Severe Functional Tricuspid Stenosis Due to Phosphoglyceride Crystal Deposition Disease in Right Atrium.

This case report concerns a 72-year-old-female with severe functional tricuspid stenosis due to phosphoglyceride crystal deposition disease and a history of atrial septum closure and tricuspid valvuloplasty. Phosphoglyceride crystal deposition disease is extremely rare, and percutaneous transcatheter biopsy under intracardiac echocardiographic guidance proved to be useful for its diagnosis. (Level of Difficulty: Advanced.).

History of Presentation

A 72-year-old-female was admitted to the local hospital because of exertional dyspnea and lower-extremity edema. The patient had a chest x-ray and an increase in cardiothoracic index was described therefore a transthoracic echocardiogram (TTE) was requested. The patient was then transferred to our institution for further examination of the mass. Physical examination showed blood pressure of 134/62 mm Hg and a regular pulse of 84 beats/min. An electrocardiogram performed at our institution showed a normal sinus rhythm and inverted T-wave in V1 to V2. Laboratory data revealed elevated brain natriuretic peptide of 109 pg/mL, and TTE revealed a normal left ventricular (LV) ejection fraction of 61% and an LV end-diastolic volume of 62 mL and LV end-systolic volume of 24 mL, both normal. The iso-echoic solid mass measuring 35 × 40 mm was detected in the right atrium, which was attached to the interatrial septum and tricuspid annulus (Figure 1, Videos 1 and 2). The mass had also extended to the anterior and posterior leaflet of the tricuspid valve and aortic root (Figure 1, Videos 1 and 2). Furthermore, severe functional tricuspid stenosis caused by this mass was observed with a pressure half-time of 237 ms and mean pressure gradient of 9.2 mm Hg (Figure 2, Video 3). Transesophageal echocardiography revealed similar findings to those obtained with TTE (Figure 3, Video 4). Three-dimensional transesophageal echocardiography clearly showed narrowing of the right ventricular inflow tract as a result of the mass (Figure 4, Video 5). Contrast-enhanced computed tomography showed a solid enhanced mass in the right atrium which was attached to the interatrial septum to the tricuspid annulus (Figure 5, Video 6). Cardiac magnetic resonance imaging showed a mass in the right atrium with isointense on T1-weighted image and a mixture of isointense and hypointense areas on T2-weighted image (Figure 6). 18F-fluorodeoxy glucose–positron emission tomography imaging showed a significantly increased uptake only by the mass, which was suspected of being a primary malignant cardiac tumor (Figure 7).

Figure 1

Transthoracic Echocardiography

Transthoracic echocardiography showing an iso-echoic solid mass (white arrows) measuring 35 × 40 mm in the right atrium which was attached to the interatrial septum and tricuspid annulus. The mass also extended to the anterior and posterior leaflets of the tricuspid valve and aortic root. RA = right atrium; RV = right ventricle.

Figure 2

Transthoracic Echocardiography (Color Doppler)

Transthoracic echocardiography showing severe functional tricuspid stenosis due to this mass (white arrow) with a pressure-half time of 237 ms, and mean pressure gradient of 9.2 mm Hg. Abbreviations as in Figure 1.

Figure 3

Transesophageal Echocardiography

Ao = aortic route; RA = right atrium.

Figure 4

3-Dimensional Transesophageal Echocardiography

Three-dimensional transesophageal echocardiography showing narrowing of the right ventricular inflow tract (red arrow) caused by the mass. RA = right atrium.

Figure 5

Contrast-Enhanced Computed Tomography

Contrast-enhanced computed tomography showing the solid enhanced mass in the right atrium which was attached to the interatrial septum and tricuspid annulus. LV = left ventricle; other abbreviations as in Figures 1 and 3.

Figure 6

Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance imaging showed a mass in the right atrium with isointense on T1-weighted image (left) and a mixture of isointense and hypointense areas on T2-weighted image (right).

Figure 7

18F-Fluorodeoxy Glucose–Positron Emission Tomography

18F-fluorodeoxy glucose–positron emission tomography showing a significantly increased uptake only by the mass.

Learning Objectives

To understand the usefulness of differential diagnosis of intracardiac mass for patients with a previous history of cardiac surgery.

To gain a better understanding of the pathogenesis of phosphoglyceride crystal deposition disease.

Past Medical History

The patient had a previous history of atrial septum closure for an atrial septal defect and tricuspid valvuloplasty for tricuspid regurgitation, respectively, 26 years previously. The patient has also received methotrexate, salazosulfapyridine, famotidine, and risedronate sodium for rheumatoid arthritis for the previous 20 years.

