Primary Pericardial Mesothelioma Unique Case and Literature Review

Abstract

A 72-year-old woman, on warfarin therapy and with a remote history of breast cancer and radiation treatment, presented with a 10-day history of nausea, dyspnea, dry cough, and dizziness. An electrocardiogram showed new-onset atrial fibrillation. Computed tomography of the chest revealed multiple pulmonary emboli and a pericardial effusion. Echocardiography showed a pericardial effusion with tamponade characteristics. The patient's condition deteriorated, and a pericardiectomy was performed. Histologic evaluation confirmed primary pericardial mesothelioma. She underwent palliative treatment and died 3 months after discharge from the hospital. We discuss the patient's case and the nature of primary pericardial mesothelioma, a rare oncologic entity.

Primary pericardial mesothelioma is an oncologic rarity, with a reported prevalence of <0.002%.¹ Unlike pleural and peritoneal mesotheliomas, which are usually associated with asbestos exposure, the cause of pericardial mesothelioma is less clear. Factors other than asbestos exposure that may play a role include genetic predisposition, immunologic impairment, infection, radiation, dietary factors, and recurrent serosal inflammation.² Clinical manifestations of the neoplasm include constrictive pericarditis, cardiac tamponade, and heart failure. Because of late presentation and few treatment approaches, primary pericardial mesothelioma carries a poor prognosis. We report a case of this rare tumor in a woman who had been exposed to therapeutic radiation for breast cancer 25 years earlier.

Case Report

In December 2010, a 72-year-old woman with idiopathic, recurrent pulmonary emboli and a remote history of breast cancer presented with a 10-day history of nausea, dyspnea, dry cough, and dizziness. She had undergone a left radical mastectomy and radiation therapy 25 years earlier. She had never smoked, and she reported no past occupational exposures. She was adhering to her ongoing warfarin therapy. At presentation, she appeared to be ill and in mild respiratory distress. Physical examination revealed a blood pressure of 144/100 mmHg, an irregularly irregular heart rate of 144 beats/min, a respiratory rate of 22 breaths/min, a temperature of 37 °C, and an oxygen saturation of 98% on 4 L of oxygen. She had appreciable jugular venous distention without hepatojugular reflux. She had multiple palpable, calcified, parasternal chest-wall nodules, which had reportedly not changed during the past 8 years. Auscultation revealed clear lungs but distant heart sounds. Laboratory test results showed a hemoglobin level of 11 g/dL, a normal white blood cell count with normal differential, and normal values for platelets, electrolytes, cardiac markers, and liver-associated enzymes. Coagulation values were elevated: the supratherapeutic international normalized ratio (INR) was 4.9. An electrocardiogram showed new-onset atrial fibrillation with a rapid ventricular response rate of 144 beats/min. Chest radiographs showed globular cardiomegaly, which raised suspicion of pericardial effusion (Fig. 1).

Fig. 1 Baseline chest radiograph shows a globular heart, suggesting pericardial effusion.

Chest computed tomography revealed large bilateral pulmonary emboli, small pleural effusions, and nodular pericardial studding with an effusion (Fig. 2). Lower-extremity Doppler ultrasonography did not reveal deep venous thrombosis. Intravenous diltiazem was begun for the patient's atrial fibrillation, and the resultant hypotension responded positively to fluid resuscitation. Transthoracic echocardiography showed a large pericardial effusion with evidence of cardiac tamponade (Fig. 3).

Fig. 2 Chest computed tomography shows A) bilateral pulmonary emboli and B) a large pleural and pericardial effusion.

Fig. 3 Transthoracic echocardiograms. A) Parasternal long-axis view shows a large pericardial effusion (arrows). B) Pulsed-wave Doppler interrogation (apical 4-chamber view) yields >25% variation in E-wave velocity across the mitral valve with respiration, suggesting pericardial tamponade.

The patient was taken to surgery. After reversal of the INR, an inferior vena cava filter was placed. A pericardial window was created, the pericardium was partially dissected, and a pericardial biopsy was performed, with drainage of hemorrhagic fluid. Nodular studding of the pericardium raised suspicion of metastatic breast cancer.

Histopathologic evaluation of the pericardial fluid cell block and pericardial biopsy revealed poorly differentiated, pleomorphic epithelioid cells with high-grade nuclear atypia and mitoses (Fig. 4A). Immunohistochemical studies were positive for calretinin, cytokeratin (CKAE1/AE3, CK7, and CK5/6), and vimentin (Fig. 4B). Melanocyte, breast, lung, and thyroid markers were negative. The diagnosis of primary pericardial mesothelioma was made. There was no radiographic evidence of pleural or peritoneal involvement or other metastasis.

