Cardiac tumors Dr Shreetal Rajan Nair Senior Resident, Department of Cardiology, Calicut Medical College

History 1559 : Columbus , a noted pathologist – first to report 1934 : first report of a primary sarcoma of the heart diagnosed in a living patient by Barnes 1942 : surgical resection of intrapericardial teratoma by Beck 1951 : The first successful excision of a cardiac tumor performed by Maurer 1952 : Goldberg diegnosed intracavitary myxoma by angiocardiography 1968 : Shattenberg used echo to diagnose cardiac tumors

Classification secondary Breast lungs Primary benign (75%) malignant (25%) Myxoma – 50% Rhabdomyoma – 20% Fibroma Papillary fibroelastoma Lipoma Angiosarcoma Rhabdomyosarcoma Leiomyosarcoma Lymphomas

Incidence All age groups - 0.002% to 0.03% Pediatric - 0.027% to 0.08% Adults - upto 0.02% By comparison, metastatic involvement is 20 times more common

Incidence of benign tumors Shapiro LM. Cardiac tumours: diagnosis and management. Heart 2001;85:218e22. Shapiro LM. Cardiac tumours: diagnosis and management. Heart 2001; 85: 218 - 22.

LITERATURE

Tumors of the heart - Constitutional or systemic Embolic Cardiac Phenomena secondary to metastatic diseases. Specific signs and symptoms generally are determined by the location of the tumor, size, friability , mobility in the heart and depends least on the histopathology

Tumors of the heart- clinical presentations Primary tumors most commonly involve the endocardium, followed by myocardium and then epicardium Metastatic involvement of heart is reverse that of primary tumors Endocardium- obstruction to flow of blood through heart Myocardium - rhythm abnormalities Epicardium – pericardial effusion, cardiac tamponade

Approach to a cardiac tumor Differential diagnosis PUO IE/CONNECTIVE TISSUE DISEASES VALVULAR LESIONS CCF CONDUCTION ABNORMALITIES EMBOLISM SYNCOPE PERICARDIAL EFFUSION

Diagnostic evaluation Confirm the diagnosis locate the lesion within the heart Whether benign or malignant

Echocardiography Simple, noninvasive technique for initial evaluation. Images myocardium and the cardiac chambers Identify the presence of a mass and its mobility. Information about any obstruction to the circulation & whether the tumor could be a source of emboli

Echocardiography - TEE vs TTE Transthoracic echocardiography – the initial diagnostic tool Transesophageal echocardiography (TEE)- more informative. This is due to the proximity of the esophagus to the heart, the lack of intervening lung and bone, and the ability to use high-frequency imaging transducers that afford superior spatial resolution

CARDIAC MRI VS CT Both provide noninvasive, high resolution images of the heart, but MRI generally is preferred. cMRI -detailed anatomic images T1- and T2-weighted sequences help to identify the chemical microenvironment within a tumor CT -useful when calcification is present and MRI is not available or is contraindicated.

CORONARY ANGIOGRAPHY  Mapping the blood supply of tumors arising from the epicardial surfaces vital to the success of excising such tumors. Significant involvement of coronary arteries - resection and grafting of such arteries

Role of Transvenous biopsy Limited data are available on the risks and benefits considered reasonable if potential benefits outweigh risks and there is diagnostic dilemma

Benign tumors Around 75 percent of primary cardiac tumors are benign In adults, most common- myxomas (50%) Other common benign lesions- papillary fibroelastomas and lipomas. In children, the most common- rhabdomyomas and fibromas

Myxomas Most common primary cardiac neoplasm. Histology- scattered cells within a mucopolysaccharide stroma which originate from multipotent mesenchymal cells capable of neural and endothelial differentiation . Hallmark histological feature is myxoma (lepidic) cell Produce VEGF-induction of angiogenesis and the early stages of tumor growth & IL 6 -responsible for the constitutional features.

