Localized Amyloidosis of the Urinary Bladder: New Pathological Features Revealed by Mass Spectrometry-Based Proteomics
Oana M Mereuta, Anita D'Souza, Julie A Vrana, Jason D Theis, Patrick S Quint, Angela Dispenzieri, Karen L Grogg, Ahmet Dogan. Mayo Clinic, Rochester, MN; University of Torino, Torino, Italy
Background: Amyloidosis is characterized by extracellular deposition of Congo-red (CR) positive fibrillar protein aggregates and can be systemic or localized. In recent years, mass spectrometry (MS)-based proteomic analysis has allowed accurate typing of the amyloid deposits in clinical biopsy specimens. Localized amyloidosis of the urinary bladder is a rare entity which frequently mimics a malignancy. A detailed biochemical characterization of the amyloidosis in the bladder has not been performed but immunohistochemical studies suggest immunoglobulin as the main constituent. The aim of this study was to establish the biochemical composition and pathological features of bladder amyloidosis by combining laser microdissection (LMD) and MS proteomic analysis.
Design: We analyzed 90 cases of localized bladder amyloidosis diagnosed since 2008. For each case, hematoxylin-eosin and CR sections were examined. The CR positive areas were analyzed using LMD and MS. In 24 cases of immunoglobulin light (AL) or heavy (AH) chain amyloidosis, the presence of clonal plasma cells associated with amyloid deposits was assessed by immunohistochemistry and in situ hybridization for kappa/lambda light chains.
Results: MS analysis identified 38 AL cases (42%) with 30 cases of λ type and 8 cases of κ type; 18 mixed AH/AL cases (20%) with gamma (n=9), delta (n=5), alpha (n=3), mu (2 cases) heavy chains and λ (n=15) or κ (n=3) association; 1 AH case (1%); 29 cases (32%) of senile-type ATTR amyloidosis; 1 case (1%) of secondary AA amyloidosis and 1 case (1%) of semenogelin I (ASemI) amyloidosis. Moreover, we identified a predominant light chain variable region (VL) gene usage of VλI family in 12 cases of λ group and 6 cases of AH/ALλ group. No preferential Vκ gene usage was detected. AL and AH amyloidosis showed a predominant nodular pattern in the mucosa whereas ATTR exhibited a vascular pattern. A monotypic light chain expression pattern was evidenced in 8 cases (5 λ and 3 κ). These results suggest a local production of the light chain proteins.
Conclusions: The etiology of localized bladder amyloidosis is diverse and in addition to AL amyloidosis includes AH/AL, ATTR, AA and ASemI amyloidosis. A subset of AL/AH amyloidosis contains clonal plasma cells suggesting that they are caused by localized plasma cell neoplasms. Therefore, MS proteomic analysis allows reliable amyloid typing and important management decisions in clinical practice.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 176, Monday Afternoon