A Rare Intra-Atrial Cyst of Vascular Origin

Abstract

Background

Intra-atrial cysts are rare and often mistaken for neoplastic lesions. Vascular-origin cysts are even more uncommon. Limited genetic data hamper understanding of their pathogenesis and management.

Case Summary

A 64-year-old man was referred for evaluation of an incidentally detected right atrial mass. Echocardiography suggested a hemorrhagic cyst. Surgical excision and histopathology confirmed a vascular malformation, with CD34 and smooth muscle actin positivity, elastic fibers demonstrated on special staining. Genetic testing revealed a pathogenic TSC2 mutation. The patient underwent successful mass resection and tricuspid annuloplasty with uneventful recovery.

Discussion

This case highlights a rare intra-atrial blood cyst associated with TSC2 mutation, suggesting a genetic basis for vascular malformations. TSC2 screening may help differentiate benign from malignant cardiac lesions, especially those with hemorrhagic features. In selected cases, image-guided aspiration could be a less-invasive alternative to surgery.

Take-Home Message

TSC2 genetic testing may improve diagnosis and guide treatment strategies for atypical cardiac vascular lesions.

Graphical Abstract

History of Presentation

A 64-year-old man was referred for further evaluation and management of a right atrial mass that had been incidentally discovered during a routine health examination 1 week earlier. The patient was asymptomatic at the time of detection.

Take-Home Messages

• •Genetic testing should be considered in the evaluation of atypical or unexplained cardiac masses, especially when imaging and pathology suggest a non-neoplastic vascular origin.
• •Identifying pathogenic mutations such as TSC2 may not only aid diagnosis but also inform future therapeutic decisions and surveillance strategies.

Past Medical History

The patient had no history of hypertension, diabetes mellitus, or other known cardiovascular risk factors. His medical history was otherwise unremarkable.

Differential Diagnosis

The differential diagnosis was broad and included cardiac myxoma, hemangioma, organized thrombus, and metastatic malignancies. These possibilities were considered based on the imaging features and the atypical location of the mass.

Investigations

Transthoracic echocardiography (Video 1) revealed a mixed-echogenicity mass in the right atrium, measuring 4.21 cm × 4.86 cm, with central punctate calcification. The mass was attached to the posteroinferior aspect of the interatrial septum near the coronary sinus and prolapsed into the right ventricle during diastole. Moderate to severe tricuspid regurgitation with annular dilation was also observed. Contrast-enhanced ultrasound demonstrated no microbubble perfusion within the mass, consistent with a nonvascularized cystic lesion; however, the capsule became more clearly defined (Figure 1).

Figure 1.

Echocardiographic Imaging of the Right Atrial Mass

(A) Transthoracic echocardiography reveals a mixed-echogenic mass within the right atrium, containing central punctate calcification. (B) During diastole, the mass prolapses into the right ventricle. (C) The mass, measuring 4.21 cm × 4.86 cm, is attached to the posteroinferior portion of the interatrial septum and lies adjacent to the coronary sinus. (D) Contrast-enhanced ultrasound demonstrates no microbubble perfusion within the cystic mass, although the capsule is more clearly defined. Yellow star: right atrium; yellow arrow: mass in the right atrium. LA = left atrium; RV = right ventricle; TV = tricuspid valve.

Management

In light of the cardiac mass, coexisting valvular disease, and the patient's reduced exercise capacity, surgical intervention was advised. Following the initiation of cardiopulmonary bypass, a right atriotomy was performed, exposing a dark blue, pedunculated mass measuring 5 cm × 6 cm (Figure 2). The mass originated from the interatrial septum. Complete resection of the lesion was achieved, followed by repair of the septal defect. Tricuspid valve annuloplasty was concurrently performed due to significant annular dilation and regurgitation. The patient was weaned off cardiopulmonary bypass without complications.

Figure 2.

Intraoperative Views of the Right Atrial Mass

(A) Preoperative transesophageal echocardiography shows a mixed-echogenic mass in the right atrium. (B to D) Intraoperative findings show a dark blue mass, which was completely excised during surgery. Yellow star: right atrium; yellow arrow: mass in the right atrium. RV = right ventricle; AS = atrial septum.

