Metastatic cardiac tumors: from clinical presentation through diagnosis to treatment

A patient in the 5th decade with history of metastatic malignant melanoma performed a periodic follow-up positron emission tomography CT. During the 7 years since the diagnosis, the patient experienced 4 recurrences of metastatic tumors that were all resected and followed by various modes of immunotherapy (interferon-alpha and tumor infiltrating lymphocytes). A scheduled positron emission tomography CT demonstrated a mass in the right atrium (Fig. 1 Im). No other metastatic lesions were identified. Echocardiography showed right atrium mass. There was normal function of the ventricles and valves and no evidence of a pericardial effusion. Transesophageal echocardiogram verified that the atrial mass was pedunculated and surgical intervention proceeded. A mass measuring 3.5 × 4 × 4.5 cm was resected from the right atrium. The mass presented histomorphological features of malignant melanoma and was attached to the myocardial wall (Fig. 1 H, large lesion, representative samples were examined.). A year later, a single brain metastasis was removed by radiosurgery and the following year the patient commenced a long-term B-Raf inhibitor treatment with Vemurafenib (Zelboraf). After five years of follow up the patient is alive with no symptoms.

A patient in the 7th decade was admitted with clinical presentation of superior vena cava syndrome. During the two weeks prior to the admission the patient developed a cough, dyspnea, facial edema and deterioration in functional ability. Positron emission tomography CT (Fig. 2 Im) demonstrated a hypermetabolic mass in the right atrium protruding into the superior vena cava. Eleven months before, a right adrenalectomy and right hemicolectomy were performed due to poorly-differentiated adenocarcinoma. Although surgical resection of the cardiac mass was considered, the patient’s general condition did not allow this intervention. The patient died after a week of hospitalization, during which hemodynamic instability necessitated mechanical ventilation. On the autopsy performed, a mass measuring 6 × 6 × 3 cm was found attached to the right atrium wall, morphologically compatible with poorly differentiated adenocarcinoma (Fig. 2 H, large lesion, representative samples were examined.). Additional findings included disseminated metastatic adenocarcinoma involving the lung, left adrenal, liver, thyroid and numerous lymph nodes.

A patient in the 8th decade presented with hemoptysis. Echocardiography showed ejection fraction of 65%, hypertrophic septum with no metastatic involvement and a small pericardial effusion. Moderate aortic stenosis with moderate aortic regurgitation were also detected. A CT scan demonstrated a lung mass in the left hilum and a cardiac CT and cardiac magnetic resonance imaging (MRI) demonstrated involvement of the interventricular septum (Fig. 3 Im). The lung mass biopsy showed a basaloid squamous cell carcinoma, positive for the neuroendocrine immuno-marker CD56 (Fig. 3 H, endobronchial biopsy - all material was submitted for histologic examination). The patient’s clinical presentation was dominated by his primary lung malignancy and cardiac surgery was not indicated. The patient died 9 months after the lung cancer diagnosis, due to his primary malignancy.

The next case exemplifies the clinical mimickers of MCTs and the differential diagnosis.

A patient in the 4th decade with a known metastatic testicular high-grade non-seminomatous germ cell tumor was admitted due to a cardiac mass (Fig. 4 Im) that was discovered during a routine follow-up CT. At first presentation, 6 years earlier, the patient had massive involvement of the liver and retroperitoneum that was treated with orchiectomy and chemotherapy and later, with retroperitoneal lymph node dissection and left nephrectomy. Following, the patient developed liver metastases that relapsed after surgical resection, and was given several courses of chemotherapy. At admission, the patient had 3 small metastases in both lungs and few metastases in the liver. In addition, a mass that involved the hepatic vein and the inferior vena cava, the latter of which extended into the right atrium. Despite these findings and all the treatments given so far, the patient remained functional with well-preserved liver, renal and pulmonary function. Echocardiography recorded a right atrium mass, a 40% ejection fraction and normal size and function of the ventricles and valves. A collaborative team of cardiac and hepatobilliary surgeons resected both the cardiac and liver masses. The liver mass was diagnosed as unclassified epithelioid malignant tumor. However, the polypoid right atrium mass that measured 2.5 × 2.5 × 4.5 cm was concluded as a thrombus (Fig. 4 Im, all the material was submitted for histologic examination). Eleven months later, the patient succumbed to his primary malignancy due to hepatic failure.

From the Serbian patient population, four died within a period of 1–16 months postoperatively. One patient with metastatic uterine leiomyosarcoma is still in the early postoperative period and is currently recovering from the operation.