Fig. 4 Photomicrographs show A) poorly differentiated neoplastic cells (H & E, orig. ×200) and B) positive calretinin staining (immunohistochemistry stain, orig. ×200).

With an inferior vena cava filter in place, the patient was discharged from the hospital with instructions to take low-molecular-weight heparin. Treatment options were discussed; after considering the choices and the prognosis, she opted for palliative care. She died 3 months later, and no autopsy was performed. It was not confirmed whether the mesothelioma was histologically limited to the pericardium; however, there was no clinical indication of pleural or peritoneal involvement.

Discussion

Primary pericardial mesothelioma is an exceedingly rare tumor, accounting for less than 5% of all mesotheliomas. In a case series of 120 patients, 75% of the diagnoses were made postmortem, indicating the insidious nature of this highly malignant tumor.³ Its clinical presentation is variable. Symptoms such as orthopnea, cough, and substernal chest pain are nonspecific, and precise diagnosis can be delayed. Our patient had a history of idiopathic venothromboembolism, and we speculate that her recurrent pulmonary emboli and warfarin failure were related to a hypercoagulable state caused by underlying malignancy. However, we have no evidence that the primary pericardial mesothelioma caused the pulmonary emboli in our patient, because an autopsy was not performed. The anticoagulation might have been responsible for the pericardial effusion, at least in part. Constrictive pericarditis may have contributed to venous stasis.

Right ventricular and atrial compression with intracardiac thrombus has been reported.⁴ In one series,⁵ a 14% incidence of pulmonary embolism in malignant mesothelioma was reported. Tumor embolism is less common and seems unlikely in our patient, in that no myocardial invasion was apparent on echocardiography. Cardiac tamponade, a well-known complication of this cancer, is rarely the initial clinical manifestation, but it was in our patient.

Mesothelioma can be localized in the pericardium or it can diffusely encase the heart. It can infiltrate the myocardium, atria, coronary sinuses, coronary arteries, and the conduction system of the heart. Commonly, the diagnosis is made at an advanced local stage; in one study, metastasis to regional lymph nodes or the lungs was detected in 30% to 50% of cases.⁶ The tumor can be diagnosed by means of various imaging methods; magnetic resonance imaging provides comparatively better information about the location and extent of the tumor and helps to determine its resectability. Cytologic analysis of pericardial fluid often yields negative results, so diagnosis usually requires tissue for histologic evaluation after surgery or at autopsy.^1,2

Chemotherapy, including systemic adriamycin, cisplatin, and intracavitary chemotherapy, are of limited success in the treatment of this tumor; however, they may reduce its mass.⁷ Surgical intervention such as pericardiectomy might help cure local tumors, or at least provide palliation by decreasing the disease burden. Rarely can all of the mesothelioma be removed surgically. Nevertheless, survival rates are improved by partial pericardial resection and radiotherapy. The average median survival time of patients with primary pericardial mesothelioma is 10 months after diagnosis.⁸ We found only one instance in which triple-regimen therapy was used to treat primary pericardial mesothelioma.⁹ The therapy—cisplatin 40 mg/m², gemcitabine 800 mg/m², and vinorelbine 20 mg/m² in 4 cycles—enabled the patient to remain disease-free for 24 months after final chemotherapy without any evidence of disease progression. Lovastatin, a cholesterol-reducing drug, inhibits cell growth, induces apoptosis, and reverses doxorubicin resistance in malignant mesothelioma. It has not been thoroughly studied, but it may serve as a basis for adjunctive treatment of patients with mesothelioma.^10,11

Newer approaches to fighting cancer hold promise and are being studied in application to mesothelioma.¹² These include anti-angiogenesis drugs, which target the blood supply of the tumor while sparing normal cells and tissue; biologic response modifiers, which might make cancer cells more susceptible to destruction by the body's own immune system; photodynamic therapy, which relies on use of a photosensitive drug that concentrates within diseased tissue, application of laser light through a thoracoscopic surgical approach, and activation and killing of the cells in which the drug is concentrated; and gene therapy, whereby lost or mutated genes can be delivered to the diseased cells through vectors that integrate into the host's DNA. All of these therapies are being tested in clinical trials, imparting some hope of future treatment options for primary pericardial mesothelioma, a highly fatal disease.

Acknowledgment

We thank Frank C. McGeehin, MD, for his assiduous efforts in the management of our patient.