Continuing Education Activity

Cardiac tumors are uncommon and can be primary or metastatic. Primary cardiac tumors are rare, and the incidence is from 0.001 to 0.3% by autopsy. They can be classified into three clinicopathological groups: 1. benign congenital tumors; 2. benign acquired tumors; and 3. malignant tumors. Nearly 90% of primary cardiac tumors are benign. This activity reviews the etiology, pathophysiology, presentation, and treatment options of cardiac tumors and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the different types of cardiac tumors and their etiologies.
• Discuss the histopathology of the different types of cardiac tumors.
• Summarize the evaluation process and diagnostic testing for the assessment of cardiac tumors.
• Review the importance of improving care coordination among interprofessional team members to improve patient outcomes affected by cardiac tumors.

Introduction

Cardiac tumors are uncommon and can be primary or metastatic. Primary cardiac tumors are rare, and the incidence is from 0.001 to 0.3% by autopsy.[1] They can be classified into three clinicopathological groups: 1. benign congenital tumors; 2. benign acquired tumors; and 3. malignant tumors. Nearly 90% of primary cardiac tumors are benign. Myxoma is the most common primary tumor of the heart, accounting for slightly more than half of all primary cardiac tumors.[2] Malignant cardiac tumors are rare and account for 10% of all primary cardiac neoplasms. They include sarcomas, especially angiosarcomas. Tumors that metastasize to the heart are much more common than primary cardiac tumors but are rarely surgically excised.

Etiology

Some cardiac tumors occur in the setting of genetic predispositions or are part of genetic syndromes; this may have implications for genetic counseling and therapeutic implications for targeted therapies.

• Cardiac rhabdomyomas correlate with tuberous sclerosis, an autosomal dominant disorder characterized by the development of hamartomas in multiple organs.[3]
• Cardiac fibromas may correlate with Gorlin syndrome, an autosomal dominant disorder characterized by developmental abnormalities and a predisposition to neoplasia.[4]
• Cardiac myxomas may be part of the Carney complex, an autosomal dominant syndrome.[5]
• Histiocytoid cardiomyopathy sometimes occurs in families, but the exact genetic abnormalities are unknown.[6]
• The genomic profile of most cardiac undifferentiated sarcomas is like that of pulmonary artery intimal sarcomas with recurrent alterations in MDM2, PDGFRA, and CDKN2A genes.[7]
• Papillary fibroelastomas have been reported after cardiac instrumentation and thoracic irradiation.[8]

Epidemiology

Primary cardiac tumors are much rarer than secondary malignant lesions occurring in about 0.001 to 0.3% of the autopsies. Almost 90% of primary cardiac tumors excised surgically are benign. Until recently, cardiac myxomas had wide recognition as the most common primary benign cardiac neoplasm of adulthood, representing nearly 80% of benign tumors. Secondary malignant disease of the heart and pericardium is considerably more common than primary cardiac malignant disease; in some estimates, it is 30 to 1000 times more common. In a random autopsy series, the frequency of metastatic involvement was 0.4%; in patients with confirmed cancer, cardiac involvement can be as high as 20%. Spread to the heart is generally via direct tumor extension, venous/lymphatic spread, or arterial metastasis. The most common underlying malignant diseases with secondary cardiac involvement are carcinoma of the lung, breast, esophagus, stomach, kidneys, melanoma, lymphoma, and leukemia.

