Pediatric Malignant Pericardial Effusion Workup

Updated: Jul 03, 2019
  • Author: Poothirikovil Venugopalan, MBBS, MD, FRCPCH; Chief Editor: Syamasundar Rao Patnana, MD  more...
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Workup

Laboratory Studies

The following blood investigations may be ordered, as dictated by the patient’s general condition:

  • Complete blood cell (CBC) count with platelet count and white blood cell (WBC) differential

  • Blood film (smear)

  • Serum chemistry

  • Erythrocyte sedimentation rate (ESR)

  • C-reactive protein (CRP) level

  • Blood cultures

Levels of the following markers of specific malignancy may help in assessing disease progression:

  • Serum alpha-fetoprotein (AFP)

  • Serum cancer antigen (CA)-125

The following markers of malignancy in pericardial fluid cells may be useful:

  • Human telomerase reverse transcriptase (hTERT) mRNA expression may be detected in abnormal cells in body fluids by using in situ hybridization (ISH)

  • Molecular genetic studies can also be helpful in the analysis of lymphocyte-rich serous pericardial effusion.

  • An immunocytochemical test panel has also been suggested in selected cases

  • Vascular endothelial growth factor levels are elevated in malignant pericardial effusion. [13]

Double immunohistochemical antibody studies for EZH2 nuclear staining and MOC-31 membranous staining on serosal effusions may help clinicians to differentiate between benign and malignant effusions. [1] In a retrospective study of 142 patients diagnosed with either benign (n = 53) or malignant (n = 89) cytology on the basis of clinical, radiologic, histopathologic, and follow-up data, no benign cases expressed EZH2 or MOC-31 markers, whereas 93% and 96% of the malignant cases, respectively, expressed these markers. [1]

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Electrocardiography

Changes on electrocardiography (ECG) are nonspecific and may represent the effect of pericardial inflammation on the underlying myocardium.

Low voltage QRS complexes (35%) are seen, especially with moderate to large effusions. ST-segment elevation is found. T-wave inversion is noted. Development of arrhythmias (eg, atrial tachycardia, atrial fibrillation, or heart block) is observed. Electrical alternans (seen in 17% of cases), a beat-to-beat variation in QRS amplitude, occurs with excessive motion of the heart within the fluid-filled pericardial space.

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Chest Radiography

Chest radiography reveals varying degrees of cardiomegaly, depending on the amount of pericardial fluid and its rate of accumulation (see the image below). Rapidly accumulating effusion is associated with relatively minimal cardiomegaly, whereas massive effusions produce a large cardiac shadow, causing the characteristic water-bottle heart or triangular heart with smoothed-out cardiac borders.

Plain chest radiograph from 3-month-old infant wit Plain chest radiograph from 3-month-old infant with pneumonia and malignant pericardial effusion, showing cardiomegaly and bilateral pneumonic patches.

Pleural effusion, mediastinal widening, hilar mass, or, less commonly, irregular nodular contour of the cardiac silhouette or a bony or parenchymal metastatic deposit may indicate underlying disease. Rarely, pericardial calcification may be evident.

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Echocardiography

Echocardiography is the primary study performed for diagnosis and quantification of the effusion, as well as for guidance of needle pericardiocentesis. Echocardiography has a 96% diagnostic accuracy in pericardial effusion.

Pericardial fluid gives the appearance of an echo-free space between the epicardial and pericardial reflections. This is evident in both 2-dimensional images (see the first image below) and M-mode images (see the second image below).

Two-dimensional echocardiograph from subcostal win Two-dimensional echocardiograph from subcostal window, showing large pericardial effusion.
M-mode echocardiograph from child with pericardial M-mode echocardiograph from child with pericardial effusion.

When effusion is minimal, it accumulates posterior to the left ventricle and is more apparent in systole. When effusion is massive, fluid is observed all around the heart and throughout the cardiac cycle. Diastolic ventricular filling is abnormal secondary to cardiac compression.

