Cardiac Sarcoidosis Presenting as a Biatrial Mass With Extensive Extracardiac Involvement

Abstract

Background

The diagnosis of cardiac sarcoidosis (CS) is often challenging, particularly in atypical cases.

Case Summary

This case involves a previously healthy 33-year-old woman who was found to have a biatrial mass and evidence of a diffuse inflammatory or neoplastic process on multimodality imaging. Percutaneous biopsy of the cardiac mass was performed, and histopathologic examination revealed granulomas consistent with CS.

Discussion

This case adds to the growing number of reports of CS manifesting as an intracardiac mass.

Take-Home Messages

The clinical presentation of CS is highly variable, and it may rarely manifest as an intracardiac mass. The diagnosis of cardiac sarcoidosis is often challenging, particularly in patients with atypical presentations. Indeterminate cardiac masses often require direct tissue sampling because the changes in treatment and prognosis are substantial.

Graphical Abstract

History of Presentation

A 33-year-old woman presented with sinus pressure, skin lesions, fatigue, and unintentional weight loss for 1 year following exposure to wildfire smoke. She was evaluated by otolaryngology for sinus pain and was ultimately considered for sinus surgery because of persistent symptoms and concern for a nasal mass. A preoperative electrocardiogram (ECG) revealed inferolateral T-wave inversions that prompted a transthoracic echocardiogram (TTE). The TTE was notable for a large, homogeneous mass involving the interatrial septum and moderate pericardial effusion; right and left ventricular systolic function was normal (Figures 1A and 1B). Cardiac magnetic resonance (CMR) confirmed the presence of a 25 mm × 46 mm × 59 mm mass involving the inferior aspect of the right and left atria and extending into the apical portion of the interatrial septum (Figures 1C and 1D). There was mild heterogeneous late gadolinium enhancement (LGE) of the mass and no LGE in the ventricles. CMR also showed prominent mediastinal and hilar lymphadenopathy.

Take-Home Messages

• •The clinical presentation of CS is highly variable, and it may rarely manifest as an intracardiac mass.
• •The diagnosis of CS is often challenging, particularly in patients with atypical presentations.
• •Indeterminate cardiac masses often require direct tissue sampling because the changes in treatment and prognosis are substantial.

Figure 1.

Multimodality Imaging of the Biatrial Mass

Transthoracic echocardiographic (A) apical 4-chamber and (B) parasternal short-axis views showing a mass in the location of the interatrial septum extending to the posterior aspects of the left and right atria (arrows). Cardiac magnetic resonance with steady-state free precession off-axis (C) 4-chamber and (D) sagittal images demonstrating the biatrial mass (arrows) and pericardial effusion. (E and F) A positron emission tomography scan showing a fluorodeoxyglucose-avid biatrial mass.

Further imaging and laboratory work-up were obtained. Computed tomography of the chest redemonstrated mediastinal and bilateral hilar lymphadenopathy, as well as numerous solid lung nodules and soft tissue encasing bilateral common carotid arteries. Abdominal imaging showed abdominopelvic lymphadenopathy, and a brain magnetic resonance imaging scan showed solid-appearing soft tissue in the bilateral nasal passages and orbits around the lacrimal gland. She was then evaluated by oncology, and a whole-body fluorine-18 fluorodeoxyglucose (FDG)–positron emission tomography (PET) scan was obtained. FDG PET revealed an FDG-avid cardiac mass (Figures 1E and 1F), as well as diffuse FDG-avid lymph nodes, subcutaneous lesions, osseous lesions, and pulmonary nodules. The working diagnosis at this time was cardiac angiosarcoma with metastatic lesions. Subsequently, a right supraclavicular lymph node biopsy was performed and demonstrated non-necrotizing granulomas, and a skin biopsy of a lesion on the left upper extremity revealed similar findings, raising the suspicion of sarcoidosis. Laboratory test results were notable for an elevated 1,25-dihydroxyvitamin D level, a low 25-hydroxyvitamin D level, an elevated angiotensin converting enzyme level, and an elevated lysozyme level.

The patient presented for a new outpatient cardiology appointment and was found to be in complete heart block (CHB), with a narrow junctional escape rhythm at 51 beats/min on ECG. She reported new dyspnea on exertion. She was admitted for expedited evaluation and management.

Past Medical History

Before the onset of symptoms, the patient had no medical or surgical history.

Differential Diagnosis

At this point, the differential diagnosis included an atypical presentation of cardiac sarcoidosis (CS) manifesting as a biatrial mass with extensive extracardiac involvement vs cardiac angiosarcoma with a diffuse, sarcoid-like reaction.¹ Additionally, the possibility of a non-Langerhans cell histiocytosis disease such as Rosai-Dorfman Disease (RDD) or Erdheim-Chester disease (ECD) was raised on the basis of clinical and radiographic evidence.

Investigations

A percutaneous biopsy of the mass was performed using fluoroscopic and transesophageal echocardiography guidance through a femoral access using a 6-F Argon Jawz (Argon Medical Devices) bioptome. Six tissue samples were taken from the right atrial aspect of the mass. Histopathologic examination of the specimens revealed confluent non-necrotizing granulomas (Figures 2A and 2B), and trichrome stain confirmed the presence of fibrosis. Results of microorganism stains were negative. Results of a molecular pathologic examination were negative for mutations associated with ECD.

Figure 2.

Non-Necrotizing Granulomas

(A) The biopsy specimen shows confluent non-necrotizing granulomas (hematoxylin and eosin stain; ×200 magnification). The granulomas were poorly formed and devoid of associated lymphocytic inflammation (naked granuloma). (B) A multinucleated giant cell (arrow) within the granulomatous inflammation (hematoxylin and eosin stain; ×400 magnification).

