Diagnostic challenges of recurrent left atrial mass: a case report

Abstract

Background

Differential diagnosis of left atrial (LA) masses is challenging because there is a significant overlap in the epidemiological, clinical, and imaging characteristics. Even some histological features can be similar across different types of cardiac masses. Therefore, continuous case discussion between the clinician and the pathologist is essential for a correct diagnosis.

Case summary

We present a case of a patient with a history of cardiac surgery for LA tumour. Histology was compatible with thrombus, although no predisposing causes nor genetic or acquired thrombophilia were identified. After 14 years, the recurrence of LA mass was diagnosed with a routine echocardiography. A review of histological preparations from 2007 with immunohistochemistry techniques not available at that time (calretinin) was consistent with a myxoma. The patient underwent cardiac reoperation with LA mass and interatrial septum excision. Final diagnosis was compatible with a myxoma recurrence.

Discussion

Myxoma is the second most frequent benign primary cardiac tumour. Left atrial thrombi can occasionally mimic the typical echocardiographic appearance of a myxoma, and pathological features can sometimes overlap generating diagnostic confusion. Calretinin fixation is useful for differential diagnosis once it is only identified in myxomas but not in thrombi. Any discrepancy between clinical findings and histology should always mandate a review of histological preparations.

Learning points.

• Differential diagnosis of left atrial masses is challenging.

• Left atrial thrombi can sometimes mimic the typical echocardiographic appearance of myxoma, and histological findings can sometimes overlap between the two entities.

• Continuous case discussion between the clinician and the pathologist is essential. Any should mandate a review of histological preparations.

Introduction

The differential diagnosis of left atrial (LA) masses can be challenging.^1,2 Epidemiological, clinical, and imaging characteristics may overlap significantly, and therefore, obtaining a histopathological specimen is the gold standard for definitive diagnosis.² However, it must be interpreted on the background of the patient’s clinical presentation, as some features can be identical across different types of cardiac masses. Continuous case discussion between the clinician and the pathologist is therefore essential for a correct diagnosis.

Timeline

Time	Event
October 2007	Cardiac surgery for left atrial (LA) tumour. Pathology compatible with organized thrombus. Workup for acquired or genetic causes of thrombophilia was negative.
May 2021	De novo LA mass in routine transthoracic echocardiography.
May 2021	Transoesophageal echocardiography (TOE) showing mobile and pedunculated LA mass attached to the interatrial septum. Started on oral anticoagulation.
July 2021	Re-evaluation TOE after 6 weeks of oral anticoagulation therapy showing no significant size reduction.
July 2021	Review of 2007 histopathological preparations. Positive for calretinin.
August 2021	Cardiac reoperation with excision of LA tumour. Pathology compatible with cardiac myxoma.
October 2022	The patient maintains regular follow-up and free of recurrence on echocardiographic assessment.

Case presentation

In 2008, Calé et al. reported the clinical case of a 47-year-old female patient with no past medical history presenting with a large (57 × 33 mm) LA tumour attached to the fossa ovalis by a stalk (Figure 1A).¹ Although an initial suspicion of an atrial myxoma (for both echocardiographic and macroscopic characteristics), the histopathological examination was consistent with an organized thrombus (Figures 1BandC). Since surgical resection, in 2007, she maintained regular clinical and echocardiographic follow-up. After extensive investigation, no causes of genetic or acquired thrombophilia (such as antiphospholipid syndrome) were identified. The patient was otherwise healthy and after a brief period of oral anticoagulation with warfarin, she stopped taking medication.

Figure 1.

(A) Left atrial polypoid and pedunculated mass (57 × 33 mm) attached to the interatrial septum and protruding into the mitral valve in the preoperative transthoracic echocardiography (arrow). (B) Macroscopical aspect of the mass excised in 2007. (C) Haematoxylin–eosin (H&E) preparation of the left atrial mass, showing an organized thrombus.

In 2021, she was referred for further evaluation after an incidental finding of a de novo LA mass in routine transthoracic echocardiography (TTE) that was not present in the last examination 4 years earlier. There was no history of atrial fibrillation, stroke, venous thromboembolism, or heart failure. At the consultation, the patient was asymptomatic, and the physical examination was unremarkable. She was afebrile and with normal breathing rate, her blood pressure was 115/70 mmHg, and the heart rate was 72 bpm. Cardiopulmonary auscultation revealed normal heart and chest sounds. The abdomen was non-tender to palpation and there was no peripheral oedema. Laboratory tests including complete blood count, renal and hepatic function, and inflammatory markers were normal. The 12-lead electrocardiogram revealed sinus rhythm without conduction or repolarization disturbances.

