Review article
Cardiac myxoma induced paraneoplastic syndromes: A review of the literature

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Abstract

Background

Atrial myxomas are the most common benign tumors of the heart and may present with a wide variety of symptoms. Although 45% of patients present with neurological symptoms, a diverse range of systemic symptoms also occur.

Methods

A systemic review of the literature related to the diagnosis, treatment, pathogenesis, and symptoms associated with atrial myxomas was performed.

Results

Here we summarize the current state of understanding about myxoma pathogenesis and treatments are described. We review the common and rare local and systemic effects of myxomas. Additionally, we review the paraneoplastic and metastatic potential of myxomas.

Conclusions

A better understanding of the diverse disease presentations, paraneoplastic syndromes, and side effects of cytokine abnormalities stemming from myxomas will aid the physician in earlier detection and monitoring of disease recurrence.

Introduction

Primary cardiac tumors are very rare with an incidence ranging from 0.0017% to 0.19% in one autopsy series [1]. Atrial myxomas are the most common cardiac tumors and comprise 50% of all benign cardiac tumors [2], [3]. In this review, we will review all aspects of myxomas including location and nature of myxomas, pathogenesis, diagnosis, and treatment. Further discussion will include the metastatic potential and paraneoplastic manifestations that complicate myxomas.

The name myxoma is derived from its appearance as a cell-poor, myxoid neoplasm with a mucopolysaccharide-rich extracellular matrix. Myxomas range in size from 1 to 15 cm and are typically round, oval, or lobulated with a smooth surface and a narrow pedicle attaching to the cardiac tissue [4]. Broad-based features and a frond-like appearance have also been reported [4].

The most common locations for myxomas are the left atrium (60–75%), the right atrium (20–28%) and, rarely in both atria and ventricles. Typically, myxomas arise close to the fossa ovalis of the interatrial septum, although a few arise from free walls of the atria or from atrioventricular valve leaflets [5]. There is a 2:1 female predominance and diagnosis is typically between 50 and 70 years of age [6].

Although atrial myxomas occur sporadically, at least 10% of the cases are familial, the most common of which is the Carney syndrome [7]. This autosomal dominant syndrome consists of multiple cardiac myxomas, a variety of pigmented skin lesions, extra-cardiac tumors and melanotic schwannomas. Patients with Carney's triad are usually younger and more likely to have myxomas outside the left atrium. Carney syndrome is also associated with increased risk of myxoma recurrence, approaching 25%, after tumor resection [8]. Mutations in the tumor suppressor gene, protein kinase A (PKA) type-1 regulatory subunit (R1A) PRKAR1A, occur in > 50% of cases while linkage to chromosome 2p16 occurs in other families [9], [10], [11], [12].

The mechanisms by which atrial myxomas produce symptoms include constitutional symptoms, systemic embolization, and mitral valve obstruction. Although 10% of patients may be asymptomatic, most patients present with constitutional symptoms such as fever, weight loss, weakness or myalgias [6]. Cardiac symptoms usually manifest as dyspnea, palpitations or syncope. These symptoms are related to obstruction to left ventricular inflow or elevated left atrial pressures. Neurological manifestations are frequent and have been reported in 25–45% of cases [13]. The neurological signs and symptoms are usually a result of embolization. Tumor mobility, not size, appears to be related to embolic potential. Rarely, neurological complications may be due to embolized tumor fragments instead of surface thrombi [14], [15].

Section snippets

Pathogenesis

There are two main gross anatomical types of atrial myxomas, a solid type that is firm and smooth and a gelatinous type that is soft and friable [16]. Shimono et al. found that clinical presentation correlated with the gross tumor appearance [17]. Patients with solid tumors were more likely to present with congestive heart failure symptoms while patients with gelatinous tumors were more likely to present with cerebral and peripheral embolization [17]. Solid myxomas are highly vascular tumors

Diagnosis and treatment

Until 1977 when echocardiography became readily available, a means of noninvasive diagnosis was unavailable. Previously atrial myxomas had been described postmortem, as was the case with the first atrial myxoma described in the literature by Goldberg et al. in 1952 [29]. Even today, the diagnosis of atrial myxoma can be challenging given the variety of nonspecific symptoms patients may have. Echocardiography remains the most frequently used imaging modality to detect atrial myxomas.

Metastatic myxomas

The metastatic potential of cardiac myxomas and its true existence is still a matter of debate. Traditionally, myxomas are considered to be a benign neoplasm with spread to extracardiac sites considered to be a result of embolic phenomena. There are, however, a number of cases in the literature which reflect possible true metastatic potential and this should be considered a rare complication of myxomas.

Metastatic myxomas have been documented in the lungs, bones, soft tissues and even

Paraneoplastic manifestations

Paraneoplastic syndromes have been speculated to be associated with myxomas in several case reports (Table 2). A wide range of cutaneous manifestations appears to be related to cardiac myxomas including Raynaud's phenomenon, livedo reticularis, splinter hemorrhages, non-blanching lesions of fingertips, violaceous eruptions with peripheral cyanosis and toe necrosis [55], [56], [57], [58], [59]. More severe manifestations have also been reported including vasculitis, demyelinating neuropathy, and

Conclusion

Atrial myxomas are a diverse cardiac tumor with a wide spectrum of symptoms that often leads to significant delays in diagnosis. Traditionally many of the symptoms could be attributed to systemic embolization of either surface emboli or tumor fragments. Furthermore, many cardiovascular symptoms are secondary to alterations in the hemodynamics produced by these tumors. Although these remain viable explanations for many of the symptoms produced by atrial myxoma, there also appears to be other

Learning points

  • Cardiac myxomas present with a wide variety of cardiac, neurological, and systemic symptoms.

  • Neurological manifestations are the most common sign of myxomas and often result from embolization of surface thrombi.

  • Cardiac myxomas may metastasize by tumor fragment embolization and can be found in remote locations including bone, brain, and muscle.

  • Cardiac myxomas may present with paraneoplastic syndromes likely related to abnormal cytokine production from the tumor.

Conflict of interest statement

None of the authors have any actual or potential conflict of interest financial, personal, or otherwise that could influence or be perceived to influence their work.

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