Epicardial Amyloidoma Mimicking Secondary Cardiac Lymphoma

Abstract

Background

Cardiac masses may represent a wide spectrum of neoplastic, inflammatory, and infiltrative diseases. Localized amyloid deposition (amyloidoma) is a rare entity that can closely mimic malignant cardiac infiltration.

Case Summary

A man with indolent B-cell lymphoma and monoclonal gammopathy was referred after incidental electrocardiogram abnormalities. Echocardiography showed an epicardial mass. Cardiac magnetic resonance demonstrated marked enhancement and increased extracellular volume, suspicious for secondary cardiac lymphoma or Erdheim-Chester disease. Positron emission tomography and bone scintigraphy were nondiagnostic. Surgical biopsy was performed and revealed Congo red–positive amyloid deposition associated with lambda-restricted plasma cells and a CD5-positive B-cell infiltrate.

Discussion

This case illustrates a rare epicardial amyloidoma mimicking malignant cardiac infiltration. It highlights the diagnostic challenges of atypical amyloid light-chain amyloidosis and the importance of early hematologic evaluation and histopathologic confirmation in patients with inconclusive imaging findings.

Take Home Messages

Localized amyloid deposition can be a rare presentation of amyloid light-chain amyloidosis. Comorbid or secondary conditions should not be overlooked.

Visual Summary

Visual Summary.

Epicardial Mass in a Patient With Indolent CD5-Positive B-Cell Lymphoma, IgG Lambda Monoclonal Gammopathy, and Echocardiographic Findings Suggestive of Amyloidosis

Differential diagnosis included cardiac amyloidosis, Erdheim-Chester disease, and secondary cardiac lymphoma. Following no significant change after rituximab therapy, surgical biopsy demonstrated extensive Congo red–positive amyloid deposition associated with a lambda-restricted plasma cell infiltrate and a small CD5-positive B-cell population, establishing the diagnosis of epicardial amyloidoma. The patient ultimately died from noncardiac causes. AL = amyloid light chain amyloidosis; ATTR = transthyretin amyloidosis; ECV = extracellular volume; LGE = late gadolinium enhancement; MRI = magnetic resonance imaging.

History of Presentation

A 78-year-old man with no prior cardiovascular history was referred for cardiology evaluation after an incidental finding of first-degree atrioventricular block and an anterior QS pattern on a preoperative electrocardiogram obtained before elective otolaryngologic surgery for inferior turbinate hypertrophy and chronic sinusitis.

At the time of evaluation, the patient was asymptomatic. Blood pressure was 128/72 mm Hg, and heart rate was 52 beats/min with regular rhythm. Jugular venous distension was noted. Cardiac auscultation revealed muffled heart sounds and a soft systolic murmur at the right upper sternal border. Lung auscultation demonstrated absent breath sounds at lungs bases. Mild hepatosplenomegaly and peripheral edema were noted.

Transthoracic echocardiography showed severe concentric left ventricular hypertrophy, most prominent at the basal segment of the posterolateral wall (17 mm). Global systolic function was preserved, but left ventricular strain was reduced (global longitudinal strain: 11%), with an apical sparing pattern and severely reduced strain in the inferolateral segments (Figure 1). A restrictive diastolic filling pattern was observed (Figure 2). The left atrium was severely dilated, and reservoir strain was markedly impaired (6%) (Figure 3). The aortic valve appeared thickened with sclerotic changes, resulting in moderate aortic stenosis (valvular area calculated by continuity equation: 1.3 cm²). Mitral leaflets fibrosis and chordal systolic anterior motion were present, with only mild mitral regurgitation. The right ventricle was of normal dimensions but hypokinetic (Figure 4). Moderate tricuspid regurgitation was observed, with estimated elevated pulmonary artery systolic pressure (systolic pulmonary artery pressure: 47 mm Hg). An epicardial mass infiltrating the right ventricular free wall was noted (Video 1, Video 2, Video 3). The inferior vena cava was plethoric. Circumferential pericardial effusion was present, without signs of hemodynamic compromise (Figure 5).