Myxoma ( lepidic ) cells

Myxomas Typically pedunculated and gelatinous in consistency; smooth, villous, or friable. Calcification , necrosis and cystic changes seen Mostly (90%) solitary About 35 % of are friable or villous, these tend to present with emboli. Larger tumors -smooth surface and associated with cardiovascular symptoms.

Myxomas The cardiovascular manifestations depend upon the anatomic location of the tumor. Mostly seen in females 40-60 years of age 80% -originate in the left atrium, most of the remainder is found in the right atrium constitutional symptoms (eg, weight loss, fever) and laboratory abnormalities

Syndrome Myxoma Characteristics Syndromic associations Younger than 40 years Biatrial ,ventricular , valves all first degree relatives should be screened Recurrent – 30% No gender predilection LAMB (lentigines, atrial myxomas,mucocutaneous myxomas, and blue nevi), NAME (nevi, atrial myxomas, myxoid neurofibroma, and ephelides Carney syndrome (atrial, cutaneous and mammary myxomas, lentigines, blue nevi, endocrine disorders and testicular tumours)

Myxoma Carney syndrome Histological features Mutations in : PRKAR1A (protein kinase A regulatory subunit 1A ) MYH8 - myosin isoform PAS Vimentin S100 and NSE - POSITIVITY

Treatment Prompt resection-due to the risk of embolization or cardiovascular complications, including sudden death Result of surgical resection is good ( <5% mortality) Cardiac autotransplantation

Papillary fibroelastomas Second most common primary cardiac tumor in adults Their appearance is compared to pom-pom or sea anemones

Clinical features Symptoms -caused by embolization of the tumor/thrombus. most common clinical presentation- stroke /TIA. Commonly attached to the aortic valve 30%- incidentally diagnosed by echocardiography, at cardiac surgery, or at autopsy

TREATMENT SURGERY – 1. patients who have had embolic events or complications directly related to tumor mobility (eg, coronary ostial occlusion) 2.Those with highly mobile or large (≥1 cm) tumors Recurrence not reported

Lipomas Lipomas &fibrolipomas - characterized by a predominance of benign fatty cells. About half of these tumors occur in the subendocardial region.Others in the myocardial and subepicardial regions They may also occur on valves

Lipoma

Lipomas Symptoms- generally related to local tissue encroachment (arrhythmias, conduction block, sudden death) valvular tumors – insufficiency & symptoms of heart failure Diagnosis - echocardiography and the distinctive fat pattern on MRI. Require resection.

Lipomatous hypertrophy of the interatrial septum Exaggerated growth of normal fat existing within the septum and is not a true tumor. Developmental disorder caused by expansion of adipose tissue trapped in the interatrial septum during embryogenesis The septal hypertrophy may be as much as 2 cm in thickness and is seen primarily in older patients and in those who are obese

Lipomatous hypertrophy of the interatrial septum Associated with the presence of CAD in proportion to the degree of atrial septal thickness Indistinguishable from lipoma except that the former occurs in the atrial septum with a typical distribution (generally sparing the fossa ovalis). In the absence of symptoms of atrial arrhythmias, heart block or rare vena caval obstruction, they do not require resection

Pericardial lipomas Incidental finding and clinically insignificant. Rarely assumes gigantic proportions and its appearance on a chest radiograph may be mistaken for a huge pericardial effusion or massive cardiomegaly Benign pericardial lipomas can infiltrate the myocardium. If the ventricular septum is invaded, communication between the pericardial space and the right ventricular cavity may result.

Rhabdomyomas Develop almost exclusively in children, mostly <1 year of age 80 to 90% are associated with tuberous sclerosis Usually found in the ventricular walls/AV valves. Most regress spontaneously Resection is usually not required unless symptomatic Symptoms –due to obstruction of blood flow through the heart or consist of rhythm disturbances Present with features of preexcitation on the ECG

Rhabdomyositis A rare form of cardiomyopathy in infants Tumor nodules are not grossly apparent Microscopically, the cardiac muscle fibers and conduction system are diffusely involved with rhabdomyomatous histologic changes Recurrent atrial tachycardia and sudden death from intractable ventricular tachycardia

Why rhabdomyomas regress? High expression of ubiquitin which starts expressing from 32 week onwards Absent mitotic activity Ubiquitin is responsible for the degradation of rhabdomyoma cells and hence tumor regression Characteristic spider cells are formed in the process.