A swinging motion of the heart may be observed within the pericardial cavity, along with abnormalities of septal motion, dilation of the inferior vena cava, and loss of respiratory caval motion. Irregular undulating masses that protrude into the pericardial space, the atria, the ventricles, or even the pulmonary arteries are reported.

Hemodynamic impairment or cardiac tamponade is deemed to be present in the presence right atrial collapse (buckling of the right atrial wall into the right atrium) in late diastole and/or right ventricular free-wall collapse in early diastole. [14] Exaggeration of respiratory variation in transvalvar Doppler flow velocities is seen with tamponade. [15] ; decreased transmitral Doppler flow velocity greater than 30% during inspiration compared with expiration may be indicative of cardiac tamponade and may require pericardial decompression by a pericardial tap or other means as per the patient’s clinical status.

Fetal echocardiography can identify fetal pericardial effusion secondary to fetal pericardial malignancy (most commonly, teratoma).

Transesophageal echocardiography (TEE) provides information regarding the presence and location of space-occupying masses within the pericardium.

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CT, MRI, and Radionuclide Imaging

Computed tomography (CT) scanning reveals the thickness and density of the pericardium and content of the pericardial space. It aids in the identification of constrictive pericarditis by providing additional information on the status of the vena cava, atria, ventricles, and pleura. The minimum amount of pericardial fluid that can be detected by CT scanning is estimated to be 10 mL. CT scanning provides added information regarding the presence and location of space-occupying masses within the pericardium and the adjacent mediastinum and lungs.

Magnetic resonance imaging (MRI) provides added information regarding the presence and location of space-occupying masses within the pericardium and the adjacent mediastinum and lungs. [16] In addition, this technique is more sensitive than CT in differentiating malignant lesions from benign ones.

Radionuclide imaging can demonstrate a pericardial effusion in previously undiagnosed pericardial disease.

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Diagnostic Pericardial Drainage

Pericardial drainage is used to diagnose the cause of the malignant effusion, assess the cytology, and treat hemodynamic compromise in the presence of cardiac tamponade. In a study of 480 pericardiocentesis specimens, investigators determined that a minimum volume of more than 60 mL is required for cytologic evaluation to ensure an adequate diagnosis of pericardial fluids. [17] When compared with pericardial biopsy, cytology of pericardial fluid volumes below 60 mL had a 70.0% sensitivity and detected fewer malignancies.

Malignancy may be first suspected from pericardial fluid analysis in as many as 5% of these patients. A catheter drainage technique is commonly used. Ultrasonographic guidance adds to the safety of the procedure, [18] but it is not a requisite with emergency drainage.

For pericardiocentesis, insert a beveled, sharp needle beneath the xiphoid process, and angle upward and leftward toward the left shoulder. Sometimes, a pop is felt as the needle is passed into the pericardium. Attempt to withdraw fluid with each advance of the needle. If fluid is obtained, remove enough to alleviate tamponade. Even a small amount often provides significant benefit.

Process the pericardial fluid for cytology, biochemistry, and culture and sensitivity, including viral and fungal cultures in relevant cases. Exudates differ from transudates in that they demonstrate higher leukocyte counts, lower glucose levels, higher protein contents, and higher specific gravity. Cytospin preparations can be stained with Wright-Giemsa stain to identify cellular morphology that, in turn, can be used to test for immunologic markers and for electron microscopy.

Potential complications of the procedure include myocardial puncture, coronary artery or vein laceration, hemopericardium, laceration of the internal mammary artery, pneumothorax, and liver and aortic injury.

In the presence of significant effusion, maintain good hydration and effective filling pressures to help maintain perfusion until pericardiocentesis can be performed.

Continuous closed drainage of the pericardial space is accomplished by advancing a pigtail catheter over a guide wire. This is necessary for patients in whom the effusion reaccumulates rapidly.