Figure 1.

Bull's-Eye Plot of Longitudinal Strain Demonstrating the Characteristic Apical Sparing Pattern (“Cherry-on-Top”)

The global longitudinal strain is reduced (−11.3%).

Figure 2.

Diastolic Evaluation Showing Restrictive Mitral Inflow Pattern

Evaluation showed an E/A ratio of 2.36 (Left), severely impaired E/e′ ratio of 42 (Middle), and marked systolic blunting of pulmonary vein flow (Right).

Figure 3.

Left Atrial Strain Evaluation Showing Marked Impairment of Reservoir Function (6%)

Figure 4.

Right Ventricular Strain Analysis Showing Reduced Free Wall Strain Values (12.8%)

Figure 5.

Hemodynamic Evaluation of Pericardial Effusion

Mitral (Left) and tricuspid (Right) inflow pattern showing only modest respiratory variation, not suggestive of tamponade physiology.

Past Medical History

The patient's medical history included turbinate hypertrophy with severe chronic sinusitis and was notable for an indolent CD5-positive lymphoma (possible marginal zone lymphoma), associated with an IgG lambda monoclonal component, with a serum kappa/lambda ratio of 0.56. The patient had never received chemotherapy or radiotherapy.

Differential Diagnosis

Given the history of lymphoma with monoclonal component, the findings of pericardial effusion associated with an epicardial infiltrative mass of unknown origin, and the severe concentric left ventricular hypertrophy with restrictive physiology and conduction system disease, the differential diagnosis included secondary cardiac involvement from lymphoma, Erdheim-Chester disease, and cardiac amyloidosis.

Cardiac involvement by systemic lymphoma was strongly considered given the patient's established low-grade B-cell lymphoproliferative disorder. Lymphomatous cardiac infiltration may present as an epicardial or atrioventricular groove mass, frequently encasing coronary arteries and infiltrating the right-sided chambers. Conduction abnormalities and pericardial effusion are also common manifestations.

Erdheim-Chester disease, a non–Langerhans cell histiocytosis, may involve the heart in up to 50% of cases,¹ typically manifesting with soft tissue infiltration, pericardial effusion, and coronary encasement.

Cardiac amyloidosis was strongly suspected based on the classic echocardiographic findings, progressive conduction system disease, and presence of IgG lambda monoclonal component.

Investigations

Cardiac magnetic resonance (CMR) was ordered to further characterize the epicardial mass. The scan confirmed concentric left ventricular hypertrophy (Videos 4 and 5). No signal abnormalities suggestive of myocardial edema were detected. On late gadolinium enhancement sequences, there was evidence of circumferential epicardial enhancement, primarily suggestive of infiltration by the epicardial lesion which appeared located at the atrioventricular groove, with sleeve-like extension along the course of the coronary arteries and surrounding the right ventricular free wall. The lesion appeared hyperintense on postcontrast T1-weighted sequences and markedly hyperintense on phase-sensitive inversion recovery sequences for late gadolinium enhancement assessment (Figure 6).

Figure 6.

Epicardial Mass (White Arrows) Appears Markedly Hyperintense on PSIR Sequences for Late Gadolinium Enhancement Assessment

PSIR = phase-sensitive inversion recovery.

Given the nonspecific tissue characterization of the epicardial mass, comprehensive multimodality imaging was undertaken.

A fluorodeoxyglucose (FDG) positron emission tomography scan showed FDG uptake at the level of the epi-pericardium. Of note, there was no abnormal uptake in the femoral region.

Restaging total-body computed tomography was performed, showing no significant progression of the oncologic disease except for the epicardial mass and pericardial effusion (Figure 7).

Figure 7.

Epicardial Lesion Shown Encasing the Right Coronary Artery (White Arrow)

Moderate pericardial effusion is also visible.