Spider cells in rhabdomyoma

Fibromas  Second most common pediatric cardiac tumor and can also occur in adults Histologically similar to fibromas arising elsewhere in the body. Usually arise in the ventricular muscle and may become quite large. Do not regress spontaneously. Arise approximately 5 times more frequently in the LV than RV

Fibromas Most common symptom, due to obstruction of blood flow or interference with valvular function. Myocardial dysfunction and conduction disturbances Echocardiography, supplemented with CT/MRI confirms the diagnosis. Symptomatic tumors should be resected. Complete resection of very large tumors may require cardiac transplantation.

Fibromas

Teratomas Arise within the pericardium, but do not originate from cardiac structures Although generally benign,can have serious mechanical consequences by causing tamponade or through direct pressure on the heart. Risk of death in-utero or immediately after birth

Teratomas Treatment therefore requires either fetal tumor excision, or caesarean section and immediate operation on the newborn Have a single blood supply and are not invasive, properly timed tumor surgery is straightforward and successful

Purkinje cell tumors/hamartomas Consist of small, flat sheets of cells most frequently located in the left ventricle, and on the endocardial and epicardial surfaces Undetectable by echocardiographic or radiologic techniques. Tumors of young children and present with incessant ventricular tachycardia ECGs often demonstrate a bundle branch pattern (right bundle branch block when the tumor is in the left ventricle). Electrophysiologic studies can localize the tumors, facilitating surgical excision.

Paragangliomas Neuroendocrine tumors that can be hormonally active or inactive. In tumors not producing catecholamines, symptoms are due to cardiac compression or tamponade. In contrast, cardiac paragangliomas that are hormonally active primarily produce norepinephrine and may cause systemic symptoms (eg, headache, sweating, tachycardia, hypertension) Hormonally inactive tumors are more frequent in the pericardium

Paragangliomas May be localized with echocardiography. Extremely vascular Coronary angiography -to plan the operative resection

Paragangliomas Paragangliomas (benign/malignant) within the pericardium parasitize the cardiac blood supply and hence are very difficult to excise All intrapericardial paragangliomas require resection Cardiopulmonary bypass and even circulatory arrest may be required due to the high degree of vascularity, or to moderate the extreme hypertension possible from tumor manipulation or hormonally active tumors If complete resection is not possible, cardiac transplantation may be required

PRIMARY MALIGNANT TUMORS Malignant tumors constitute approx 15% of primary cardiac tumors Sarcomas are the most common Virtually all types of sarcomas have been reported in the heart Prognosis depends on Mitotic activity, extent of tumor necrosis and cellular differentiation.

Malignant cardiac tumors Clinical presentation is largely determined by the location of the tumor, rather than its histopathology. The diagnostic approach relies upon echocardiography, MRI, and CT to define the presence of a tumor and its anatomic relationship to normal structures Increased mitoses

Angiosarcomas Composed of malignant cells that form vascular channels. Pathology may overlap with Kaposi's sarcoma, which can also involve the myocardium Arise predominantly in the right atrium

Rhabdomyosarcomas Constitute as many as 20% of all primary cardiac sarcomas Most commonly found in adults, although they have also been described in children. Multiple sites of myocardial involvement are common, No predominant localization within any area of the heart.

Fibrosarcomas Fibrosarcomas and malignant fibrous histiocytomas are white fleshy ("fish flesh") tumors that are composed of spindle cells, and may have extensive areas of necrosis and hemorrhage These tumors tend to extensively infiltrate the myocardium

Leimyosarcomas Spindle-celled, high-grade tumors that arise more frequently in the left atrium These sarcomas have both a high rate of local recurrence and systemic spread.

