Renal Amyloidosis: Origin and Pathology of 445 Recent Cases from a Single Center
Samar M Said, Sanjeev Sethi, Lynn D Cornell, Mary E Fidler, Loren Herrera Hernandez, Julie A Vrana, Jason D Theis, Ahmet Dogan, Samih H Nasr. Mayo Clinic, Rochester, MN
Background: Amyloidosis is a rare disorder, characterized by extracellular accumulation of Congo-red-positive fibrillar deposits. The kidney is the most commonly affected organ by amyloidosis. The two most common types of renal amyloidosis are primary amyloidosis and secondary (AA) amyloidosis. Recently, several other types of amyloidosis have been recognized largely due to the introduction of mass spectrometry (MS) for amyloid typing.
Design: We reviewed the type and pathology of renal amyloidosis in all 445 cases diagnosed by renal biopsy from 2007-2011 at our pathology laboratory. Congo red stain was positive in all cases. Renal biopsies were evaluated by light microscopy, immunofluorescence (IF), and electron microscopy. The type of amyloid was determined by IF on frozen tissue, IF on pronase-digested paraffin tissue, immunohistochemistry, MS, and/or genetic testing.
Results: The type of amyloid was primary in 378 patients (84.9%), AA in 33 (7.4%), leukocyte chemotactic 2-associated amyloid (ALect2) in 13 (2.9%), fibrinogen A (AFib) in 5 (1.2%), Apolipoprotein in 3 (0.7%)(AApoAI in 1, AApoAII in 1, and AApoAIV in 1), combined AA and AL-AH in 1 (0.2%) and unclassified in 11 (2.4%)(mainly due to the lack of adequate tissue for IF and/or MS). The subtype of primary amyloidosis was AL in 357 of the 378 patients (94.4%; lambda (λ) in 81% and kappa (κ) in 19%), AL-AH in 15 (4%; IgGλ in 7, IgGκ in 2, IgAκ in 3, IgAλ in 1, IgMκ in 1, IgMλ in 1) and AH in 6 (1.6%, IgG in 5 and IgA in 1). Overall, MS was needed to determine the type of amyloid in 65 cases (15%). The mean age at diagnosis for all 445 patients was 63 yrs (63 for primary amyloidosis, 52 for AA, 66 for ALect2, and 56 for AFib), with a female to male ratio of 1.6. Amyloidosis involved glomeruli in 97% of cases (mesangium in 97% and basement membranes in 86%), vessels in 84%, interstitium in 58% and tubular basement membranes in 7%. ALect2 and AFib had a distinctive pattern of involvement: ALect2 was characterized by diffuse interstitial deposition, while AFib showed massive obliterative glomerular involvement.
Conclusions: With the advent of MS for amyloid typing, the type of renal amyloidosis can be determined in > 97% of cases. In our experience, primary amyloidosis accounts for 85% of cases. AL-AH (most frequently IgGλ) or AH (most commonly IgG) comprise 6% of cases of primary amyloidosis. AA, the distant second most common type of renal amyloidosis, is only 3-times more frequent than ALect2 and 6-times more than AFib. ALect2 should be suspected if there is extensive interstitial involvement and AFib if there is massive obliterative glomerular involvement.
Category: Kidney (does not include tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 248, Monday Morning