The Reliability and Accuracy of Immuno-Gold Electron Microscopy for Subtyping Amyloid; Correlation with Laboratory Studies and Clinical Setting.
Dehua Wang, John Lee, Pamela T Soo Hoo, Carl J O'Hara. Boston University Medical Center, Amyloid Treatment and Research Center, MA
Background: Immuno-gold electron microscopy (EM) has shown promise as an additional modality for amyloid typing. The sensitivity and specificity of this modality has not been fully assessed due to the limited number of cases studied. This study analyzed 64 patients with systemic amyloidosis subtyped by immuno-gold-EM and assessed how often the subtype was corroborated by ancillary studies and clinical setting.
Design: Immuno-gold-EM was performed on 40 fat aspirates, 16 heart biopsies, 2 colon biopsies, 1 each of renal, gastric, duodenum, liver, tongue and lung using antibodies to amyloid A, AL-kappa, AL-lambda and TTR. The subtypes were then compared to the available data for routine IHC, isoelectric focusing for TTR mutations and clinical data including patients' history, immunoglobulin studies ( serum protein electrophoresis, immunofixation, free light chain analysis), bone marrow plasma cell clonality and volume as well as the spectrum of organ involvement. Two-tailed p values<0.05 was considered significant in McNemar Χ2 test for sensitivity and Fisher's exact test for the 2x2 table.
Results: 84.6% (54/64) of cases were successfully subtyped by immuno-gold-EM. There were 19 TTR, 23 AL-λ, 4 AL-κ, 4 AA and 4 mixed type with 2 cases of TTR coexisting with AL-κ, 1 case of TTR coexisting with AL-λ and 1 case of AA coexisting with AL-κ. The amyloid was subtyped in 32 of 40 cases (80.0%) of fat aspirates and 22 of 24 organ biopsies (91.7%) (p=0.297). In 23 cases in which initial amyloid typing was attempted by routine immunohistochemistry (IHC), 91.3% (21/23) were successfully subtyped by immuno-gold whereas only 8/23 cases (34.8% ) could be subtyped by routine IHC alone (p=0.009). when compared to the laboratory data and clinical presentation, there was a very good corroboration with the specific amyloid subtype
Conclusions: 1. Immuno-gold-EM subtyping of amyloid is accurate and reliable.
2. Immuno-gold-EM can be successfully applied to fat aspirates as well as organ biopsies.
3. In the majority of cases evaluated, ancillary studies and the clinical setting supported the amyloid subtype determined by immuno-gold-EM.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 284, Wednesday Morning