Case Report

A 76-year-old man was noted to have elevated liver function values during a routine medical checkup. He was a nonsmoker with a history of insulin-dependent diabetes mellitus. His job as an electrician placed him at high risk for asbestos exposure, but there was no known specific exposure and no information about whether a BAP1 mutation was present. He had no chest pain, dyspnea, or peripheral edema. Further laboratory testing revealed elevated cardiac enzymes, and echocardiography showed a dilated left ventricle (end-diastolic dimension, 58 mm), moderately reduced ejection fraction (36%), and a motion abnormality in the anterior wall of the heart (Fig. 1A).

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The patient was diagnosed with congestive heart failure (HF) and admitted to the hospital, where chest computed tomography (CT) revealed a tumor measuring 35 mm × 78 mm extending from the left atrial appendage to the left pulmonary artery. A small pericardial effusion was present, and the mediastinal lymph nodes were enlarged (Fig. 1B). There was no pleural calcification or pleural effusion. Contrast-enhanced magnetic resonance imaging of the chest showed high intensity on T1-weighted images just above the left atrium, with thinning of the myocardium from the anterior wall to the anterior septum. Myocardial perfusion single-photon emission CT demonstrated decreased blood flow in the region of the left anterior descending (LAD) coronary artery. Fluorodeoxyglucose (FDG) positron emission tomography showed abnormal uptake of FDG around the left atrium (diameter, 70 mm) and in a mediastinal lymph node (Fig. 1C). There was no evidence of metastasis or of a different primary tumor (Fig. 1D). Coronary CT showed compression causing 90% stenosis at the origin of the LAD, without calcification (Fig. 2).

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The patient was discharged from the hospital after testing was completed; he remained asymptomatic. Three months later, outpatient contrast-enhanced CT showed that the tumor had grown by approximately 5 mm and was infiltrating the surrounding area of the heart; malignancy was suspected, with hemangiosarcoma and malignant lymphoma included in the differential diagnosis based on the imaging findings. Elevated blood levels of soluble interleukin-2 receptor (1,120 U/mL) supported the possibility of malignant lymphoma. At this point, the possibility of a primary pericardial malignancy was not considered.

The patient was referred to the treating hospital for surgical intervention. On arrival, his vital signs were stable, and physical examination showed no abnormalities. Laboratory testing revealed normal liver function but uncontrolled diabetes mellitus (hemoglobin A_1c, 8.4%) and active inflammation (C-reactive protein, 8.35 mg/dL). Electrocardiography revealed abnormal Q waves on leads V₁ through V₃, left anterior fascicular block, and complete right bundle branch block. No abnormalities were seen on chest radiography (cardiothoracic ratio, 54.5%). Transesophageal echocardiography demonstrated impaired left ventricular function (ejection fraction, 36.3%) and a dilated left ventricle (end-diastolic dimension, 67.8 mm) and left atrium (diameter, 41.5 mm). A tumor was observed extending from the ascending aorta and encircling the left pulmonary artery and the lateral wall of the left ventricle. No thrombus was noted in the left atrial appendage. The left main coronary artery was absent; the LAD and left circumflex artery had anomalous origins in the sinus of Valsalva.

Because percutaneous coronary intervention in a patient with anomalous coronary arteries is difficult, the surgeons initially planned to perform coronary artery bypass grafting and tumor resection through a median sternotomy. However, the possibility of infection with uncontrolled diabetes mellitus and the difficulty of resecting a tumor exhibiting myocardial infiltration prompted a revised approach. The surgeons decided to perform MID-CAB with a tumor biopsy, with postoperative chemotherapy and radiation pending the pathology results.

Technique

The surgery was performed via a left fifth intercostal thoracotomy. The left internal thoracic artery (LITA)-to-LAD anastomosis was completed without any difficulty, but the field of view during MID-CAB was so narrow that the surgeons could not visualize the entire tumor and were unable to identify the enlarged lymph node because of dense adhesions. Thus, the lymph nodes could not be sampled and only the pericardium was biopsied. Frozen section examination during the operation of the pericardium biopsy revealed atypical epithelial cell proliferation and fatty tissue infiltration suggestive of malignancy. Histopathologic evaluation of a pericardial biopsy revealed proliferation of epithelioid cells with acidophilic cytoplasm and atypical nuclei (Fig. 3A). Immunohistochemical staining was strongly positive for calretinin (Fig. 3B), cytokeratin, D2-40, and WT1. The final diagnosis was malignant pericardial epithelioid mesothelioma.