Mesothelioma  Although most arise in the pleura, these can also arise from the pericardium, where they are usually malignant Those arising in the pericardium produce tamponade and constriction Seen with echocardiography, CT scan, MRI and sometimes by chest x-ray Pericardiocentesis may yield a cytologic diagnosis

  Mesothelioma More rarely they may arise as benign tumors of the AV node where they may produce heart block Can be confirmed with echocardiography Resection is the treatment of choice for mesothelioma, but the prognosis with malignant pericardial mesotheliomas is very poor The addition of radiation and/or chemotherapy has been attempted but has not been shown to be of value.

Treatment and prognosis In general, sarcomas proliferate rapidly, and cause death through widespread infiltration of the myocardium, obstruction of blood flow through the heart, and/or distant metastases. Although complete resection is the treatment of choice, most patients develop recurrent disease and die of their malignancy even if their tumor can be completely resected.

Treatment and prognosis The median survival is typically 6 to 12 months although long-term survival has been reported with complete resection. Low-grade sarcomas may have a better prognosis Adjuvant chemotherapy and radiation therapy have been used infrequently either after resection to improve results or in metastatic involvement. Rhabdomyosarcomas may have a better outcome with chemotherapy

Treatment and prognosis The poor results with surgical resection have led to occasional attempts to treat patients with cardiac transplantation, if extracardiac disease is not present cardiac autotransplantation is another novel approach. Here, the heart is excised, tumor resected ex vivo, and the heart is reconstructed before being reimplanted. The advantage of this procedure is the increased ease with which major resection and reconstruction can be performed, while at the same time avoiding the need for antirejection treatment

Lymphomas and other tumors Primary lymphomas arising in the myocardium have been reported. In a review of 40 cases identified from the literature between 1995 and 2002, the outlook was generally poor However, 38 percent of cases achieved a complete response with systemic therapy. Other tumors may also arise in the heart, including paragangliomas and extramedullary plasmacytomas

SECONDARY CARDIAC TUMORS Cardiac involvement may arise from hematogenous metastases, direct invasion from the mediastinum, or tumor growth into the vena cava and extension into the right atrium Malignant melanomas are particularly likely to metastasize to the heart. Other solid tumors commonly associated with cardiac involvement include lung cancer, breast cancer, soft tissue sarcomas, renal carcinoma, esophageal cancer, hepatocellular carcinoma, and thyroid cancer. There is also a high prevalence of secondary cardiac involvement with leukemia and lymphoma

Secondary cardiac tumors Cardiac or pericardial metastasis should be considered whenever a patient with known malignancy develops cardiovascular symptoms, particularly if this occurs in conjunction with cardiomegaly, a new or changing heart murmur, electrocardiographic conduction delay, or arrhythmia. Emboli thought to originate in the heart should also raise the possibility of cardiac involvement with tumor. Cardiac metastases rarely may be the first manifestation of malignant disease

Secondary cardiac tumors The specific symptoms reflect the site of cardiac involvement. The diagnostic evaluation is the same as that for primary cardiac tumors and relies upon echocardiography, MRI, and CT. Resection of cardiac metastases has been used to provide symptom palliation and prolong life

Summary Cardiac tumours are rare. A cardiac mass most likely represents a thrombus or vegetation. Most cardiac tumours are secondary, ie, originate from a primary tumour elsewhere. Most primary cardiac tumours are benign In addition to history, a non- invasive diagnosis of cardiac tumours can usually be made by the following: -Histology based likelihood. -Tumour location. -Age at presentation. -Imaging characteristics

Benign tumors of the heart

Malignant tumors of the heart

Imaging features of cardiac features – in a nut shell

Summary Rhabdomyomas usually decrease in size with age. The most common cardiac tumour involving valves is a papillary fibroelastoma. The most common primary malignant tumour is a sarcoma. Angiosarcomas are the most common histologic subtype of sarcoma and are usually found in the right atrium The most common benign cardiac tumour is a myxoma. Myxomas are generally found in the left atrium arising from a stalk attached to the fossa ovalis membrane. The most common primary cardiac tumours in children are rhabdomyomas and fibromas, both of which are benign.

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