Cardiac Tumors

The patient was a 34 year old African American woman, HIV negative, smoker (one pack per day for 20 years), asthmatic, with a history of positive PPD and tuberculous infection, treated with 4 antituberculous medications. As part of the work-up a CT scan of the chest was done, which revealed a large mass involving the middle and lower lobes of the right lung. In addition, a bronchial washing was reported positive for adenocarcinoma, and subsequently she underwent right pneumonectomy. The right lung as well as the mediastinal lymph nodes were involved by a moderately to poorly differentiated adenocarcinoma. Moreover, the lung showed focal emphysematous changes and several 0.5 cm arteriovenous malformations. After the operation she returned to work, but came back to the ER twice complaining of dyspnea and productive cough with yellow sputum. Jugular venous distension was absent and left breath sounds were clear. She was treated with albuterol and discharged on prednisone (20mg qd x 5 days). She then experienced increasing shortness of breath and the emergency medical service was called. The paramedics found her able to talk, but soon thereafter, she lost consciousness, suffered a cardiac arrest and died on her way to the hospital.

Gross Description
The body was that of a thin, well-developed woman measuring 168 cm and weighing 62 kg. The skin was unremarkable except for a right thoracotomy scar. Upon opening the chest, the mediastinum was noted shifted to the right side. The right border of the heart was 10 cm from the right lateral chest wall. The posterior aspect of the right thoracic cavity was occupied by scar tissue, and the anterior portion was filled with clotted blood and fibrin. The left lung was expanded. Multiple lymph nodes were present in the mediastinum, the largest being 3 cm in maximal dimension. The left lung weighed 500 g. The pleural surfaces were smooth and shiny. On section, the parenchyma revealed an area of increased firmness and hemorrhage in the lower lobe, measuring 5 cm in greatest dimension, extending to the visceral pleura. In addition, there was a moderate loss of parenchyma with formation of smooth-lined cysts of up to 0.5 cm in diameter. These cysts were present in both lobes throughout. The larynx, trachea, major and segmental bronchi were of average caliber. Organizing emboli measuring up to 3 mm occluded small branches of the pulmonary artery.

The heart was 240 g and of the expected shape. The parietal pericardium was smooth and glistening. The sac contained approximately 500 cc of serosanguineous fluid. The epicardium was thickened, dull, firm and white in a few areas with multiple hemorrhagic foci of up to 0.2 cm (Figure 1). The atria were normal and free of thrombi. The foramen ovale was closed. The right and left ventricular walls measured 0.4 cm and 1.2 cm in thickness, respectively. The valve rings measured as follows: tricuspid valve 12 cm, pulmonic valve 7 cm, mitral valve 8.5 cm, and aortic valve 6 cm. The valve leaflets were pliable and the chordae tendineae were thin and slender. The myocardium and endocardium were  unremarkable. The coronary arteries were of normal caliber and distribution. The aorta showed mild atherosclerosis in the abdominal portion.

 

Figure 1 Cross section of the heart showing metastatic carcinoma involving the epicardium with focal invasion of the myocardium (arrow)

The liver weighed 1400 g and was of normal size and shape. The cut surface showed marked acute centrilobular congestion and multiple tan, firm nodules measuring 0.2 to 0.4 cm. The lobular pattern was preserved otherwise. The remaining organs had no significant pathologic changes.

Microscopic Description
Sections from the epicardium showed many single and small clusters of poorly differentiated carcinoma cells, near the epicardial surface. Some of these cells contained vacuoles consistent with mucin droplets of adenocarcinoma. The malignant cells were large with pleomorphic nuclei and prominent nucleoli. Some were present within lymphatics. Metastatic carcinoma was present bilaterally in hilar lymph nodes. The firm, hemorrhagic areas in both lobes of the left lung corresponded to foci of hemorrhagic infarcts. Surrounding arteries contained numerous acute, organizing and recanalized thrombi. The tan nodules present in the liver did not represent metastatic adenocarcinoma but rather foci of adenomatosis. They were composed of thickened cords of hepatocytes separated by sinusoids and devoid of portal tracts, bile ductules or scars.

Case Analysis
The heart can be involved by primary as well as metastatic tumors. Primary tumors of the heart are rare (< 0.3 % in postmortem series), with myxoma the most frequent. Metastases from neoplasms arising in other organs are far more common and include carcinomas, sarcomas, hematologic malignancies and melanoma. Nonetheless, cardiac metastases are infrequent. Why is the heart relatively protected from metastasis? Possible explanations include the continuous forceful stroke of the heart, rapid blood flow and afferent lymphatic circulation. If these hypotheses were true, cardiac tumors would be present almost invariably in patients with previous cardiac damage with reduced pump action and blood flow, but there is no such confirmatory data in the literature. Regarding afferent lymphatics, metastatic dissemination in the heart occurs most commonly through lymphatic invasion. Overall, the heart is probably protected as a result of the combination of all these and other unknown factors. Moreover, tumor type, metabolic properties of the heart, and adhesion molecules among others, are under consideration and require further investigation.

