiffness. Rapid accumulation of fluid is poorly tolerated, whereas slow accumulation may allow large amounts of pericardial fluid to collect without producing symptoms.

When pressure is increased within the pericardial space, filling pressure is elevated in all chambers of the heart. In advanced stages, right and left atrial mean pressures and right and left ventricular end-diastolic pressures are virtually identical to the intrapericardial pressure. Therefore, the clinical features result from the limitation of cardiac output and elevated venous pressures.

Pulsus paradoxus

In healthy individuals, inspiration causes the systolic blood pressure to fall slightly as a result of the greater volume of blood accommodated by the pulmonary vascular bed. This occurs despite inspiratory increase in venous return to the right heart. In cardiac tamponade, right ventricular filling is maintained at the expense of restricted left ventricular filling, and the systolic blood pressure falls further (>10 mm Hg).

This exaggerated fall in systolic blood pressure with inspiration is referred to as pulsus paradoxus. It is an important sign of cardiac tamponade, though on occasion, severe respiratory distress of any cause (asthma, emphysema, pleural effusion) may give rise to this sign.

Primary malignant neoplasms that may give rise to pericardial effusion include the following:

• Pericardial mesothelioma

• Fibrosarcoma

• Angiosarcoma

• Liposarcoma

• Lymphoma

• Malignant pericardial teratoma

• Rhabdomyosarcoma with tuberous sclerosis

• Pheochromocytoma

• Kaposi sarcoma and primary cardiac lymphoma in association with human immunodeficiency virus (HIV) infection

• Primary effusion lymphoma (PEL) associated with human herpesvirus 8 (HHV8) ^[3]

• Intrapericardial teratoma in the fetus and neonate

Metastatic or infiltrative diseases that may give rise to pericardial effusion include the following:

• Non-Hodgkin lymphoma

• Neuroblastoma

• Ganglioneuroblastoma

• Pheochromocytoma

• Sarcomas

• Wilms tumor

• Hodgkin lymphoma

• Primary mediastinal (thymic) B-cell lymphoma

• Adenocarcinoma

• Mesothelioma

• Pulmonary lymphangiomatosis

• Malignant fibrous histiocytomas

• Leiomyosarcomas

• Liposarcomas

• High-grade sarcomas

• Burkitt lymphoma

Pericardial effusion is a common cause of pericarditis, occurring in approximately 5-15% of US patients with malignant neoplasms, according to autopsy data. Most cardiac tumors in infants and children are benign (eg, rhabdomyoma and fibroma) and are unlikely to be associated with pericardial involvement. ^[4] A study of 236 children in Poland reported cardiac involvement in 15% of children, including pericardial effusion in 7% of children. ^[5] A review from the United States ranked pericardial effusion as an important oncologic emergency. ^[6]

Age- and sex-related demographics

Children of all ages are affected, but pericardial effusion is more common in older children and adolescents. In a study by Medary et al, the mean age was 14 years. ^[7] This finding may be related to the longer survival of older children with malignancy. Both sexes are affected. Medary et al reported a higher incidence in males than in females, with a ratio of 7:3. ^[7]

Children with pericardial involvement due to malignancy have more extensive disease and hence a worse prognosis; pericardial tamponade may add to the mortality unless promptly detected and appropriately treated. ^{[5, 8]} Educate patients about cardiac symptoms of tamponade and the need to follow up with regular examination.

Detection of malignant cells in pleural, peritoneal, and pericardial fluids of patients with cancer marks the presence of metastatic disease, usually establishing a grave prognosis; however, all patients with malignancy and pericardial effusion do not have metastatic involvement.

Immediate relief of large effusions is essential to prolong survival.