Video-thoracoscopic pericardial drainage is a safe and effective for loculated pericardial effusions previously treated by percutaneous drainage maneuvers and patients with concomitant pleural disease. [19, 20] Percutaneous balloon pericardiotomy has also been tried for management of recurrent malignant pericardial effusion. [21, 22]

Fetal pericardiocentesis has been used in the treatment of pericardial effusion secondary to fetal teratoma. Pericardioamniotic shunting has been tried in fetal malignant pericardial effusion, with variable success. [9]

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Pericardial Biopsy

Specimens for pericardial biopsy can be obtained either by open pericardiotomy or during thoracotomy (the latter is relatively rare). Pericardial biopsy has a sensitivity of approximately 55% for diagnosing malignant involvement; however, when used in conjunction with cytologic analysis of the pericardial fluid, it has a sensitivity of nearly 100%.

Open pericardial biopsy may be required if initial cytologic analysis yields negative results. Obtaining a larger biopsy specimen by means of open biopsy should provide a histologic diagnosis in as many as 90% of cases. The procedure carries significant risk in patients who are critically ill, but a false-negative diagnosis may occur if the tissue sample is too small.

Biopsy specimens are subjected to histologic and immunohistologic examination, polymerase chain reaction (PCR) evaluation, or in situ hybridization (ISH) analysis for microbial DNA and ribonucleic acid. [23]

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Other Diagnostic Procedures

Pericardioscopy can reveal neoplastic effusions both by permitting direct observation and by obtaining a biopsy of the pericardium for further analysis.

Cardiac catheterization is not required for diagnosis of pericardial effusion. However, there are potential indications for its use, such as the following:

  • Suspected superior venacaval obstruction and pulmonary microvascular tumor (lymphangitic tumor) may occur with malignant cardiac tamponade and contribute to the development of facial edema and jugular venous distention

  • Cyanosis, hypoxemia, and elevated pulmonary vascular resistance may indicate pulmonary microvascular tumor (lymphangitic tumor); the diagnosis can be established by obtaining a blood sample for cytologic analysis from the pulmonary capillary wedge position using the right-heart catheter

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Histologic Findings

Malignant pericardial effusion is often hemorrhagic or serosanguineous, but these findings alone are not sufficient to differentiate neoplastic causes from radiation-related or idiopathic causes. Because treatment strategies differ, it is essential to carry out a meticulous cytologic examination of the pericardial fluid (see the images below) so as to help differentiate malignant pericarditis from other causes of pericardial effusion.

Cytologic features of malignant pericardial effusi Cytologic features of malignant pericardial effusion. Smear of centrifuged pericardial fluid from patient with malignant pericardial involvement from lymphoma. Low-power view showing numerous mononuclear cells along with large atypical malignant cells.
Cytologic features of malignant pericardial effusi Cytologic features of malignant pericardial effusion. Smear of centrifuged pericardial fluid from patient with malignant pericardial involvement from lymphoma. High-power view showing morphologic details of malignant cells. These cells are large and show oval hyperchromatic nuclei, some of them having nucleoli. Cytoplasm is reduced to thin rim.

False-negative results on cytology are uncommon in carcinomatous pericarditis, but when such a result does occur, it may be due to scant cellularity or the presence of obscuring blood. False-negative results are more common with lymphoma and mesothelioma. Chylothorax is most often reported with mediastinal lymphangioma.

Detection of malignant cells in effusions is facilitated by immunocytochemistry studies using a wide panel of antibodies. [24] BerEP4 and B72.3 appear to be the best markers when both sensitivity and specificity are considered, followed by BG8. Carcinoembryonic antigen (CEA) and CA-125 have a limited role in the detection of metastases from gynecologic tumors because the former has low sensitivity and the latter has low specificity.

Flow cytometry can also be used to detect DNA diploidy (reflecting a benign condition) and aneuploidy (reflecting a malignancy), but the results have not been uniformly convincing. The low sensitivity of flow-cytometric DNA analysis does not favor its routine use.

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