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 Table of Contents  
Year : 2023  |  Volume : 7  |  Issue : 1  |  Page : 8-15

Clinicopathological Correlation of Cardiac Myxoma- Insights from a Large Volume Tertiary Cardiac Center in South India

1 Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
2 Department of Pathology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India

Date of Submission30-Aug-2022
Date of Decision06-Oct-2022
Date of Acceptance07-Oct-2022
Date of Web Publication23-Jan-2023

Correspondence Address:
Dr. Sriranga Rangashamaiah
Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_42_22

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Background: Cardiac myxomas are the most common benign primary cardiac tumors. They present with a variety of nonspecific cardiac and noncardiac symptoms. Six decades into the first description of the tumor, the explanation of noncardiac symptoms remains an enigma. Literature is sparse to look into the histopathological correlation of the symptoms. Materials and Methods: A prospective study of 47 myxoma patients operated on in our center between August 2016 and December 2018 wherein, their demographic data, electrocardiogram (ECG), echocardiography data, hematological and radiological parameters, and histopathological features were analyzed. Results: Among 47 myxoma patients, 27 were female and 20 were male patients, with an average age of presentation being 48.55 ± 14.01 years for females and 43.81 ± 12.98 for males, P = 0.006. Dyspnea was the most common presenting symptom, seen in 37 (78.4%) patients. Tumor plop was more common among patients with embolization. Ninety-four percent of the myxomas were mobile and solitary, causing significant mitral valve obstruction in 69% of cases and mitral valve regurgitation in 79% of patients. Pulmonary artery hypertension because of myxomas was found in 38% of the patients. The left atrial enlargement was the most common ECG abnormality and was found in 13 (27.7%) patients. Elevated serum C-reactive protein was associated with palpitation whereas neutrophilic infiltration of the tumor was associated with chest pain. Three of the patients recruited were recurrent cases. Infective endocarditis was seen in one patient. Conclusion: Echocardiography gives significant information about the tumors, including the site, mobility, morphology, numbers, and the correlation of symptoms which are due to hemodynamic disturbances caused by the tumor. All the myxomas in our study were solitary in nature and most of them were attached to left interatrial septum at the level of fossa ovalis.

Keywords: Benign cardiac tumor, cardiac myxoma, clinical and morphology correlation

How to cite this article:
Jagadeesh H V, Rangan K, Rangashamaiah S, Ramegowda KS, Nanjappa MC. Clinicopathological Correlation of Cardiac Myxoma- Insights from a Large Volume Tertiary Cardiac Center in South India. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:8-15

How to cite this URL:
Jagadeesh H V, Rangan K, Rangashamaiah S, Ramegowda KS, Nanjappa MC. Clinicopathological Correlation of Cardiac Myxoma- Insights from a Large Volume Tertiary Cardiac Center in South India. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 May 29];7:8-15. Available from: https://jiaecho.org/text.asp?2023/7/1/8/368418

  Introduction Top

Heart tumors are one of the rarest cardiac diseases. They are divided into primary (those which arise from the heart) and secondary (which metastasis into the heart). The primary cardiac tumors can in turn be benign or malignant. The incidence rates vary among many studies. In the autopsy series, secondary tumors are more common ranging from 1.5% to 21%, whereas primary cardiac tumors constitute 0.001%–0.28%.[1],[2],[3] The most common primary benign cardiac tumors are cardiac myxoma constituting 50% of the primary cardiac tumors. Cardiac myxoma was first described by Goldberg in 1952.[4] Although it has been six decades into the description of the tumor in the literature, many of its features remain an enigma and controversial. Cardiac myxomas present with a myriad of symptoms, which include cardiac (explained by mechanical factors) as well as noncardiac (cannot be explained by mechanical factors alone). The cardiac symptoms of myxoma depend on the site, size, and location of the tumor. However, noncardiac symptoms such as fever are often not explained. The present study was conducted to find the clinical, hematological, radiological, and pathological association of cardiac myxomas.

  Materials and Methods Top


This was a prospective observational study done at Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, between August 2016 and December 2018 [Figure 1]. The center is one of the largest tertiary care centers for the management of cardiovascular diseases in South East Asia, and acts as a referral center for the most parts of Karnataka state and adjoining parts of neighboring states in South India. Our center provides cardiovascular care for a mainly lower and middle socioeconomic class population with adult and pediatric cardiology, adult and pediatric cardiac surgery, electrophysiology, and vascular surgery departments catering to nearly 378,000 outpatients and 36,000 inpatients every year. Close to 2100 catheterization procedures and 260 surgical procedures are conducted every month.
Figure 1: Skeleton diagram of the study design

