Hematology Oncology · Year 2 · from Hematology Oncology
Case 2: AL Amyloidosis with Cardiac Involvement
Patient Presentation
Demographics: 62-year-old female
Chief Complaint: Progressive shortness of breath and leg swelling
History of Present Illness: The patient has had progressive dyspnea on exertion over 6 months, now dyspneic at rest. She has developed bilateral leg swelling and reports feeling lightheaded when standing. She also notes easy bruising around her eyes and an enlarged tongue that makes eating difficult.
Physical Examination:
- Blood pressure: 95/65 mmHg (orthostatic hypotension present)
- Heart rate: 92 bpm
- JVP: Elevated to 14 cm
- Periorbital ecchymoses ("raccoon eyes")
- Macroglossia with lateral tongue scalloping
- Cardiac: Distant heart sounds, S4 gallop
- Lungs: Bibasilar crackles
- Abdomen: Hepatomegaly
- Extremities: 3+ pitting edema to thighs
Workup and Results
Laboratory Studies:
- BNP: 2,450 pg/mL (markedly elevated)
- Troponin T: 0.08 ng/mL (elevated)
- Creatinine: 1.4 mg/dL
- Albumin: 2.8 g/dL
- 24-hour urine protein: 4.2 g
Serum Studies:
- SPEP: Small M-spike (0.4 g/dL, IgG lambda)
- Free light chains: Lambda 185 mg/L, Kappa 8 mg/L
Echocardiogram:
- Increased wall thickness (1.6 cm)
- "Sparkling" myocardium
- Diastolic dysfunction, restrictive filling
- EF 45%
Cardiac MRI:
- Diffuse late gadolinium enhancement
- Pattern consistent with cardiac amyloidosis
Abdominal Fat Pad Biopsy:
- Congo red positive with apple-green birefringence
- Mass spectrometry: AL (lambda) amyloid
Bone Marrow Biopsy:
- 12% clonal lambda-restricted plasma cells
Clinical Image
Echocardiogram demonstrating characteristic findings of cardiac amyloidosis: increased biventricular wall thickness with "sparkling" granular appearance of the myocardium and small pericardial effusion.
Diagnosis
AL (Light Chain) Amyloidosis with Cardiac Involvement
Features:
- Lambda light chain excess
- Congo red positive amyloid deposits
- Multi-organ involvement: heart, kidney (proteinuria), soft tissue (macroglossia, periorbital purpura)
- Advanced cardiac staging
Discussion
This case illustrates AL amyloidosis:
- Light Chain Deposition: The lecture describes AL amyloidosis as deposition of misfolded immunoglobulin light chains in tissues. Unlike myeloma, the plasma cell burden is often small (<10%), but the secreted light chains cause organ damage.
- Congo Red Staining: The lecture identifies Congo red staining with apple-green birefringence under polarized light as the diagnostic test for amyloid.
- Cardiac Involvement = Prognosis: The lecture emphasizes that cardiac involvement is the most important prognostic factor in AL amyloidosis. Elevated cardiac biomarkers (troponin, BNP) indicate advanced cardiac staging.
- Classic Clinical Features: Macroglossia and periorbital purpura are classic but not universal findings. The purpura results from amyloid infiltration of blood vessel walls.
Treatment Plan
- Staging and Risk Assessment:
- Mayo cardiac staging based on troponin and NT-proBNP
- High-risk cardiac involvement present
- Treatment Options:
- Daratumumab-based regimen (Dara-VCd: daratumumab, bortezomib, cyclophosphamide, dexamethasone)
- Autologous transplant if eligible (limited by cardiac involvement)
- Supportive Care:
- Diuretics for volume overload (careful - may worsen orthostatic hypotension)
- Midodrine for orthostatic hypotension
- Avoid digoxin (binds to amyloid fibrils)
- Compression stockings
- Monitoring:
- Serial free light chains (goal: hematologic response)
- Cardiac biomarkers
- Organ response assessment
Teaching Points
- AL amyloidosis involves light chain deposition; plasma cell burden is often small
- Congo red staining shows apple-green birefringence under polarized light
- Cardiac involvement is the most important prognostic factor
- Macroglossia and periorbital purpura are classic findings
- Avoid digoxin (binds amyloid fibrils)