Pericardial Tumour

Pericardial tumours are neoplasms arising in or involving the pericardium. Secondary involvement by metastasis or direct invasion is 20 to 40 times more common than primary tumours. Primary tumours are rare, and about half of primary malignant pericardial tumours are mesotheliomas.

Primary benign tumours are lipoma, teratoma, haemangioma, lymphangioma, fibroma and paraganglioma. Primary malignant tumours are mesothelioma, angiosarcoma and other sarcomas (synovial, liposarcoma, fibrosarcoma), solitary fibrous tumour, lymphoma and germ cell tumours. Pericardial cysts are not neoplasms.

Secondary tumours are from lung (about 40%), breast (about 20%), lymphoma, leukaemia, melanoma, oesophagus and ovary. Pericardial mesothelioma has a weak link with asbestos exposure, unlike pleural disease. Onset is usually in the fourth to seventh decades. Teratoma occurs in infants and foetuses.

Prognosis of primary malignant pericardial tumours is poor, with median survival of about 6 months for mesothelioma. Benign tumours are curable by excision.

Pathophysiology.

Tumour thickens and encases the pericardium, producing bloody exudative effusion, tamponade and constrictive physiology. It may invade the myocardium, great vessels and coronary arteries.

Arrhythmia follows myocardial invasion, and obstruction of the superior vena cava, pulmonary veins or outflow tracts occurs with mediastinal masses.

Mesothelioma shows loss of BAP1 and CDKN2A in many cases. Large teratomas compress the heart and cause foetal hydrops.

Dyspnoea, orthopnoea, chest pain, cough, palpitations, fatigue, weight loss and abdominal swelling. Findings of tamponade (hypotension, raised jugular venous pressure, pulsus paradoxus), constriction (Kussmaul sign, ascites, oedema), arrhythmia, superior vena cava obstruction and heart failure. Some tumours are found incidentally on imaging. Foetal and neonatal teratoma presents with hydrops, polyhydramnios and respiratory distress.

• Echocardiography: effusion, pericardial mass, thickening, tumour extension into the heart, and tamponade or constriction.
• CT chest, abdomen and pelvis with contrast: nodular enhancing pericardial thickening, calcification, mass and extent. Cardiac MRI characterises tissue: lipoma is bright on T1 and suppresses with fat saturation, teratoma is multilocular and cystic with calcification, haemangioma is bright on T2 with enhancement, and malignant tumours enhance heterogeneously with invasion.
• PET-CT to stage and find a primary or biopsy target.
• Cytology of pericardial fluid is positive in less than a third of primary mesotheliomas, so tissue is needed: pericardioscopic, thoracoscopic or surgical biopsy. Immunohistochemistry for mesothelioma: positive calretinin, WT1, CK5/6 and D2-40, negative TTF-1, Ber-EP4 and CEA, with BAP1 loss supporting malignancy. Solitary fibrous tumour is CD34 and STAT6 positive.
• Tumour markers (alpha fetoprotein, beta-hCG in germ cell tumours), LDH, NT-proBNP, troponin, full blood count, creatinine and liver tests.

Differential diagnosis.

• Metastatic carcinoma, lymphoma and thymic tumours.
• Tuberculous, radiation and idiopathic constrictive pericarditis.
• Pericardial cyst, haematoma and loculated effusion.
• Cardiac sarcoma and myxoma.

Manage by a multidisciplinary team (cardiology, cardiothoracic surgery, oncology, radiology, pathology).

Emergencies. Tamponade: urgent drainage (pericardiocentesis with a pigtail catheter for 3 to 7 days, or a surgical window), with oxygen, crystalloid 250 to 500 mL and noradrenaline 0.05 to 0.5 microgram/kg/min while drainage is arranged. Avoid diuretics, vasodilators and positive pressure ventilation where possible.

Benign tumours. Complete surgical excision is curative for symptomatic or growing tumours. Small asymptomatic lipomas and fibromas are followed with MRI every 6 to 12 months. Foetal and neonatal teratoma: urgent excision after delivery, with foetal pericardiocentesis for hydrops in selected centres.

Pericardial mesothelioma and other primary malignancy.

• Surgery: pericardiectomy or debulking relieves constriction or recurrent tamponade, and complete resection is possible only in a few patients.
• Pemetrexed 500 mg/m2 intravenously on day 1 with cisplatin 75 mg/m2 on day 1, every 21 days for up to 6 cycles.
• Folic acid 350 to 1000 microgram orally daily starting 7 days before the first dose and continuing until 21 days after the last.
• Vitamin B12 1000 microgram intramuscularly 1 week before the first dose and then every 9 weeks.
• Dexamethasone 4 mg orally twice daily on the day before, the day of and the day after each dose.
• Antiemetics with a 5-HT3 antagonist, an NK1 antagonist and dexamethasone, and hydration.
• Avoid pemetrexed when creatinine clearance is under 45 mL/min and avoid NSAIDs for 2 days before, on the day of and for 2 days after each dose when clearance is 45 to 79 mL/min.
• Check creatinine, magnesium and blood count before each cycle, and audiometry with cisplatin.
• Carboplatin (AUC 5) replaces cisplatin when it is not tolerated.
• Nivolumab 360 mg intravenously every 3 weeks with ipilimumab 1 mg/kg every 6 weeks for up to 2 years is used in pleural mesothelioma, and pericardial use is by extrapolation; monitor for myocarditis, troponin and thyroid, liver and adrenal toxicity.
• Sarcoma: surgery when resectable, with doxorubicin 75 mg/m2 intravenously every 3 weeks (lifetime ceiling 450 to 550 mg/m2; echocardiography before each cycle) or ifosfamide based regimens. Lymphoma: regimens by histology.
• Palliative radiotherapy for symptomatic masses, with attention to cardiac dose.

Effusion. Extended catheter drainage, then pericardial window for recurrence. Intrapericardial sclerosis or cisplatin is used in selected malignant effusions by specialist direction.

Arrhythmia and heart failure. Anticoagulate atrial fibrillation (apixaban 5 mg twice daily, 2.5 mg twice daily if two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over), avoiding it when bleeding or biopsy is planned. Treat constriction with diuretics (furosemide 40 to 80 mg orally daily) while awaiting surgery.

Monitoring. Echocardiography after drainage and every 1 to 3 months. Imaging for response every 2 to 3 cycles of chemotherapy. Full blood count, creatinine and magnesium before each cycle.

Referral and escalation. Refer every suspected pericardial tumour to a tertiary cardiac and oncology centre. Urgent referral for tamponade, constriction, arrhythmia, superior vena cava obstruction or foetal hydrops. Early palliative care.

Special groups.

• Pregnancy: avoid pemetrexed, cisplatin, ipilimumab and nivolumab; manage by delivery planning and multidisciplinary care.
• Children and infants: surgical excision for teratoma; chemotherapy dosing by a paediatric oncology team.
• Kidney impairment: avoid pemetrexed when creatinine clearance is under 45 mL/min and cisplatin when it is under 60 mL/min.
• Older adults: lower intensity regimens, and goals-of-care discussion early.