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For this study, patients aged >18 years with clinical and echocardiographic diagnosis of intracardiac tumor and admitted for surgical excision of the tumor were included. Intraoperative tumor characteristics were noted and the excised surgical specimens were examined and reported by the pathologist. The secondary cardiac tumors, intracardiac thrombus, and those patients with no consent for the study were excluded. Data of patients with histopathological diagnosis of cardiac myxoma were collected. Demographic characteristics such as age and gender and clinical parameters including symptoms and examination findings such as heart sounds, tumor flop, and associated murmurs were noted. Laboratory parameters such as complete blood count, erythrocyte sedimentation rate (ESR), electrocardiogram (ECG) findings such as axis, chamber enlargement, and chest X-ray findings such as cardiomegaly, chamber enlargement were recorded. All patients had already undergone a detailed two-dimensional echocardiogram for the assessment of tumor location, size, mobility, associated valvular lesions, left ventricular (LV) systolic function and the presence of pericardial effusion. These findings were noted. The LV ejection fraction was considered reduced if <52% for men and <54% for women.[5] Based on the location of the tumor, they were classified into typical location – attachment to the left side of interatrial septum (IAS) or atypical location – attachment other than the left side of IAS. Mitral inflow obstruction was defined as the mean gradient of more than 5 mmHg across mitral valve due to obstruction of flow by the tumor in the absence of valvular mitral stenosis.[6]

On gross examination, the following points were recorded:

  • Sessile/pedunculated, globular/lobulated/polypoid, smooth/with papillary projections, the color of the tumor- pale gray/pearly white/red hemorrhagic, consistency and calcification, cystic change, and the appearance of the cut surface

Representative tissue bits were processed and embedded in paraffin blocks. Five μ thick sections were cut and stained with hematoxylin and eosin stain. Sections from the glandular variant were additionally stained with Alcian Blue, periodic acid–Schiff, and immunohistochemistry markers namely cytokeratin and vimentin. On microscopic examination, the following findings were noted:

Myxoma cells (elongated/stellate/fusiform) arranged singly/in cords/vasoformative rings with oval/round/elongated nuclei and presence of mitosis. The stroma was observed for the presence of vessels (thin-walled cavernous/thick-walled), hemorrhage (recent/old), hemosiderin deposition, calcification, Gamna–Gandy bodies, and metaplastic bone formation. The presence of inflammatory cells – neutrophils/lymphomononuclear cells were noted. The sections were also carefully screened for the heterologous components.

Statistical analysis

The analysis was done using IBM- SPSS (Statistical Package for the Social Sciences) version 26 software, New York , USA. The metric variables such as age and tumor size were using an independent t-test. If standard deviation was more than half the value of the variable, Mann–Whitney test was used to find the P values. For proportions, Chi-square/Fischer's exact t-test was used as appropriate.

  Results Top

Our study group included 47 sporadic cases, 27 (57.45%) were females and 20 (42.55%) were males, with females being a decade younger than their male counterparts (43 years vs. 55 years) as summarized in [Table 1].
Table 1: Demographics, clinical features, blood investigations, electrocardiogram, and chest X-ray findings*

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The most common symptom in myxoma was dyspnea seen in 78% of patients followed by cough, paroxysmal nocturnal dyspnea (PND), and chest pain seen in 34%, 28%, and 26%, respectively. Embolism symptoms were seen in 11% of patients. Constitutional symptoms such as fever and joint pain were seen in 28% and 15% of patients. Six percent of patients had incidentally detected asymptomatic myxomas. The complications such as cardiovascular accidents were seen in 11% of patients [Table 1].

Most commonly, it was located at the left side of IAS (87%). On clinical examination, loud S1 was found in 70% followed by middiastolic murmur, loud P2, tumor plop, and pansystolic murmur in 64%, 43%, 24%, and 17% of patients, respectively.

Among the blood investigations, elevated ESR was found in 60% of patients, followed by leukocytosis and eosinophilia in 28% and 11% of patients. Chest X-ray findings suggestive of cardiomegaly were found in 43% of patients, left atrial enlargement was seen in 38% of the patients followed by left heart border straightening in 32% of cases.

Echocardiography revealed that 94% of the myxomas were mobile in nature, 87% were present at the typical location and about 68% of them were causing mechanical obstruction across the mitral valve [Table 2]. Six percent of the patients had pericardial effusion and 38% of them had pulmonary arterial hypertension.
Table 2: Echocardiography and pathological characteristics

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[Table 3] summarizes clinical presentation according to the tumor size, location and the gross pathology. Gross pathology and histopathological findings are further described in [Table 4]. These are also discussed subsequently. The [Table 5] summarizes the operative details.
Table 3: Clinical and tumor characteristics

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Table 4: Pathological characteristics

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Table 5: Operative and postoperative details

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  Discussion Top

The study center is one of the largest tertiary cardiac centers in South Asia catering to the majority of the South Indian states. The epidemiological description of myxoma is classically divided into familial and sporadic forms. Familial is autosomal dominant with variable penetrance and is common among males. In our study, female-to-male ratio was 1.3:1 which is concurrent with other studies.[7] The female predilection of the tumor has been postulated to be the effect of estrogen and progesterone receptor expressions in cardiac myxomas.[8] The common age of presentation of myxoma is between the third and sixth decades of life. In our study, the females presented at a lower mean age (within the reproductive age group) of 43.81 ± 12.98 years as compared to males at 54.95 ± 13.04 years (P = 0.006). The younger age of presentation among females may be the result of the hormone expression status of myxomas.