Histopathology and Immunohistochemistry

Histological evaluation confirmed the lesion to be a vascular malformation. Immunohistochemical staining was positive for cluster of differentiation 34 (CD34) and smooth muscle actin, both characteristic markers of vascular tissue (Figure 3). Elastic fiber staining further confirmed vascular structural involvement, reinforcing the diagnosis of a vascular-origin cystic lesion.

Figure 3.

Histopathologic Evaluation of the Cystic Mass

(A) Histologic analysis reveals a vascular malformation. (B) Immunohistochemical staining is positive for CD34. (C) SMA staining is also positive, indicating vascular smooth muscle components. (D) Special elastic fiber staining supports the diagnosis of a vascular malformation. CD34 = cluster of differentiation 34; SMA = smooth muscle actin.

Genetic Testing

Genetic sequencing identified a pathogenic tuberous sclerosis complex 2 (TSC2) c.724A>G variant (Figure 4). This mutation affects the tuberin protein, a critical regulator of cell growth and angiogenesis, via the mechanistic target of rapamycin (mTOR) signaling pathway. Dysregulation of this pathway is known to promote vascular malformations and tumor-like growths, providing a plausible genetic explanation for the development of this atypical intra-atrial lesion.

Figure 4.

Genetic Testing Identifying a TSC2 c.724A>G Mutation

Genetic analysis identified a TSC2 c.724A>G variant located on chromosome 16p13.3. This mutation is associated with impaired tuberin function, resulting in dysregulated mechanistic target of rapamycin (mTOR) signaling and contributing to vascular malformation pathogenesis.

Outcome and Follow-Up

At 1 month postoperatively, follow-up echocardiography confirmed complete resection of the atrial mass, with no residual lesion. The tricuspid valve annulus appeared normal, and valvular function had returned to physiological levels.

Discussion

Cardiac masses are rare and encompass a broad spectrum of etiologies, including benign tumors (eg, myxomas, lipomas), malignant neoplasms, and non-neoplastic lesions such as thrombi or cysts.¹ Multimodal imaging—including echocardiography, computed tomography, and magnetic resonance imaging—plays a pivotal role in their diagnosis, characterization, and management.

In the present case, a right atrial mass was initially presumed to be a hemorrhagic cyst based on imaging. However, histopathological examination confirmed it to be a vascular malformation, with subsequent genetic testing identifying a TSC2 mutation. The TSC2 gene, located on chromosome 16p13.3, encodes tuberin, which forms a functional complex with hamartin (encoded by TSC1), to negatively regulate the mTOR signaling pathway.² The TSC1/2 heterodimer inactivates the Ras homolog enriched in brain guanosine triphosphate, thereby inhibiting mTOR complex 1 (mTORC1)—the central regulator of cellular growth and angiogenesis. Loss-of-function mutations in TSC2 disrupt this inhibitory function, leading to persistent mTORC1 activation. As a downstream effect, angiogenic factors such as vascular endothelial growth factor are upregulated, promoting the formation of abnormal vasculature and contributing to the development of vascular malformations (Figure 5).^2,3

Figure 5.

Schematic Illustration of mTOR Pathway Dysregulation in Tuberous Sclerosis Complex

Diagram of the mTOR signaling pathway, highlighting its role in angiogenesis and vascular remodeling. TSC2 mutations cause mTOR hyperactivation, which promotes upregulation of angiogenic factors such as VEGF, potentially leading to vascular malformations. GDP = guanosine diphosphate; GTP = guanosine triphosphate; mTOR = mechanistic target of rapamycin; Rheb = Ras homolog enriched in brain; TSC2 = tuberous sclerosis complex 2; VEGF = vascular endothelial growth factor.

Thus, the molecular mechanism underlying the TSC2 mutation provides a biologically plausible explanation for the vascular origin of the lesion observed in our patient.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in either the TSC1 or TSC2, characterized by the development of benign tumors (hamartomas) in multiple organs, including the brain, kidneys, skin, and heart.^3,4 Cardiac manifestations typically include rhabdomyomas, especially in pediatric patients. These tumors are often asymptomatic but may cause arrhythmias or heart failure and usually regress spontaneously.¹ In contrast, cardiac vascular malformations, such as the one identified in this case, are exceedingly rare and not commonly reported in association with TSC.