Management

On the basis of the atrial mass biopsy results, the diagnosis of CS was made. A permanent pacemaker was indicated for symptomatic CHB, and an implantable cardioverter-defibrillator (ICD) was inserted according to Heart Rhythm Society guidelines recommending an ICD in patients with CS and a permanent pacemaker indication.² The patient was started on immunosuppressive therapy 1 week after ICD insertion to allow healing and to minimize device infections. The initial immunosuppression regimen consisted of prednisone 30 mg daily for 3 months and methotrexate up-titrated every 2 weeks to reach 20 mg weekly. Given the extensive granulomas, she was planned for outpatient assessment for infliximab initiation.

Follow-Up

Six weeks after the patient began treatment, a repeat PET scan showed a significant reduction in FDG uptake of the biatrial mass (Figure 3A), as well as reduced uptake by the pulmonary, subcutaneous, and skeletal lesions. Several weeks later, the patient was readmitted with confusion and a change in mental status, which was eventually deemed steroid-induced psychosis; her symptoms improved with a reduction of the prednisone dose to 10 mg daily. She was then started on infliximab, with the ultimate goal of further decreasing the prednisone dose. Repeat CMR at 3 months showed complete resolution of the biatrial mass (Figure 3B). Follow-up ECGs and interrogation of her ICD revealed normal sinus rhythm with intact atrioventricular conduction.

Figure 3.

Imaging Following Treatment

(A) A positron emission tomography scan obtained after 6 weeks of treatment showing significantly reduced fluorodeoxyglucose uptake in the interatrial septum. (B) Cardiac magnetic resonance with a steady-state free precession 4-chamber image demonstrating complete resolution the biatrial mass after 3 months of treatment (artifact from the newly placed implantable cardioverter-defibrillator is noted toward the apex).

Discussion

This case represents a highly unusual presentation of CS manifesting as a large biatrial mass resulting from granulomatous infiltration of the interatrial septum and atrial walls causing CHB with extracardiac involvement of the lungs, thoracic and abdominal lymph nodes, skin, bones, eyes, sinuses, and carotid arteries. CS is traditionally characterized by patchy granulomatous infiltration of the myocardium that is typically not appreciated on a macroscopic level. However, there have been case reports of CS manifesting as a ventricular mass³ and as a right atrial mass.^4,5 Over the past year, 4 additional cases of CS manifesting as a right atrial or interatrial mass have been reported.6, 7, 8, 9 Of these more recent cases, all involve young, previously healthy women aged <50 years. These cases demonstrated varying responses to immunosuppressive therapy, and several involved surgical resection of the mass. The case discussed here is unique in 2 aspects. First, there was significantly more extracardiac involvement as compared with the other cases. Second, both the biatrial mass and the extracardiac lesions improved rapidly with immunosuppressive therapy alone, as evidenced by a follow-up PET scan 6 weeks after initiating treatment.

The diagnosis of CS is complex, particularly when histopathologic evidence is lacking. However, this case highlights the fact that even with histopathologic findings, the diagnosis can be challenging, especially if the presentation is atypical. In this case, the lymph node biopsy was pursued first and demonstrated non-necrotizing granulomas. According to the Heart Rhythm Society (HRS) diagnostic criteria, the histologic confirmation of extracardiac sarcoidosis, along with specific clinical and imaging findings, is sufficient for a clinical diagnosis of CS.² However, given the potential for a sarcoid-like reaction to coexist with malignant disease, it remained uncertain whether cardiac sarcoid could explain the imaging in its entirety or whether this represented angiosarcoma with a concomitant sarcoid-like reaction. Therefore, tissue from the mass itself was required for definitive diagnosis.

A non-Langerhans cell histiocytosis disease, such as RDD or ECD, was also considered on the basis of clinical and radiographic findings. RDD, also known as sinus histiocytosis, often affects the sinuses, whereas ECD commonly affects the long bones; both can involve the skin. Both RDD and ECD are known to manifest with atrial masses. The patient’s FDG PET scan, showing active inflammation in the cardiac mass, sinuses, bones, and skin, could be consistent with either histiocytosis or sarcoidosis. Differentiation depends heavily on histopathologic findings and the presence of associated mutations. This further highlights the complexity of CS diagnosis as a result of overlapping features with other diseases.

It is notable that the patient’s initial symptoms began shortly after exposure to wildfire smoke. Although the exact pathogenesis of sarcoidosis is unclear, it is thought to result from an abnormal immune response to an infectious or environmental antigen exposure in genetically predisposed individuals. There is a known association with combustible products, and studies have demonstrated high incidence and prevalence rates of sarcoidosis in firefighters and those exposed to World Trade Center dust.¹⁰ In retrospect, this aspect of the patient’s history provided a clue to the correct diagnosis.

The treatment of CS is largely based on expert consensus. Moderate-dose corticosteroids in combination with a steroid-sparing agent may be used initially in severe cases. In this patient, the decision was made to start both moderate-dose prednisone and methotrexate simultaneously on the basis of her extensive multiorgan and significant cardiac involvement.

Conclusions

This case of a young woman with CS manifesting as a large biatrial mass with extensive extracardiac involvement illustrates the highly variable nature of CS. Diagnosing CS is often complex, and atypical presentations such as in this patient pose additional diagnostic challenges. Although the lymph node biopsy demonstrated non-necrotizing granulomas, thereby fulfilling HRS criteria for CS, a tissue sample of the atrial mass was still necessary to differentiate cardiac sarcoidosis from angiosarcoma with a sarcoid-like reaction and ECD. Additionally, this case highlights similarities between sarcoidosis and histiocytosis diseases that may share clinical, radiographic, and histopathologic findings.

Funding Support and Author Disclosures

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