Amyloidosis of the Liver: Mass Spectrometry-Based Proteomic Analysis Reveals Diverse Etiology Associated with Distinct Histological Features
Julie A Vrana, Jason D Theis, Karen L Grogg, Tsung-Teh Wu, Vishal S Chandan, Ahmet Dogan. Mayo Clinic, Rochester, MN
Background: Amyloidosis is a protein folding disorder characterized by extracellular accumulation of Congo-red (CR) positive fibrillar deposits. Despite this common histological feature, 28 different proteins have been shown to cause either localized or systemic amyloidosis. Systemic amyloidosis frequently involves the liver, and both the initial diagnosis and typing of amyloid deposits may be challenging. In recent years, mass spectrometry (MS) proteomic analysis has become the gold standard for typing amyloidosis but so far it has not been systemically applied to liver specimens. The aim of this study was to define the pathological features of amyloidosis involving the liver using MS proteomic analysis.
Design: 92 cases of amyloidosis involving the liver were analyzed between 2009-2011. For each case, routine histological sections and CR stains were reviewed, and microdissected fragments of amyloid deposits were analyzed by MS proteomic analysis.
Results: In each case amyloid deposition was confirmed by CR staining. Amyloid deposits had several distinct histological patterns. The most common pattern was peri-sinusoidal (65/92), followed by predominantly portal/globular (22/92), portal/nodular (4/92) and predominantly vascular involvement (1/92). MS proteomic analysis showed that the amyloid deposits were AL-type in 64 cases (30 AL-kappa, 34 AL-lambda), ALect2 in 21 cases, AApoA1 in 4 cases, and ALys, AA and ATTR in one case each. Interestingly, distinct morphological patterns correlated with specific amyloid types. All AL and AA cases had predominantly peri-sinusoidal pattern of involvement, ALect2 and ALys cases had a distinct portal/globular pattern, AAPOA1 cases had a portal/nodular pattern, and the single case of ATTR showed a predominantly vascular pattern.
Conclusions: 1. The etiology of systemic amyloidosis involving the liver is diverse and, in addition to AL and AA amyloidosis include ALect2, AApoA1, ALys and ATTR amyloidosis.
2. ALect2 amyloidosis, recently described as a frequent cause of renal amyloidosis in patients of Hispanic origin, also frequently involves the liver with characteristic portal globular pattern.
3. The histological pattern of liver involvement by amyloidosis provides strong clues with regards to the etiology of the deposits.
4. Given the diversity of amyloid types that could involve the liver, and the differences in management strategies for different types of amyloidosis, typing of amyloid deposits is essential. MS proteomic analysis provides a powerful and comprehensive tool for this purpose.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 244, Wednesday Morning