The association between TSC2 mutations and vascular malformations is increasingly recognized. Notably, mutations in other components of the phosphatidylinositol 3-kinase-protein kinase B-mTOR signaling axis—such as PIK3CA, which encodes the catalytic subunit of phosphatidylinositol 3-kinase—have also been implicated in vascular anomalies, including venous malformations.⁵ These genetic alterations converge on shared downstream pathways, particularly mTORC1 activation, suggesting a common pathogenic mechanism that may underlie both syndromic and sporadic forms of vascular malformations. Importantly, this mechanistic overlap has opened new avenues for targeted therapies that modulate mTOR signaling in affected patients.

We hypothesize that the right atrial hemorrhagic cyst observed in our patient resulted from a vascular malformation driven by the TSC2 mutation. The loss of mTOR inhibition likely caused dysregulated angiogenesis and abnormal vascular remodeling within the atrial wall, culminating in cyst formation. This case highlights a rare cardiac manifestation of TSC and supports the role of mTOR dysregulation in the pathogenesis of vascular cysts.

Surgical Management and Approaches

While conservative management may be appropriate for small, asymptomatic intracardiac hematocysts, surgical resection is generally indicated when the lesion causes hemodynamic compromise, embolic risk, or valvular dysfunction. The standard surgical approach involves median sternotomy under cardiopulmonary bypass. However, minimally invasive techniques, such as video-assisted thoracoscopic surgery or the AngioVac system (AngioDynamics), have emerged as viable alternatives in select patients, particularly when open surgery is contraindicated or deemed as high risk.^6,7

The AngioVac system utilizes a veno-venous extracorporeal circuit to aspirate intracardiac masses via percutaneous access, allowing for debulking of thrombi, tumors, or cystic lesions without the need for sternotomy.^7,8 In our case, the large size and anatomical complexity of the mass necessitated open surgical resection. Nevertheless, for smaller or peripherally located vascular cysts, minimally invasive strategies may offer safer, less-invasive alternatives.

We propose that in patients presenting with a mixed-echogenicity cardiac mass on transthoracic echocardiography, characterized by well-defined contents with central punctate calcification, absence of enhancement on contrast-enhanced ultrasound, and a known TSC2 mutation, a vascular-origin cyst—such as a hemorrhagic vascular malformation—should be strongly considered in the differential diagnosis. In such cases, ultrasound-guided percutaneous aspiration may be a viable option for cyst decompression and symptom relief, potentially avoiding thoracotomy. However, the safety, feasibility, and long-term efficacy of this approach require validation through prospective studies. This may provide new insights for future diagnostic and therapeutic strategies.

Conclusions

We present a rare case of a right atrial hemorrhagic cyst associated with a TSC2 gene mutation, supporting the hypothesis that dysregulated mTOR signaling contributes to the development of atrial vascular malformations. This case emphasizes the diagnostic value of combining genetic analysis with histopathological evaluation in identifying the underlying etiology of atypical cardiac masses and guiding appropriate management.

Visual Summary.

Case Timeline

Date	Clinical Event
Day 0	Referred to our institution for evaluation of a right atrial mass of undetermined origin
Day 1	Repeat echocardiography revealed a right atrial hemorrhagic cyst with moderate-to-severe tricuspid regurgitation.
Day 2	Underwent right atrial tumor resection with concomitant tricuspid valve annuloplasty.
Day 8	Echocardiography demonstrated complete resection of the right atrial tumor with visualization of the annuloplasty ring and competent tricuspid valve function

Funding Support and Author Disclosures

This study was funded by the Tianjin Education Commission Key Project (No. 2023ZD007), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-029A), and National Natural Science Foundation of China (82470527). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Video 1

Transthoracic Echocardiography Demonstrating the Right Atrial Mass

Transthoracic echocardiographic video showing a right atrial mass with mixed echogenicity and central punctate calcification. Yellow arrow: mass in the right atrium.