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Cardiac Myxoma

Cardiac myxoma is the most common of the primary tumors of the adult heart, all of which are very rare. Cardiac myxoma is a benign Benign Fibroadenoma neoplasm that arises from primitive multipotent mesenchymal cells. Most occur sporadically, but some are a part of some familial syndromes. All 4 chambers may give rise to myxoma, but 90% originate and grow in the atria, with a left-to-right ratio of approximately 4:1. Diagnosis is made by echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA), cardiac magnetic resonance Cardiac magnetic resonance Aortic Regurgitation imaging (MRI), or cardiac computed tomography (CT). Complete surgical excision is required because of the substantial risk of embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding and cardiovascular complications, including sudden death.

Last updated: Nov 10, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Cardiac myxoma is a benign Benign Fibroadenoma primary tumor Tumor Inflammation of the heart.

Epidemiology

  • Primary cardiac tumors are very rare: incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency < 0.1%
  • Myxoma is the most common primary cardiac tumor Tumor Inflammation.
  • Most common in adults, but can happen in all age groups
  • 90% of cardiac myxomas arise in the atria, with left-to-right ratio of 4:1.
  • Women > men
  • Most are sporadic Sporadic Selective IgA Deficiency.
  • Most common inherited form is a part of Carney complex:
    • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder:
      • Atrial and extracardiac myxomas
      • Schwannomas
      • Pigmentation abnormalities
      • Endocrine and other tumors 
    • Not the same as Carney triad Carney Triad Pheochromocytoma or Carney-Stratakis syndrome

Etiology

  • Arises from primitive multipotent mesenchymal cells 
  • No consistent genetic alterations in sporadic Sporadic Selective IgA Deficiency myxomas
  • Growth factors may contribute to tumor Tumor Inflammation formation, e.g., vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing (VEGF), an angiogenic factor.
  • Familial syndromes with myxomas are associated with specific genetic defects:
    • Carney complex: null mutations in PRKAR1A PRKAR1A Schwannoma, encoding a regulatory subunit of a cyclic-AMP–dependent protein kinase Protein kinase A family of enzymes that catalyze the conversion of ATP and a protein to adp and a phosphoprotein. Interferons
    • Mazabraud’s syndrome: single or multiple intramuscular myxomas with fibrous Fibrous Fibrocystic Change dysplasia; activate mutations in the GNAS1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics

Pathophysiology

Anatomy and histology

  • 80% originate in the left atrium (most commonly, fossa ovalis Fossa ovalis Prenatal and Postnatal Physiology of the Neonate).
  • Most others are in the right atrium.
  • Range from 1–15 cm in diameter
  • Typically pedunculated tumors with gelationous consistency Consistency Dermatologic Examination
  • Microscopic features:
    • Scattered stellate or globular cells in the mucopolysaccharide stroma
    • Can be accompanied by hemorrhage and chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Small tumors tend to be villous and friable.
    • Larger tumors usually have a smooth surface.
Myxoma

Surgical gross pathology specimens (A, B, C, D, E) and histologic (F) findings of bilateral atrial myxomas
A: myxoma from left atrium
B: myxoma from right atrium
C: embolic myxoma from aortic bifurcation
D: embolic myxoma from left popliteal artery
E: embolic myxoma from right popliteal artery
F: histologic findings of myxoma (H&E (hematoxylin and eosin) x400): characteristic stellate tumor cells within an abundant myxoid stroma

Image: “Myxoma” by Division of Cardiology, Department of Internal Medicine, College of Medicine, Hanyang University, Seungdong-Gu, Heangdang-Dong 17, 133-070 Seoul, South Korea. License: CC BY 4.0