The clinical features in myxoma are variable and may be intermittent based on its site, size, and mobility as summarized in [Table 3]. In our study, 44 (93.6%) patients diagnosed with myxoma had at least 1 of the 3 cardinal symptoms such as cardiac, embolic, and systemic symptoms. There are no population-based studies on the incidence of symptoms in patients with cardiac myxoma. Among the hospital-based studies, asymptomatic patients were 5.5% in the latter part of the 20th century.[9] Even with the increased utility of imaging modalities in the current era, in our study, there was no significant increase in the detection of asymptomatic cardiac myxomas. This is biased probably because our study center caters to primarily lower socio-economic groups who would seek medical attention only when they are symptomatic.

Hemodynamic consequences of myxomas may lead to left-sided symptoms (dyspnea, PND, orthopnea, and cough) or right-sided symptoms (pedal edema). Among cardiac symptoms, dyspnea was the most commonly found symptoms (in 78.4% of the patients) which is consistent with the available literature. The presence of a tumor in the left atrium was more associated with dyspnea as compared to the right atrium (78.7% vs. 42.9%, P = 0.029). This is due to the obstructive nature of the tumor around the mitral valve which causes pulmonary venous congestion and dyspnea; however, there was no gender, age, or size-based predilection for dyspnea.

Syncope/dizziness was more common among males 7 (35%) versus females 2 (7.4%), P = 0.026. It was also more common among patients with atypical location of the tumor (apart from IAS, 66.7% patients) as compared to those with the typical location (12.2% patients). This is probably because of the obstruction to right ventricular/LV filling in tumors with the atypical location.

Embolic symptoms represent one of the very serious clinical consequences of myxoma. Stroke was the only embolic symptom noticed in our study (5 patients). Embolism in myxoma has been attributed to tumor fragmentation or migration of the tumor to the peripheral circulation. The size of the tumor did not have any significant effect on embolization. The mean tumor area among nonembolized tumors was 12.2 ± 6.1 mm2 as compared to embolized ones (area 11.9 ± 6.2 mm2, P = 0.914). There have been scientific studies showing a positive association of the type of tumor on gross pathology correlating with embolization. Papillary tumors are more associated with embolization. In our study, among five embolized patients, 4 of them had a papillary variety of tumor and one patient had a solid tumor. However, the sample size is very small to prove statistical significance.

The unique presentation of myxomas is that despite being tumors, they exhibit connective tissue disorder-like constitutional symptoms. It was seen in 13 (27.7%) patients without any gender difference. This presentation is because of the secretion of interleukin 6 (IL 6) and 8. IL 6 has pleiotropic effects which lead to increased B-cell production and polyclonal immunoglobulin synthesis responsible for connective tissue symptoms.[10]

High C-reactive protein (CRP) was found more commonly in patients with palpitations (76.9%) as compared to those without palpitations (41.2%). It is possible that the patients with high CRP had more episodes of paroxysmal atrial fibrillation (AF) in the presence of myxoma causing palpitations.[11]

Clinical examination

Loud S1 was found in 29 (78.4%) of the patients with dyspnea as against 4 (40.0%) without dyspnea, P = 0.019. Loud S1 correlates with obstruction; hence, dyspnea was present due to obstruction to blood flow through the mitral valve causing pulmonary congestion symptoms. Tumor plop correlated with embolism; it was noticed that among five patients with embolism, 3 (60%) had tumor plop versus 8 (19.0%) among those without embolism, P = 0.041. Tumor plop represents mobile tumor prolapsing across the mitral valve; hence, chances of thrombi fragmentation and dislodgment could be more causing embolization.[12]

Electrocardiogram abnormalities

More than half of our patients (60%) had abnormal ECG findings. Axis deviation was a more common finding seen in 36% of the cases (left-axis deviation in 11 patients, right-axis deviation in 5 patients) followed by left atrial enlargement (27.7%). Left anterior hemiblock is the most common cause of left-axis deviation in the normal population and hence it was the most common abnormality found in ECG of the myxoma patients also. AF or atrial flutter (8.5%) or conduction disturbances (15%) were less common. However, compared to the general population with an AF prevalence of 0.95%, AF was much more common in myxoma patients, probably because of tumors irritating the atria and triggering AF.[13]