Secondary tumors may involve the heart by direct extension, hematogenous spread or lymphatic dissemination. Direct extension occurs from tumors arising in the lungs or mediastinum (i.e. bronchogenic and esophageal carcinoma, malignant thymoma, thymic carcinoma). Hematogenous spread is often seen with sarcomas (e.g. uterine. leiomyosarcomas can reach the heart through the inferior vena cava), leukemia, multiple myeloma, and with certain types of carcinoma (e.g. hepatocellular carcinoma). However, the lymphatic pathway appears to be the most significant. This is demonstrated by the frequent metastatic involvement of the pericardium, richly supplied by lymphatic channels that drain in the anterior and posterior mediastinum. In the present case, the patient had a history of adenocarcinoma of the lung involving mediastinal lymph nodes; therefore, it is not surprising that she presented with a pericardial effusion and associated cardiac tamponade. Pericardial involvement in a patient with a known primary malignancy, should be suspected in the setting of pericardial effusion, intractable heart failure or hepatomegaly in the absence of metastatic lesions. The differential diagnosis includes congestive heart failure in a patient with a cardiomyopathy, and nonmalignant pericardial effusions (infectious and non-infectious). This patient was young, with no history of heart disease. Although she had asthma in the past and evidence of chronic obstructive pulmonary disease as per the autopsy exam, she did not have pulmonary hypertension or cor-pulmonale.

Tuberculous (TB) pericarditis is a consideration based on her prior history of PPD positivity and antituberculous treatment. TB pericarditis may develop insidiously, or acutely with a large effusion and cardiac tamponade, particularly in immunosuppressed patients. She was HIV negative and had not been treated with chemotherapeutic agents. If she had lived, the diagnosis of malignant pericardial effusion could have been made with a pericardiocentesis and cytologic examination of the fluid. Adenocarcinoma cells are readily identified in pericardial fluid by their tri-dimensional arrangement, distinct cell borders, high nuclear-cytoplasmic ratio and prominent nucleoli (Figure 2). They must be differentiated from reactive mesothelial cells, which is not often easy. Reactive mesothelial cells, especially in long-standing effusions can also exhibit a glandular arrangement, prominent nucleoli, mitotic figures and even vacuolization that mimic adenocarcinoma. Immunohistochemistry is useful in distinguishing the two. Both cell types are immunoreactive to cytokeratin, but only adenocarcinoma stains with the adenocarcinoma marker B72.3 and carcinoembryonic antigen (CEA).

 

Figurea 2 Pericardial fluid containing adenocarcinoma cells. The malignant cells have a finely vacuolated cytoplasm, irregular nuclear contours and prominens nucleoli (Papanicolaou, 60x).

Pulmonary adenocarcinoma arises preferentially in the periphery of the lung parenchyma. Central lesions may occur, but are less frequent. This type of tumor can develop in smokers as well as in non-smokers, de novo or in areas of pre-existing scarring. Our patient was a smoker for 20 years. Although she had a risk factor for lung cancer, the aggressive behavior of this tumor (stage T2, N2 at initial diagnosis) suggests a genetic predisposition.

The advent of cardiovascular imaging studies has improved the diagnosis of cardiac involvement by metastatic disease, but the prognosis remains poor. In a recent study done at the Tottori University School of Medicine in Japan, 46 of 161 patients had secondary cardiac tumors diagnosed by echocardiography. The most common primary site was the lung followed by mediastinum, liver, uterus and testis. Forty seven percent of the cases had pericardial involvement, 32% involved the right side of the heart and 14 % involved the left. Metastases on both sides of the heart were noted in 7% of cases. It is unknown why intracavitary lesions are less common, but there is evidence that certain tumors have predilection for this pattern of growth (Figures 3 and 4). In our experience, squamous carcinoma arising in different sites has the tendency to invade and seed cardiac valves, endocardium and myocardium. Prior valve damage or endothelial damage appears to be a sine qua non in such cases. As a result, death can occur due to arrhythmia with or without conduction system involvement and embolization. Changes in the electrocardiogram such as prolonged elevation of the ST segment are indicative of myocardial invasion.

 

Figure 3 Echocardiogram showing an intracavitary right ventricular mass in a patient with lymphoma (circle and arrow)

 

Figure 4 Transverse section of the heart showing an intracavitary right-sided mass (arrow) and patchy involvement of the myocardium by a fleshy, hemorrhagic tumor. the patient had been diagnosed with Non-Hodgkin's lymphoma.

In the present case, the patient died of Cardiac tamponade due to a malignant pericardial effusion. In addition, she was in a hypercoagulable state with numerous acute and organizing pulmonary emboli leading to areas of hemorrhagic infarction. Her symptoms of dyspnea and shortness of breath were related to both the pulmonary embolism and evolving cardiac tamponade. Of note, dyspnea is the most common manifestation of Cardiac Tumors in general, and is suggestive of cardiac decompensation. Treatment is palliative, aimed at controlling effusions, arrhythmia and heart failure. Radiotherapy is the treatment of choice to manage malignant effusions. In some instances, a pericardial window is required to treat tamponade. Chemotherapy has been used to prevent further cardiac involvement, but its use is limited by its cardiotoxicity. In rare instances, surgical debulking is indicated to alleviate obstructive cardiac masses.

Posted in: Cardiac Tumors