Abstract: FR-PO190
Clinicopathologic and Proteomic Characteristics of Intratubular Cytoplasmic AL-Amyloidosis
Session Information
- Onconephrology: Clinical and Research Advances - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Javaugue, Vincent, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
- Best Rocha, Alejandro, Arkana Laboratories, Little Rock, Arkansas, United States
- Said, Samar M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Santoriello, Dominick, Columbia University, New York, New York, United States
- Hou, Jean, Cedars-Sinai Medical Center, Los Angeles, California, United States
- Dasari, Surendra, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Theis, Jason David, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Vrana, Julie A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Batal, Ibrahim, Columbia University, New York, New York, United States
- Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
- Markowitz, Glen S., Columbia University, New York, New York, United States
- D'Agati, Vivette D., Columbia University, New York, New York, United States
- Mcphail, Ellen Darcy, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Leung, Nelson, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Nasr, Samih H., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
AL-amyloid deposits have been described in all compartments of the kidney. However, intratubular cytoplasmic AL amyloidosis (ITC-AL) is exceedingly rare and only described in few case reports.
Methods
We retrospectively reviewed the pathology archives at Mayo Clinic, Columbia University, Arkana Laboratories and Cedars-Sinai Medical Center from 2006-2021 for ITC-AL.
Results
Twenty-one patients (71% female, 58% Caucasian, median age 65 years) were included (0.003% of renal amyloidosis). Nineteen presented with AKI and 2 with CKD stage 3, without evidence of Fanconi syndrome. By light microscopy, the intracytoplasmic amyloid inclusions were black on silver stain, PAS-negative and trichrome-blue. They were identified in both proximal and distal tubular cells (n=12), in proximal tubular cells alone (n=5) or distal tubular cells alone (n=4). Ultrastructurally, these inclusions appeared membrane-bound consistent with intralysosomal localization. Concurrent cast nephropathy was present in 18 cases (amyloidogenic in 15). By immunofluorescence, amyloid deposits stained for lambda (n=18) or kappa (n=3). No patient had glomerular or interstitial amyloid deposits while 2 had vessels involvement. Extrarenal amyloid deposits were found in 3 cases. Proteomic analysis of kidney amyloid deposits identified a single light chain variable gene segment in all tested cases (IGLV1-47 in 2, IGLV1-44 in 1 and IGLV3-21 in 1). None had the glomerulopathic IGVL6-57. The underlying hematologic condition was multiple myeloma in 13/13 cases (symptomatic in 11). Patients were treated with bortezomib- (n=11) or lenalidomide-based (n=2) regimens followed by autologous stem cell transplant in 2. After a median follow-up of 14 months (range 1-51), 1 died one month after diagnosis, 4 progressed to ESKD (3 of them died) and 6 had partial recovery of kidney function.
Conclusion
ITC-AL occurs mostly concurrent with cast nephropathy and thus presents with AKI. Some cases are associated with extrarenal involvement by amyloidosis. Whether the amyloid fibrils are formed within the cells from reabsorbed light chains or result from phagocytosis of already formed intratubular luminal fibrils remains to be determined.