Histopathology

Primary Cardiac Tumors

Benign Tumors

1. Myxoma

• The most common benign tumor in adults. More frequently found in the left atrium (80%), followed by the right atrium and occasionally in the ventricles. 
• They characteristically arise around the interatrial septum next to the fossa ovalis membrane.
• They are more common in women and often appear in the sixth decade of life.
• The majority of the cardiac myxomas are sporadic but familial cases have been described.
• Macroscopically, two basic gross subtypes have been described: solid and villous. Tumors of the solid type may be globular or elongated, with a smooth, shiny, and sometimes undulant surface. Tumors of the villous type have irregular, often friable papillary surfaces.[9]
• Histologically, the one defining characteristic is the presence of the so-called myxoma cell (or lepidic cell), a cytologically bland cell with eosinophilic cytoplasm and an oval or round nucleus. These stellate, ovoid or plump spindle cells may occur singly or in groups. The cells are typically within a myxoid matrix rich in mucopolysaccharides. Large thick-walled vessels are often present near the stalk or the base of the lesion.
• Due to the lack of strong structure, embolization is common.[10]

2. Lipomas

• The second most frequent primary cardiac mass. Represent 0.5% of cardiac tumors
• More frequently present in the sub-endocardium and sub-epicardium of the left ventricle, right atrium, or interatrial septum[11]
• Macroscopically, lipomas are yellow, soft, smooth, well-circumscribed, encapsulated solitary masses.
• Microscopically, the tumors consist of white fat with a fibrous capsule and some fibrous septa; the fat cells have minimal to no atypia.
• Lipomas are mostly asymptomatic, but depending on their location, they can produce arrhythmias or conduction system disease and heart failure symptoms.

3. Papillary fibroelastoma

• Also known as endocardial papilloma
• Most frequent tumor of the valves (75%) with the most common location in the aortic valve followed by the mitral valve
• Derived from the endocardial cells; 95% found in the left-sided chambers
• More common in men and diagnoses at 6th to 7th decade of life
• Macroscopically, papillary fibroelastomas often have a round, whitish appearance and soft consistency. When placed in solution, multiple delicate fronds unfurl, giving the tumor a "sea anemone-like" appearance. The tumors range from 2 to 50 mm and are usually attached to the endocardium by a single stalk.[12][13]
• Microscopically, papillary fibroelastomas consist of narrow avascular papillary fronds that often exhibit complex branching patterns. Histologically, the collagen and elastic fiber arrangement are reminiscent of the tendinous cords of the atrioventricular valves.
• Embolization is common. Valvular insufficiency or obstruction are also present. Heart failure symptoms and a new murmur in the physical exam are also typical findings. 

4. Rhabdomyomas

• The most common cardiac tumor in children often occurring before the first year of life. Over 86% of cardiac rhabdomyomas have been reported in association with tuberous sclerosis.[14]
• It can be multiple and most commonly affects the ventricles. 
• Macroscopically, rhabdomyomas are well-defined, unencapsulated, whitish, or grayish nodular masses that range in size from millimeters to several centimeters.    
• Microscopically, rhabdomyomas are well-demarcated nodules of enlarged vacuolated cells with clear cytoplasm because of glycogen deposits. A characteristic feature is the so-called spider cell appearance. 
• Symptoms are secondary to obstruction of the cardiac chambers and conduction system disturbance as heart block or ventricular tachyarrhythmias.[15]
• Most of these tumors regress spontaneously after birth, and resection is rarely necessary, except in cases of obstruction or arrhythmias.

5. Fibromas:

• The second most frequent cardiac tumor found in childhood, with a slight male predominance.
• Are intramural tumor, mostly in the left ventricular, septum 
• Macroscopically, cardiac fibromas are well-circumscribed, firm, usually solitary white masses grossly resembling fibromatosis or uterine leiomyomas. Their appearance on cut section is typically whorled.
• Microscopically, cardiac fibroma is composed of monomorphic fibroblasts that demonstrate little or no atypia. The margins infiltrate into the cardiac muscle.[16]
• The signs and symptoms correlate with heart failure symptoms, increase the risk of ventricular tachyarrhythmias, and sudden cardiac death.

Malignant Tumors

Cardiac Sarcomas

Angiosarcoma

• Most common primary malignant tumor with an increasing incidence in the fourth decade of life.
• The right atrial chamber is the most frequent location
• Macroscopically, angiosarcomas are typically dark brown or black hemorrhagic masses with infiltrating borders. 
• Microscopically,  angiosarcoma typically infiltrates cardiac muscle without distinct margins. The vascular channels are irregular, anastomosing, and sinusoidal, with pleomorphic lining cells showing frequent mitotic figures.[17]
• The prognosis of patients with angiosarcoma is poor.