Chest X-rays

Chest X-rays were abnormal in 22 (42.6%) patients. Cardiomegaly was the most common chest X-ray abnormality seen in 20 (42%) followed by left atrial enlargement in 18 (38%) and straightening of the left heart border in 31% of the cases. Pericardial effusion was present in only one patient. These findings were similar to other studies except that in our study one patient presented with pericardial effusion.[14]

Echocardiography findings

Echocardiography findings are summarized in the [Table 2]. All patients had solitary myxomas. Multiple myxomas are usually found in Carney's complex.[15] Eighty-five percent of the myxomas in our study were found in the typical location of left side of the IAS at the fossa ovalis as found in other studies [Figure 2].[16] Ninety-four percent of them were mobile and 68% caused significant mitral valve obstruction due to the mechanical factor. Pulmonary arterial hypertension was found in 38% of the cases. No correlation was found between the size of the myxomas and symptoms, but chest pain and dyspnea were commonly seen with tumor size of >5 cm, but it was not statistically significant (P = 0.067; P = 0.07, respectively) [Table 3].
Figure 2: Echocardiography showing myxoma causing valve damage and mitral regurgitation. 2D: Two-dimensional, LA: Left atrial

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Pathology findings

Based on gross pathology findings, Suttons' classification of myxoma has two distinct forms: solid and papillary [Figure 3].[17] The cystic form is very rare and limited to the case reports.[18] Solid myxomas were the most common in our study also (25 cases, 53.1%) [Table 4]. Papillary myxomas, which are brittle and irregular in shaper, were the second most common type (21 cases, 44.7%). These papillary myxomas have an unusual secretory activity that releases metalloproteinase and the enzymes which degrade the extracellular matrix and hence cause tissue fragmentation and embolism.[19] Solid myxomas presented with more constitutional symptoms, which were present in 10 (40%) of solid tumors as compared to 3 (14.2%) in papillary tumors, P = 0.046. This association is novel and the reason for the same has not been explained. However, it could be due to more production of IL-6 by solid tumors as compared to the papillary variety. There was no correlation between gross pathology and clinical symptoms such as joint pain, weight loss, appetite, chest pain, and loss of appetite.
Figure 3: (a) Gross pathology showing encapsulated solid tumor. (b) Gross pathology showing papillary variety of myxoma

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Histopathology and symptoms

Myxoma is a neoplasm composed of stellate to plump cytologically bland mesenchymal cells set in a myxoid stroma [Figure 4].[20] The tumors were examined for neutrophilic, lymphocytic, and eosinophilic infiltration, presence of calcification, and fibrosis as summarized in [Table 4]. These findings were correlated with constitutional symptoms, joint pain, weight loss, appetite, chest pain, and loss of appetite. A positive association was found between neutrophilic infiltration of the tumor and the presence of chest pain. Eleven patients had neutrophilic infiltration, out of which 3 (27.3%) were without chest pain and 8 (72.7%) had chest pain, P ≤ 0.001.[21]
Figure 4: Histopathology of myxoma

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Recurrent myxomas

The overall risk of recurrence is about 12% and 22% for familial and complex myxomas, respectively, whereas it is only 1%–3% for sporadic tumors.[22],[23] In our study, three patients had recurrent myxomas (6.4%), two of them presented after 1 year of primary surgical excision, and one more after 3 years. All three patients were operated on elsewhere for primary tumors and had presented to us with recurrence. This recurrence rate is relatively higher as compared to previous studies probably because of the referral bias.

Study limitation

Data on the sporadic and familial nature of the disease was not available. We did not study the IL-6 levels and their correlation with symptoms, immunohistochemistry, and estrogens, and progesterone receptor status in the tumors were not analyzed. It was only a cross-sectional study and the improvement in symptoms with surgery was not evaluated and the follow-up data for recurrences was not available. The relatively low number of patients included in the present study is another and perhaps, the most important limitation.

  Conclusion Top

Cardiac myxomas are the most common benign tumors of the heart with vague symptoms but functionally malignant on rare occasions which warrants early surgery after the diagnosis. The clinical examination is often neglected but signs such as tumor plop give clues regarding the risk of embolization. Elevated serum CRP is associated with palpitations. Solid tumors have predominantly constitutional symptoms, whereas papillary tumors are prone to embolization. Neutrophilic infiltration of the tumor (not blood) has been associated with chest pain in myxoma tumors. Echocardiography gives significant information on the tumors, including site, mobility, morphology, numbers, and correlation of the symptoms which are due to hemodynamic disturbances caused by the tumor.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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