Abstract: SA-PO841
A Rare Case of Waldenstrom Macroglobulinemia-Associated AHL Amyloidosis and Nephrotic Syndrome
Session Information
- C3G, TMA, MGRS, Amyloidosis, and More
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Smith, Alexander M., Ochsner Medical Center, New Orleans, Louisiana, United States
- Da Silva, William, Ochsner Medical Center, New Orleans, Louisiana, United States
- Kanduri, Swetha Rani, Ochsner Medical Center, New Orleans, Louisiana, United States
- Zarm, Ayaa M., Ochsner Medical Center, New Orleans, Louisiana, United States
- Velez, Juan Carlos Q., Ochsner Medical Center, New Orleans, Louisiana, United States
- Yang, Chien-Wen, Ochsner Medical Center, New Orleans, Louisiana, United States
Group or Team Name
- Ochsner Group.
Introduction
AHL amyloidosis (combined heavy and light chain) is a rare subtype of amyloidosis, accounting for 4.2% of the Ig-related amyloidosis. Waldenstrom macroglobulinemia (WM), is linked to 5–7% of the Ig-related amyloidosis. Herein, we present a very rare case of WM-associated AHL amyloidosis who presented with normal serum kappa/lambda free light chain (FLC) ratio and positive Congo-red staining for amyloid on renal biopsy and confirmed by mass spectrometry.
Case Description
A 65-year-old woman presented with a 2-month history of bilateral lower legs swelling. Her medical history was pertinent for a remote stage III colon cancer. She had been diagnosed with WM 2 years prior and was managed with rituximab and bendamustine, and switched to acalabrutinib, a BTK inhibitor. On examination, she was hypotensive (86/56 mmHg), had marked bilateral 3+ pitting edema. Laboratory work up revealed a serum creatinine 0.7 mg/dL, albumin 1.8 g/dL, and urine protein-to-creatinine ratio 10 g/g. Serum protein electrophoresis (SPEP) showed a paraprotein peak near gamma. IgM level was high (1590 mg/dL) and kappa/lambda FLC ratio was normal (0.83/1.11). Cryoglobulin, anti-PLA2R, RPR, C3/C4 levels were normal. Renal biopsy revealed 25% glomerulosclerosis, 10-20% interstitial fibrosis and tubular atrophy, with immunofluorescence positive for IgM and lambda light chain restriction in glomeruli, and positive Congo-red stain. Mass spectrometry confirmed AHL-type amyloidosis. Bone-marrow biopsy showed 5-10% involvement by lambda light-chain restricted plasma cells and Congo-red stain positive. Bortezomib-based therapy was contraindicated due to severe neuropathy from prior oxaliplatin exposure, so zanubrutinib, a BTK inhibitor, was started based on efficacy consideration. She remains on this regimen and is being evaluated for bone marrow transplantation.
Discussion
This case exemplifies a very rare presentation of AHL amyloidosis in a patient with previously diagnosed WM. Interestingly, despite significant light chain deposition in renal pathology, serum lambda chain levels were normal. Hence, confirmatory tests including Congo-red staining on tissue biopsy and mass spectrometry were required for diagnosis. Renal prognosis is closely related to hematological responses.