Secondary Cardiac Tumors

• Metastatic involvement of the heart is frequent, and this may come from the direct invasion of the tumor from the mediastinum or hematogenous spread.[18]
• Suspicion for cardiac metastasis or tumor extension needs clarification in patients with new findings suggestive of heart failure or valvular disease.
• Pericardial effusion is one of the most common findings in patients with malignancy extending to the heart.
• Histologically the cardiac mass will be determined by the underlying malignancy causing the cardiac tumor.

History and Physical

The clinical symptoms of different cardiac tumors are often non-specific and insidious, which can delay diagnosis and surgical management. The symptoms may relate to processes in the heart, such as valvular dysfunction, pericardial effusion with tamponade, intracardiac blood flow obstruction, arrhythmia, and congestive heart failure. An increasing proportion of cardiac tumors induce no symptoms and become obvious only as an incidental finding.[19] The clinical manifestations depend on the tumor's size, anatomical location, growth, and invasiveness.[19]

Evaluation

Multiple imaging modalities can be useful to determine the mass characteristics and origin. Ultimately, due to the complexity of histological evaluation of cardiac masses, most of these tumors, unless removed, will not be diagnosed with certainty.

The following imaging techniques are mostly used to determine cardiac masses:

Echocardiogram

EKG is an important imaging technique that is likely to be the one that makes the diagnosis of the cardiac tumor. Sensitivity and specificity are as high as 90% 

It can be performed easily at the bedside, and if further detail is necessary, the use of transesophageal echocardiogram can help to determine further characteristics and location of the cardiac tumor.

This modality can determine, size, mobility, and extension of the tumor and relation with neighboring structures and to determine dynamics relates to the mass as obstructions or valvular insufficiency.

The use of transesophageal echocardiogram can also increase the visualization of small tumors not clear in the transthoracic echocardiogram.

Contrast echocardiography is also useful to differentiate between cardiac tumor versus cardiac thrombus.

Three-dimensional echocardiography is an additional feature to determine the dimensions, shape, and structural involvement of the tumor.

Cardiac MRI

Cardiac MRI an excellent imaging modality to determine tumor size, location, adjacent structures to determine an approach for surgical removal.

Assessment of T1 and T2 signals can help to determine the composition of the mass.

The use of contrast, similarly as in echocardiogram, can evaluate the presence of cardiac thrombus versus a tumor.

CT Scan 

This imaging study is useful for the assessment of cardiac mass, adjacent structure and can determine the nature of the mass by evaluating the x-ray attenuation.[20]

Calcification of the mass is also visible with this imaging study, and it can also evaluate small masses.

Left Heart Catheterization with Coronary Angiogram

Left cardiac catheterization can be helpful to determine the blood supply and adjacent structures to the tumors.[21] The technique can also help determine invasion of the tumor to the epicardial vessels, and with ventriculography, one can determine the extension of the tumor into the ventricular chamber. 

Biopsy and Histological Evaluation

In vivo intracardial biopsy is a risky procedure mostly done at high volume centers with experienced surgeons.

Right-sided tumors are more likely to be biopsied to determine the histology of the tumor.[22]

Left-sided tumor biopsy has more risk for perforation and systemic embolization during the procedure.

Imaging-guided biopsy increases the success rate of a biopsy and also provides a good tissue specimen for the determination of histological origin.[23]

Cytology from the pericardial fluid can also be used to determine the underlying nature of tumors.

Ultimately, surgical resection of the tumor with histological evaluation and fluoroscopy is used to determine the type of tumor.