Pathophysiologic mechanisms

  • Obstruction of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure: causes heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Interference with cardiac valves:
  • Embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding:
    • More common with small tumors (from fragments or surface thrombi)
    • More commonly systemic than pulmonic
  • Direct invasion of the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy:
    • Left ventricular dysfunction
    • Arrhythmias/heart block
    • Pericardial effusion Pericardial effusion Fluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
  • Invasion of the adjacent lung (can mimic lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer)
  • Cytokine production (e.g., interleukin-6 Interleukin-6 A cytokine that stimulates the growth and differentiation of B-lymphocytes and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-lymphocytes; monocytes; and fibroblasts. Interleukins)

Clinical Presentation

Left-side myxomas (approximately 85%)

  • Symptoms similar to mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) or regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) (left heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)):
    • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
    • Orthopnea Orthopnea Pulmonary Edema
    • Paroxysmal nocturnal dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
    • Cough/ hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis
    • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Neurologic symptoms: secondary to systemic emboli
  • Arrhythmias

Right-side myxomas (approximately 15%)

  • Symptoms of tricuspid disease (right heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)):
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • Peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Hepatomegaly
    • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
    • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
    • Sudden death
  • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism
  • If patent foramen ovale Foramen ovale An opening in the wall between the right and the left upper chambers (heart atria) of a fetal heart. Oval foramen normally closes soon after birth; when it fails to close the condition is called patent oval foramen. Patent Foramen Ovale is present:

Constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

  • May be seen in 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 
  • Cytokine release:
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia

Diagnosis and Management

Physical examination

  • Left atrial tumors:
    • Diastolic “ tumor Tumor Inflammation plop” on auscultation
    • Pulmonary edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema: rales Rales Respiratory Syncytial Virus or crackles on auscultation
  • Right atrial tumors:
    • Diastolic murmur
    • Jugular venous distention
    • Generalized edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Hepatomegaly
    • Abdominal ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites

Imaging

  • Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) (usually 1st imaging technique):
    • Transesophageal echocardiography Transesophageal echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues using a transducer placed in the esophagus. Imaging of the Heart and Great Vessels ( TEE TEE Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues using a transducer placed in the esophagus. Imaging of the Heart and Great Vessels) gives better resolution.
    • Can usually identify:
      • Mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
      • Mobility
      • Obstruction
      • Embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding 
  • Cardiac magnetic resonance Cardiac magnetic resonance Aortic Regurgitation imaging ( CMR CMR Imaging of the Heart and Great Vessels): detailed anatomic imaging
  • Cardiac computed tomography (CCT): if CMR CMR Imaging of the Heart and Great Vessels not available
  • Positron emission tomography ( PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging) scan helps differentiate:
    • Metastatic tumors versus atrial myxoma 
    • Lipomatous septal hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation versus atrial myxoma
  • Coronary angiography Coronary angiography Radiography of the vascular system of the heart muscle after injection of a contrast medium. Myocardial Infarction:
    • “Sea anemone” appearance on angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery
    • Mapping of blood supply: may be needed for surgical planning

Transvenous biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

  • Risk of embolism
  • Should only be performed if diagnosis is uncertain and benefits outweigh the risks

Management

  • Surgical resection is required because of:
    • Risk of embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding
    • Cardiovascular complications
    • Risk of sudden death
  • Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:
    • Operative mortality Mortality All deaths reported in a given population. Measures of Health Status rate < 5%
    • Recurrence: 2%–5% of cases, more common if familial or multiple
    • Cardiac autotransplantation (with atrial reconstruction) or transplantation may be necessary for recurrent atrial myxoma.
    • Atrial arrhythmias or atrioventricular conduction abnormalities in 26%
Gross pathology of excised left atrial myxoma

Gross pathology of excised left atrial myxoma, measuring 7 × 6 × 4 cm: Note the translucency of the tumor, due to its abundant content of acid mucopolysaccharide ground substance.