Finally, myocardial scintigraphy with bone-seeking tracers (99mTc) did not show cardiac uptake.

Management

After multidisciplinary consultation, biopsy of the epicardial mass was not performed because of the high surgical risk of the procedure. Instead, the patient underwent 2 cycles of immunotherapy with a monoclonal antibody (rituximab), after which a second CMR was performed.

At follow-up CMR, the pericardial effusion and the epicardial mass appeared stable. Marked late gadolinium enhancement was evident, with a substantially increased estimated extracellular volume fraction (approximately 95%) (Figure 8). The report suggested a diagnosis of cardiac amyloidosis associated with a highly extracellular epicardial mass, and cited a histologically confirmed case of “amyloidoma” with similar tissue characterization.²

Figure 8.

Circumferential Epicardial Mass (White Arrows) Showing a Very High Estimated Extracellular Volume Fraction (95%)

Findings were compatible with a localized extracellular matrix deposition referred to as “amyloidoma.”

The patient later experienced a syncopal episode due to advanced atrioventricular block, and was subsequently treated with definitive pacemaker implantation. Given the worsening clinical course and indefinite diagnosis, a surgical biopsy was performed.

Multiple irregularly marginated masses were identified, infiltrating the right atrioventricular groove and adjacent myocardium; these lesions appeared fibrocalcific and highly vascularized. A specimen of the mass was obtained and submitted for histopathological examination.

The patient had an unremarkable postoperative course and was discharged home shortly after. Postoperative echocardiography showed only trivial residual pericardial effusion.

Outcome and Follow-Up

The histological report from the biopsy of the epicardial mass became available 10 days after discharge and showed fibrous tissue lined by mesothelium, characterized by extensive deposition of amorphous fibrillary material with associated vascular wall thickening. Special stains included trichrome and Congo red, demonstrating extracellular deposition of amorphous material within the interstitium and vessel walls and, on Congo red staining, characteristic apple-green birefringence under polarized light. Amyloid subtyping by mass spectrometry was not performed. The lesion was predominantly composed of amyloid deposits, with a minor cellular component consisting of small lymphocytes forming perivascular nodular aggregates and morphologically mature plasma cells (Figure 9).

Figure 9.

Histological Images From the Biopsy of the Epicardial Mass

(A) Low-power hematoxylin and eosin stain demonstrating extensive extracellular eosinophilic amyloid deposition, representing the predominant component of the lesion, with an associated lymphoplasmacytic infiltrate. (B) Higher-power view of the boxed area in (A), highlighting the interface between the amyloid-rich area (left) and the lymphoplasmacytic infiltrate (right). Original objective magnification ×4 (A) and ×10 (B).

The B-lymphoid population was CD20+, CD79a+, PAX5+, CD5+, with partial CD23 expression; CD30–, CD15–, CD138–, and MUM1–.

The small T-lymphocyte population was CD3+, CD5+.

The mature plasma cell population was CD79a+, PAX5–, CD138+, MUM1+, and lambda light chain–restricted.

No evidence of epithelial neoplasia was noted (CKpan–, CK5/6–, p63–).

The overall morphologic findings were deemed suggestive of amyloidosis associated with a lambda-restricted plasma cell infiltrate and a CD5+ small B-cell population, consistent with the patient's prior history of low-grade B-cell lymphoma.

Given the histological findings suggestive of light chain (AL) amyloidosis, the patient was advised for additional diagnostic testing and hematologic consultation, but, unfortunately, a few days later he developed high fever and needed urgent hospitalization for complicated sinusitis, which ultimately led to death from purulent meningitis despite aggressive treatment.

