Should a pericardial effusion in an older adult patient with smoldering myeloma (precursor to multiple myeloma) be checked for amyloid deposits?

Should Pericardial Effusion in Smoldering Myeloma Be Checked for Amyloid?

Yes, the pericardial effusion should absolutely be evaluated for amyloid deposits through pericardiocentesis with comprehensive fluid analysis including Congo red staining, mass spectrometry-based amyloid typing, and cytology to rule out both AL amyloidosis and direct plasma cell infiltration. 1, 2

Rationale for Testing

High-Risk Clinical Context

• Patients with smoldering myeloma have an underlying plasma cell dyscrasia that places them at significant risk for AL (light chain) amyloidosis, which occurs in up to 50% of patients with plasma cell disorders and frequently involves cardiac structures including the pericardium 1
• Pericardial involvement in plasma cell dyscrasias has three primary etiologies: AL amyloidosis (most common), direct plasma cell infiltration, or bleeding diathesis—all of which require different management approaches 3, 4
• Cardiac amyloidosis carries a drastically poor prognosis with median survival of only 4 months once heart failure symptoms develop, making early detection critical for mortality outcomes 1

Diagnostic Imperative

• The American College of Cardiology emphasizes that amyloid deposits in the pericardium can result in pericardial effusion formation, and identifying the precursor protein type dictates treatment strategy and prognosis 1, 2
• Tissue diagnosis with Congo red staining followed by mass spectrometry-based typing (LC-MS/MS) is the gold standard with 88% sensitivity and 96% specificity for identifying the amyloid precursor protein 2
• Pericardial fluid should be sent for comprehensive analysis including Congo red staining, mass spectrometry for amyloid typing, cytology to detect plasma cell infiltration, and routine chemistry/microbiology 2, 3

Comprehensive Workup Required

Concurrent Systemic Evaluation

Even if pericardiocentesis is performed, you must simultaneously evaluate for systemic plasma cell disorder and amyloidosis:

• Serum free light chain (sFLC) assay, serum immunofixation electrophoresis (SIFE), and urine immunofixation electrophoresis (UIFE) are mandatory—do not rely on serum protein electrophoresis alone as it misses nearly 50% of cases 1, 5, 2
• Bone marrow aspiration and biopsy with Congo red staining to assess for plasma cell percentage, clonal populations, and amyloid deposits 1, 2
• Echocardiography to assess for cardiac amyloid features: ventricular wall thickening, diastolic dysfunction, reduced QRS voltage on ECG despite wall thickening, and characteristic late gadolinium enhancement patterns 1
• Consider technetium-99m bone scintigraphy (PYP/DPD scan) which can non-invasively diagnose ATTR cardiac amyloidosis if no monoclonal protein is detected 2

Critical Diagnostic Pitfall

• Over 10% of patients with monoclonal gammopathy can have ATTR (transthyretin) amyloid deposits rather than AL amyloidosis, so you cannot assume AL amyloidosis based solely on the presence of smoldering myeloma—definitive amyloid typing via mass spectrometry is essential 2
• If any monoclonal protein is detected (even MGUS-level), endomyocardial biopsy may be necessary to definitively distinguish between AL and ATTR cardiac amyloidosis, as both can coexist 2

Alternative Etiologies to Exclude

Direct Plasma Cell Infiltration

• Pericardial involvement from direct plasma cell infiltration is rare but documented, typically occurring at late or terminal disease stages 3, 4, 6
• Cytology and immunocytochemistry of pericardial fluid can identify malignant plasma cells—this was the presenting manifestation in reported cases and carries a universally fatal prognosis without response to chemotherapy 3, 4
• One case series showed that plasma cell infiltration of the pericardium led to progressive disease and death in all three patients despite chemotherapy and supportive measures 3

Clinical Algorithm

1. Perform pericardiocentesis if hemodynamically indicated or if moderate-to-large effusion present 1
2. Send pericardial fluid for: Congo red staining, mass spectrometry (LC-MS/MS) for amyloid typing, cytology with immunocytochemistry for plasma cells, routine chemistry/cell count, and microbiology 2, 3, 4
3. Simultaneously obtain: sFLC assay, SIFE, UIFE, bone marrow biopsy with Congo red staining, and echocardiography 1, 5, 2
4. If Congo red positive: Mass spectrometry definitively identifies AL vs ATTR vs other amyloid types 2
5. If plasma cells identified: This represents direct malignant involvement requiring urgent hematology consultation and systemic chemotherapy 3, 4
6. If both negative: Consider other etiologies (infection, uremia, autoimmune) but maintain high suspicion given the plasma cell dyscrasia 1

Prognostic Implications

• Early detection of AL amyloidosis allows for plasma cell-directed chemotherapy (cyclophosphamide, bortezomib, dexamethasone) which can halt amyloid deposition and potentially reverse organ damage if caught early 1, 7
• Delayed diagnosis until symptomatic heart failure develops reduces median survival from 13 months to 4 months 1
• ATTR amyloidosis requires completely different management (TTR stabilizers, gene silencing therapies) than AL amyloidosis, making accurate typing essential for mortality outcomes 2

The presence of smoldering myeloma with new pericardial effusion represents a high-risk scenario that mandates comprehensive evaluation for amyloidosis and plasma cell infiltration, as both significantly impact morbidity, mortality, and treatment strategy. 1, 2, 3