Differential Diagnosis

The differential diagnosis of the mass in the right atrium based on the patient’s presentation included myxoma or lipoma if benignant, and malignant lymphoma or sarcoma if malignant. Because the mass extended to the normal surrounding tissue including tricuspid valve, tricuspid annulus, and aortic root, complete surgical resection of mass seemed to be impossible. Thus, we decided that a percutaneous transcatheter biopsy of the mass was required for a correct diagnosis.

Investigations

A 9-F sheath was inserted into the right internal jugular vein for the percutaneous transcatheter biopsy of the right atrial mass. Ten sequential samples were taken under the guidance of intracardiac echocardiography without any procedural complications (Figure 8, Video 7).

Figure 8

Percutaneous Transcatheter Biopsy Under Guidance of Intracardiac Echocardiography

Abbreviations as in Figure 1.

Management

Pathological examination using hematoxylin-eosin staining revealed that a granular substance 50 μm in size was surrounded by multinucleated giant cells (Figure 9A). In addition, it revealed that foreign body granulomas consisting of crystal deposition which characteristically showed an eosinophilic fibrinous rim and string-like crystals under polarized light (Figure 9B). Furthermore, this deposition showed positive when the gold hydroxamic acid method was used for screening for phosphoglyceride (Figure 9C). These findings led to a diagnosis of phosphoglyceride crystal deposition disease (PGDD). Our heart team came to the conclusion that complete surgical resection of the mass was impossible because of widespread invasion of the right-sided heart; therefore, careful periodic TTE will be performed.

Figure 9

Pathological Examination Findings

Pathological examination using hematoxylin-eosin staining revealed that a granular substance 50 mm in size was surrounded by multinucleated giant cells (A). Foreign body granulomas consisting of crystal deposition which characteristically showed an eosinophilic fibrinous rim and string-like crystals under polarized light (B). The deposition showed positive when the gold hydroxamic acid method was used for screening for phosphoglyceride (C).

Discussion

PGDD is a very rare disease defined as phosphoglyceride crystals deposited as tumors in the soft tissue or bone with no relation to the joint (1, 2, 3). Phosphoglycerides are a class of phospholipids, which include lecithin and cephalin, and constitute a major component of cell membranes. Phosphoglyceride crystal deposition disease is considered a lipid metabolic disorder, occurring predominantly in injured soft tissues and forming foreign body granulomas (1,4). PGDD sometimes results in the formation of large masses, which may be misdiagnosed as malignant tumors. Although little is known about the etiology and pathogenesis of PGDD, this deposition disease is apparently triggered by injury and subsequent macrophage aggregation, and histologically shows deposited crystals radiating from the cell membranes of epithelioid cells. This disease thus tends to occur at the sites of invasive procedures, including surgical sites (1,4).

To the best of our knowledge, only 14 cases of PGDD have been published up to June 2021 on PubMed. In most cases, phosphoglyceride crystal deposition disease occurred at sites susceptible to invasion due to a previous injury. In our case, phosphoglyceride crystal deposition might have occurred from atrial septum closure and tricuspid valvuloplasty scarring. Severely functional tricuspid stenosis due to the mass led to exertional dyspnea and lower-extremity edema so that careful echocardiographic follow-up was needed. Ours was the first case in which PGDD had a direct impact on hemodynamics.

Follow-Up

Before discharge, exercise stress echocardiography by means of supine bicycle exercise was performed to determine the association of functional severe tricuspid stenosis with exertional dyspnea. At a maximal work load of 25 W, mean trans-tricuspid pressure gradient increased to 15.1 mm Hg, and the increase in the peak tricuspid regurgitation pressure gradient from 14.6 mm Hg to 19.4 mm Hg. In addition, the decrease in right ventricular outflow tract velocity time integral changed from 11.8 to 12.9 cm. In addition, TTE was performed every 6 months after the diagnosis of PGDD because total resection of the mass could not be performed. In addition, based on the findings of exercise stress echocardiography we decided that no therapeutic intervention was required due to severe functional tricuspid stenosis caused by the mass. The size of the mass, 35 × 37 mm, remained unchanged 12 months after the diagnosis of PGDD. In addition, functional tricuspid stenosis with a pressure-half time of 208 ms, and mean pressure gradient of 6 mm Hg, had not become worse.

Conclusions

PGDD is an extremely rare condition, but it should be taken into consideration in the differential diagnosis of an intracardiac mass in patients with a previous history of cardiac surgery. Percutaneous transcatheter biopsy under guidance of intracardiac echocardiography proved to be useful for the diagnosis of PGDD.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.