Discussion

Cardiac amyloidosis most commonly presents as diffuse myocardial infiltration; in contrast, localized mass-forming amyloid deposition (“amyloidomas”) are rare and may mimic primary or secondary cardiac tumors, creating a significant diagnostic challenge.^2,3

In the present case, multimodality imaging revealed features concerning for infiltrative neoplastic disease, especially given the patient's history of indolent lymphoma. Erdheim-Chester disease was also considered because of the characteristic right atrioventricular groove involvement. However, the absence of FDG uptake in the epicardial lesion and the lack of systemic features typical of histiocytosis argued against this diagnosis.¹

CMR demonstrated marked late gadolinium enhancement and markedly increased extracellular volume within the epicardial lesion, suggesting extensive extracellular matrix expansion rather than highly cellular tumor infiltration. Nevertheless, imaging findings alone were insufficient to establish a definitive diagnosis. Histologic confirmation from surgical biopsy revealed Congo red–positive amyloid deposits associated with lambda-restricted plasma cells and a CD5-positive B-cell population, consistent with amyloid deposition associated with the patient's underlying lymphoproliferative disorder.

The mechanisms underlying amyloidoma formation remain incompletely understood but are thought to involve localized production of immunoglobulin light chains by clonal plasma cells or B lymphocytes within the affected tissue.² Additional factors likely contributing to this localized deposition include restricted lymphatic clearance, local tissue microenvironmental conditions favoring fibrillogenesis, and the presence of stromal elements that promote amyloid nucleation.⁴ This mechanism has been described in association with indolent B-cell lymphoproliferative disorders, including marginal zone lymphoma and lymphoplasmacytic lymphoma, in which localized monoclonal light-chain production can lead to tumor-like amyloid deposits.⁵

Despite reaching a final diagnosis of a rare disease through a complex clinical course, a few critical errors in the management of this case should be acknowledged. As highlighted in the recent document on AL amyloidosis by the American Society of Hematology,⁶ suggestive echocardiographic findings associated with a monoclonal gammopathy should have prompted immediate serum immunofixation, urine immunofixation, and serum free light chain assay analysis. In the scenario of positive biomarkers and diagnostic echocardiography, clinicians should proceed directly to tissue biopsy to avoid treatment delays. Myocardial scintigraphy with bone-seeking tracers is not recommended for the diagnosis of AL cardiac amyloidosis given its very low sensitivity in this subtype. Finally, once amyloid deposits are histologically confirmed, subtyping using a validated method (ideally mass spectrometry) is imperative to distinguish AL from other forms of amyloidosis.

In the present case, correct interpretation of the diagnostic algorithm would have anticipated diagnosis and treatment. However, the clinical picture was complicated by a very rare presentation of AL amyloidosis that sparked additional imaging testing and delayed biopsy.

Conclusions

In patients with monoclonal gammopathy or lymphoproliferative disorders, localized amyloid deposition should be considered in the differential diagnosis of cardiac masses. Multimodality imaging plays a critical role in guiding the diagnostic work-up, while histopathologic confirmation remains of utmost importance when imaging findings are inconclusive.

Funding Support and Author Disclosures

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

Take-Home Messages

• •Amyloidomas can be a rare presentation of AL amyloidosis.
• •Comorbid conditions should not be overlooked, as they may ultimately play a decisive role in the patient's clinical outcome.

Appendix

Video 1

Parasternal Long-Axis (PLAX) Cine-Loop Showing Marked Concentric Hypertrophy, Granular Sparkling Aspect of Myocardium, Moderate Pericardial Effusion, and Epicardial Mass on Right Ventricular Free Wall

Video 2

Off-Axis Parasternal Short-Axis (PSAX) View to Highlight the Epicardial Lesion, Which Appears in Close Contact With the Aortic Wall

Video 3

Right-Ventricle Focused Apical 4-Chambers View Showing the Hyperechogenic Epicardial Lesion Infiltrating the Right Ventricular Free Wall

Video 4

Steady-State Free Precession (SSFP) Short-Axis Cine-Loop Showing Marked Concentric Hypertrophy and Moderate Pericardial Effusion

Video 5

Steady-State Free Precession (SSFP) 4-Chamber Cine-Loop Showing Marked Concentric Hypertrophy and Moderate Pericardial Effusion