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Discussion

Although PMPM is extremely rare, with an incidence of less than 0.0022%, it accounts for up to 50% of primary malignant pericardial tumors^1,2 and is the third most common primary malignant cardiac tumor, after hemangiosarcoma and rhabdomyosarcoma.^3,4 Because it was not possible to determine the origin of this patient's tumor from the imaging studies, the differential diagnosis included primary cardiac malignant tumors and metastatic lesions from primary cancers including lymphoma, melanoma, or lung cancer. It was not possible to reach a definitive diagnosis without pathologic examination of tissue.

The clinical manifestations of pericardial mesothelioma are constrictive pericarditis, pulmonary embolism, cardiac tamponade, and HF caused by myocardial infiltration.^3,5 The most common causes of death are cardiac tamponade and HF.² However, nonspecific symptoms and long asymptomatic periods make early, accurate diagnosis difficult⁶; only 25% to 30% of patients are diagnosed before death.^3,7,8 In this asymptomatic patient, the tumor was found incidentally on CT scan, but the tumor invasion was advanced; this finding is consistent with those of previous studies showing a poor prognosis once PMPM is discovered. The median survival time from symptom onset is reportedly 3 to 11 months.^2,9

The diagnosis of PMPM is challenging. The lack of characteristic imaging findings, low prevalence, and nonspecific symptoms mean that pathologic diagnosis is typically required. Primary malignant pericardial mesothelioma can occur as a local solid tumor, a plaque-like thickening, or a diffuse infiltrate in the pericardium and adjacent structures, as in this patient. Pleural calcification is characteristically seen on imaging with pleural mesothelioma, but primary calcification in PMPM is not typical.¹⁰

Currently, no standard treatment for PMPM exists; however, surgery, chemotherapy, and radiation are commonly used as palliative therapy. Surgery plays a limited role in PMPM because of the high mortality associated with this tumor. Tumor resection is effective if the tumors are minimally adherent and localized; long-term survival is expected for patients in whom total resection is possible. However, this is a rare situation because few patients have resectable tumors at diagnosis. The most frequently used techniques for patients with advanced PMPM are palliative surgery and pericardiectomy for palliation of symptoms. A pericardial window can be helpful for delivering chemotherapy.^5,11

There are no previous reports of MID-CAB being used to treat coronary artery stenosis caused by PMPM or other cardiac tumors. Although asymptomatic, the patient in this report had mild congestive HF and a cardiac mass of unknown etiology. The decision to perform surgery was the correct one. Opinions vary on using bypass for coronary stenosis caused by PMPM, which has a poor prognosis. In this case, because of the fast growth of the tumor, myocardial ischemia could occur before chemotherapy and radiation therapy could be administered; therefore, bypass grafting was indicated. Although a tumor biopsy was considered, a medial sternotomy would put this patient at high risk for postoperative mediastinitis because of his uncontrolled diabetes. In addition, the results of the preoperative examinations indicated that the tumor was highly adherent and would be difficult to resect. In fact, the narrow field of view during MID-CAB did not allow the full extent of the tumor to be visualized, and resection was impossible because of the dense adhesions. Adequate preparation for tumor resection will be required if the surgeons encounter similar patients in the future. However, given that total tumor resection is difficult for advanced-stage PMPM—and that most patients present with advanced PMPM—minimally invasive treatment, such as MID-CAB, may be reasonable and effective as palliative treatment.

Conclusion

Although PMPM is an extremely rare and highly malignant tumor, the patient in this report was able to undergo effective and safe treatment of the resultant coronary artery constriction with MID-CAB. Optimal treatment for PMPM remains controversial, but minimally invasive approaches, such as MID-CAB, may be used as palliative therapy. More patients need to be studied to provide further validation of our findings.