Treatment / Management

Primary Cardiac Tumors

Benign Tumors

Myxoma

• Surgical removal of the myxoma is necessary due to the high risk of embolization secondary to the friable structure.
• It is important to have margins free of the tumor after the resection to prevent recurrence.[24]

Lipomas

• In the absence of symptoms or arrhythmias, there is no need to intervene.

Papillary Fibroelastoma

• Left-sided papillary fibroelastomas should undergo surgical resection in patients with large mobile mass or with evidence of embolization.

Rhabdomyoma

• Most of these tumors regress spontaneously after birth, and resection rarely is necessary, except in cases of obstruction or arrhythmias.

Fibroma

• Complete surgical resection when is feasible is the recommendation.[25]

Cardiac Sarcomas

The majority of sarcomas have an overall poor prognosis; some studies have found an increase in survival rate with complete surgical resection of the sarcoma compared with patients without surgical management. Surgical removal after diagnosis is the recommendation.[26]

Secondary Cardiac Tumors

Treatment of the underlying malignancy will help with cardiac invasion, but very frequently, cardiac invasion or metastasis is a poor prognosis factor.

Management of pericardial effusion is via pericardial drainage, and if re-accumulation occurs, one can perform a pericardial window.

Differential Diagnosis

Important differential diagnoses of cardiac masses are other more common findings as thrombus or vegetations. In these situations, the clinical scenario is vital to determine the origin of the cardiac mass. 

The presence of intracardiac devices or prosthetic devices in the setting of infection increases the suspicion of vegetations.

Heart failure symptoms in patients with underlying malignancy can also be related to cardiotoxicity from chemotherapy, and this requires evaluation before determining possible metastasis or invasion of the primary tumor.

Infectious diseases can also produce intracardial and pericardial masses or effusion, and microbiological assessment is necessary.

Prognosis

The prognosis of the different cardiac tumors depends on their nature and mechanical disturbances (obstruction/insufficiency).

Primary benign cardiac tumors have the best prognosis unless multiple embolizations occur, especially when systemic because this can cause multiple strokes with different neurological involvement and physical limitations. A similar situation occurs when the tumor causes mechanical abnormalities in the conduction system, inducing arrhythmias that can be life-threatening or valvular disease-causing syncope or heart failure symptoms.[24]

Malignant tumors, especially primary tumors, are the ones with the worst overall prognosis. Survival after the first year of diagnosis is low, especially in the absence of surgical excision.[27]

Secondary cardiac tumors have a poor prognosis but mostly because the primary tumor is likely to be advanced with possible different areas of metastasis. Also, a mechanical compromise occurs in this scenario.

Complications

Complications due to cardiac tumors are mechanical.

Embolization causing strokes is a frequent complication that can present as stroke, and later while doing stroke workup, can find the cardiac mass.

Valvular disease, such as obstruction or insufficiency, is common when the mass is adjacent to the leaflets. Syncope can occur when there is a blood flow obstruction due to the mass, causing hypoperfusion to the brain and the coronaries, also predisposing to tachyarrhythmias.

The presence of masses next to the conduction system in the epicardium and myocardium can generate electrical abnormalities as atrioventricular block, complete heart block, and ventricular tachyarrhythmias.

Pericardial involvement and pericardial effusion can cause a hemodynamic disturbance with hypotension, shortness of breath, and even cardiac tamponade.

Deterrence and Patient Education

Patients with the diagnosis of cardiac masses need extensive evaluation to determine the etiology and prevent decompensation.

Cardiac masses can be abnormal tissue that can be limited to the heart tissue and after removal can prevent mechanical complications.

Enhancing Healthcare Team Outcomes

The presence of a cardiac mass requires an interprofessional approach. The differential is enormous, and the diagnosis and management need to be prompt to lower morbidity and mortality. Besides, a cardiologist, a cardiac surgeon, electrophysiologist, internist, and intensivist are essential in patient care. Cardiac nurses provide direct and monitor patients. The overall prognosis depends on the type of mass and extent of myocardial involvement.