Transthoracic echocardiography showed a mobile LA mass attached to the interatrial septum, normal biventricular function, and no significant valvular heart disease (Figure 2). For better characterization, transoesophageal echocardiography (TOE) was performed. It showed a mobile and pedunculated filamentous mass in the LA (dimensions of 13 × 11 mm), attached to the interatrial septum (see Supplementary material online, Videos S1 and S2). There was no spontaneous echo contrast or LA appendage thrombus. Given the previous diagnosis of LA thrombus, a recurrency was initially considered to be the most likely diagnosis and rivaroxaban (20 mg daily) was started. A re-evaluation of TOE after 6 weeks of effective anticoagulation showed no significant size reduction (see Supplementary material online, Video S3).

Figure 2.

Incidental de novo left atrial mass attached to the interatrial septum in the follow-up transthoracic echocardiography in 2021 (arrow).

Considering the discrepancy between the clinical findings and previous histological diagnosis, a review of the histopathological preparations from the 2007 excised mass was requested. It was consistent with a large and organized thrombus, with small islets of myxoid stroma and spindle cells, initially interpreted as myxoid degeneration (Figure 3A). Using immunohistochemistry techniques not routinely available in the hospital’s Pathology Lab in 2007 (calretinin), the tumour was rediagnosed as a cardiac myxoma (Figure 3B).

Figure 3.

(A) H&E histological preparation review of the left atrial mass excised in 2007 showing a large, organized thrombus with neoangiogenesis and islets of myxoid stroma (star). (B) Calretinin immunohistochemistry fixation, consistent with cardiac myxoma (brown).

The patient underwent cardiac reoperation. The LA mass was successfully resected via conventional median sternotomy. Following cardiopulmonary bypass and right atriotomy, the complete resection of both the tumour and the adjacent interatrial septum was performed. The resulting atrial septal defect was repaired using a bovine pericardial patch. Direct macroscopic inspection and histopathological examination with calretinin immunohistochemistry were consistent with cardiac myxoma (Figure 4).

Figure 4.

H&E (A) and calretinin (B) preparations of the tumour excised in 2021, consistent with cardiac myxoma.

The postoperative period was uneventful, and the patient was discharged after 5 days. At 1 year of follow-up, she remains asymptomatic and not taking any medication. The re-evaluation of TTE shows no signs of recurrence.

Discussion

Despite being rare in the general population, myxomas are the second most frequent benign primary cardiac tumours.³ They occur more often in females and are most commonly found in the LA at the fossa ovalis.² On TTE, myxomas typically appear as a mobile mass of variable size attached to the endocardial surface by a stalk.² Incidental discovery on imaging examinations is not uncommon, although many patients may experience embolic events, and obstructive or constitutional symptoms.³ Cardiac myxomas can be morphologically classified into polypoid (smooth, lobulated surface) and papillary (villiform architecture), the latter being more frequently associated with embolic phenomena. In both cases, the diagnostic hallmark is the presence of spindle-shaped cells (myxoma cells) embedded in a myxoid matrix.^2,3 Complete surgical resection is associated with the best clinical outcome, and the annual TTE follow-up is recommended given that up to 15% can recur, most frequently at the site of the original tumour.^2,3

Left atrial thrombus can occasionally present as a mobile and pedunculated structure mimicking the typical echocardiographic appearance of a myxoma.⁴ Despite being usually associated with thrombophilia, atrial fibrillation or low output conditions, thrombi can sometimes exist in the absence of such classical predisposing factors.^2,4 Imaging modalities such as the use of ultrasound-enhancing agents (UEA) in echocardiography and cardiac magnetic resonance (CMR) are useful for differential diagnosis and in guiding subsequent management.² Unlike myxomas, thrombi are avascular structures and therefore do not perfuse with UEA echocardiography nor with first-pass perfusion CMR.² Cardiac magnetic resonance is also useful for anatomic and histopathological characterization, although its accuracy in diagnosing highly mobile intra-cardiac masses is hindered by its limited temporal resolution.^2,3

In some cases, the histopathological differential diagnosis between thrombus and myxoma can also be challenging. Despite being unusual, myxoid-like features in organized thrombi have been previously reported, especially when only small islets of myxoid stroma are identified on the background of fibrinous thrombus material.⁵ In addition, organizing thrombotic changes can be commonly found on the surface of cardiac myxomas, potentially misleading the diagnosis.⁶

In this case, the absence of classical risk factors and lack of clinical response to systemic anticoagulation raised high suspicion for an alternative diagnosis, even if the prior histological examination was compatible with a thrombus. Calretinin fixation, which is only identified in cardiac myxomas but not in cases of thrombi, was essential for the final diagnosis.⁷

Conclusions

Continuous case discussion between the clinician and the pathologist is essential. Any discrepancy between clinical findings and histology should always mandate a review of histological preparations.

Lead author biography

28 years old Cardiology Resident at Hospital de Santa Cruz, Lisbon, Portugal.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports.

Data availability

All data underlying the results are available as part of the article.