Image: “Gross pathology” by Department of Neurology, Hospital of International University of Health and Welfare, 537-3 Iguchi, Nasushiobara, Tochigi 329-2763, Japan. License: CC BY 3.0

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Differential Diagnosis

Benign Benign Fibroadenoma primary cardiac tumors or tumor-like masses

  • Intracardiac Intracardiac Total Anomalous Pulmonary Venous Return (TAPVR) thrombus: the most common type of intracardiac Intracardiac Total Anomalous Pulmonary Venous Return (TAPVR) mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in adults. May occur following myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction with ventricular thrombus formation, or with atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation and mitral stenosis Mitral stenosis Mitral stenosis (MS) is the narrowing of the mitral valve (MV) orifice, leading to obstructed blood flow from the left atrium (LA) to the left ventricle (LV). Mitral stenosis is most commonly due to rheumatic heart disease. Mitral stenosis leads to impaired LV diastolic filling, increased LA pressure, and LA dilation. Mitral Stenosis where atrial thrombi predominate. Left-sided thrombi are a common source of stroke and other arterial embolic syndromes. Ultrasound and CMR CMR Imaging of the Heart and Great Vessels aid in the diagnosis. Treatment is usually with anticoagulation Anticoagulation Pulmonary Hypertension Drugs.
  • Rhabdomyoma: the most common pediatric cardiac tumor Tumor Inflammation; a benign Benign Fibroadenoma neoplasm of muscle cells, often multiple, associated with tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor. Frequently undergoes spontaneous regression Regression Corneal Abrasions, Erosion, and Ulcers; diagnosis is made by clinical impression and imaging.
  • Fibromas: 2nd most common primary pediatric cardiac tumor Tumor Inflammation. Composed of fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis, which usually arise in ventricular septum. Fibromas may be part of Gorlin syndrome Gorlin Syndrome Basal Cell Carcinoma (BCC) (nevoid basal cell carcinoma Basal cell carcinoma Basal cell carcinoma is the most common skin malignancy. This cancer arises from the basal layer of the epidermis. The lesions most commonly appear on the face as pearly nodules, often with telangiectatic blood vessels and ulceration in elderly individuals. Basal Cell Carcinoma (BCC) syndrome); does not regress, but may not need treatment if small.
  • Lipomas: rare encapsulated Encapsulated Klebsiella neoplasm of mature fat cells. May originate from subendocardium Subendocardium Heart: Anatomy, subpericardium, or from the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy. Lipomas are more frequent in the left ventricle or right atrium.
  • Papillary fibroelastoma: the 2nd most common primary cardiac tumor Tumor Inflammation in adults. Papillary fibroelastoma are small sea anemone–shaped endocardial tumors with frond-like structures, usually on mitral or aortic valves, where they can cause symptoms due to embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding, either of the tumor Tumor Inflammation itself or thrombus. Imaging is diagnostic, and surgery is recommended.

Malignant tumors of the heart

  • Sarcoma: malignant tumor Tumor Inflammation originating from the connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology cells. Exceedingly rare in the heart. Angiosarcoma is the most common type.  Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is poor, as these tumors tend to grow rapidly and recur even when completely resected.
  • Metastatic tumors: 20 times more common than primary tumors. May be present in 20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship dying of cancer. Symptoms depend on the site of cardiac involvement. Diagnosis is made with echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA), CMR CMR Imaging of the Heart and Great Vessels, or CCT.

References

  1. Valvular Heart Disease. (2020). In Kumar, V., Abbas, A. K., Aster, J.C., (Eds.). Robbins & Cotran Pathologic Basis of Disease. (10th ed., p. 579).
  2. Gaasch, W.H., Salm, T.J.V. (2020). Cardiac tumors. UpToDate. Retrieved December 17, 2020, from https://www.uptodate.com/contents/cardiac-tumors?search=Atrial%20myxoma&source=search_result&selectedTitle=1~46&usage_type=default&display_rank=1#H12461347
  3. Kuon, E., Kreplin, M., Weiss, W., Dahm, J.B. (2004). The challenge presented by right atrial myxoma. Herz. 2004 Nov;29(7):702-9. doi: 10.1007/s00059-004-2571-7. PMID: 15580325.

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