Tumors spread can occur, in descending order, to the pericardium, myocardium (Fig. 3 Im), epicardium, endocardium and less frequently to the intracavitary regions with predominance to the right-side of the heart (Figs. 1 Im and 3). Possible pathways for cardiac tumor spread are:

The clinical manifestations of MCTs are nonspecific and depend on their location. There is no strong correlation between extent of cardiac involvement and the clinical manifestation [15]. Most secondary tumors of the heart are clinically silent (over 90%) [1], and are often diagnosed only postmortem. Therefore, early detection of these tumors is extremely challenging. At the time of initial tumor staging, metastases of the heart are usually not detected. Typically, cardiac metastases remain clinically silent until many years after cancer diagnosis. For example, cardiac metastases of malignant melanoma have been reported 14–22 years after the initial diagnosis [16, 17]. Thus, if oncologic patient presents with new onset of cardiac symptoms, clinicians should be aware of the possibility of cardiac metastases and perform further investigations [18].

MCTs may present with a wide spectrum of common cardiac symptoms and signs, but usually they present with right-sided heart failure. Symptoms attributed to arrhythmias can be seen and are due to invasion of the cardiac conduction system [19]. MCTs can also mimic cardiac ischemia due to invasion, compression or embolism of coronary arteries [20]. A life-threatening manifestation can occur when cardiac tamponade from pericardial involvement is present.

To date, there are no physical or laboratory examinations that specifically detect cardiac metastases. Nevertheless, the timely identification of patients with cardiac metastases is of outmost importance for the effectiveness of therapy. None of the signs of cardiac metastases are specific. Therefore, physical examinations can detect various murmurs and electrocardiogram can document diverse changes but imaging studies play a key role in the diagnosis.

Chest radiography may demonstrate cardiomegaly with “water bottle” sign or an enlarged azygos vein if pericardial effusion is present [21]. Yet, echocardiography remains the most efficient method for initial diagnosis. It assesses clinical signs and symptoms of heart failure, detects cardiac masses and pericardial effusion and provides information on the location, size and mobility of cardiac masses.

Supplemental diagnostic imaging methods are computed tomography, positron emission tomography CT and magnetic resonance tomography that add information on the tumor size and morphology, location, invasiveness, and vascularization. These methods provide sections of cardiac, mediastinal, pulmonary and thoracic structures in any plan without overlapping. Administration of contrast may be of help, with F-fluorodeoxyglucose, positron emission tomography CT scan identifying tumors that exhibit increased metabolism using glucose, which help to differentiate malignant from benign tumors. (Fig. 1 Im) [20, 22].

The differential diagnosis for cardiac metastases includes thrombi, as exemplified by Case No.4, vegetations, which are the most common causes of cardiac masses [20] and primary cardiac tumors such as myxoma.

Pericardioscopy allows inspection of the periocardium and epicardium and permits tissue acquisition. Pericardioscopy, as a diagnostic tool, is especially powerful in assessment of pericardial disease of unknown origin, [23] particularly when combined with pathological and molecular methods. However, the technique is quite demanding and can be performed only in a limited number of experienced tertiary referral centers.

Cytological evaluation of pericardial effusion can identify malignant cells. About 24% of all cases assessed by pericardial fluid cytology are attributed to malignancy [24]. The leading cause for pericardial effusion is lung adenocarcinoma followed by breast carcinoma in women. Cytology is superior to pericardial biopsy in diagnosing metastatic carcinoma (14.7% false-negative rate for cytology vs., 40% for pericardial biopsy). Other tumors may go undetected in the pericardial fluid. There is no available data on the association of MCTs with pericardial effusion.

Pathological evaluation remains the most definite method for differentiating neoplastic from non-neoplastic cardiac masses [20]. While preoperative diagnostic cardiac biopsies are rarely performed, postoperative pathological evaluation following resection of these tumors, are always performed regardless of their nature.

Clinical presentation will define the most appropriate management modality. As cardiac metastases are seen in patients with advanced malignant disease, many patients will have already undergone surgical treatment or receive radio/chemotherapy for the original tumor. For the majority of patients, the goal of the treatment is to provide palliation of the symptoms and prevent tumor recurrence.

Cardiac tamponade necessitates immediate pericardiocentesis followed by local administration of chemotherapeutics or radioisotopes to prevent recurrence [15]. If life threatening arrhythmias are detected, they will be the focus of the treatment, including radiofrequent ablation for uncontrollable arrhythmias [25]. In selected cases, chemo embolization of coronary arteries supplying a single cardiac mass may be effective [26].

MCTs present a particular challenge for heart surgeons and need to be treated in specialized cardiac centers that have experience over the whole spectrum of heart surgery. Owing to the small numbers of cases, there are no evidence-based guidelines for the optimal treatment regimen; nevertheless, surgical management should be considered in individual cases. Surgery may be critical and represents the treatment of choice in cases in which prognosis is good, when there are no other metastatic sites, and the tumor can be removed in toto or in cases of poor expected outcome if intra-cardiac obstruction is present [27]. Following, adjuvant radio/chemotherapy should be employed. Because of the multi-modalities of treatment, a multidisciplinary team of cardiologist, oncologist and cardiothoracic surgeon, working with the patient, should contribute to the therapeutic decision-making process. Case No. 1 gives an exceptional example to the effectiveness of multidisciplinary team-work which combines surgery with radio/chemotherapy and cutting edge biological treatments and targeted medications.