Abstract: TH-PO1108
Diagnostic Challenges in AL Amyloidosis with Low-Level Paraproteinemia
Session Information
- Pathology and Lab Medicine
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
Authors
- Gakhokidze, David, Nephrology Associates of Tidewater LTD, Norfolk, Virginia, United States
- Plasse, Richard A., Nephrology Associates of Tidewater LTD, Norfolk, Virginia, United States
Introduction
AL amyloidosis is a systemic plasma cell disorder caused by extracellular deposition of misfolded immunoglobulin light chains and commonly presents with renal involvement. Diagnosis may be challenging when monoclonal studies demonstrate only subtle abnormalities despite significant organ dysfunction. We present a case of biopsy-confirmed renal AL amyloidosis in a patient with minimal detectable monoclonal gammopathy on initial evaluation.
Case Description
A 69-year-old male presented with one week of progressive bilateral lower extremity edema, severe generalized weakness, and altered mental status. Initial laboratory evaluation demonstrated nephrotic-range albuminuria with urine microalbumin approaching 3 grams and evidence of renal dysfunction. Immunologic workup including autoimmune serologies was unremarkable. Serum free light chain analysis demonstrated a kappa/lambda ratio of 0.3. Serum immunofixation revealed a faint IgG lambda monoclonal band, while urine immunofixation demonstrated a faint lambda light chain band without a significant monoclonal spike on serum protein electrophoresis.
Given unexplained nephrotic-range proteinuria and progressive clinical decline, a native kidney biopsy was performed. Light microscopy demonstrated amorphous eosinophilic deposits with Congo red positivity and apple-green birefringence under polarized light. Immunofluorescence microscopy revealed diffuse 3+ mesangial matrix and arteriolar staining for lambda light chains. Electron microscopy demonstrated randomly arranged nonbranching fibrils measuring approximately 8–12 nm in diameter, consistent with amyloid deposition. Pathologic findings confirmed AL (lambda) amyloidosis involving the kidney.
Discussion
This case highlights the diagnostic difficulty of AL amyloidosis when monoclonal protein studies reveal only faint abnormalities. Small plasma cell clones may produce limited detectable paraprotein despite extensive tissue involvement. Reliance solely on SPEP or subtle immunofixation findings may delay diagnosis and treatment. Kidney biopsy remains essential in patients with otherwise unexplained nephrotic syndrome or progressive renal dysfunction, particularly when clinical suspicion for amyloidosis persists despite equivocal hematologic studies. Early tissue diagnosis is critical to facilitate timely initiation of clone-directed therapy and improve clinical outcomes
Acknowledgment
I thank Dr. Richard Plasse for mentorship and clinical guidance, and the renal pathology department for assistance with histopathologic diagnosis and interpretation.