Histological characteristics of sternoclavicular β2-microglobulin amyloidosis and clues for its histogenesis

Background. The pathogenesis of beta 2-microglobulin amyloidosis (A beta(2)m) has yet to be fully elucidated. Methods. We describe the distribution and extent of A beta(2)m deposition and macrophagic infiltration in cartilage, capsule, and synovium of sternoclavicular joints obtained postmortem from 54 patients after 3 to 244 (median 46) months of dialysis. Twenty-four nonuremic patients served as a control group. The diagnosis of amyloidosis (A) rested on a positive Congo Red staining (typical birefringence) and that of A beta(2)m on positive immunostaining of the A deposits with a monoclonal anti-beta 2m antibody. The size of A deposits was measured. Results. A beta(2)m was detected in 32 (59%), and non-beta(2)m amyloid (Anon beta(2)m) was detected in an additional 8 (15%) of the 54 dialyzed patients. A beta(2)m deposits were present in the cartilage of all A beta(2)m (+) patients (100%). They were localized solely in the cartilage in 27% of the cases, either as a thin patchy layer or as a continuous thicker layer (identified as stage I). A beta(2)m was additionally present in the capsule and/or synovium without macrophages in 27% of the cases (identified as stage II). The correlation between the size of cartilaginous deposits and dialysis duration (P = 0.02) as well as with the prevalence (P = 0.03) and size of capsular deposits (P = 0.02) suggests that stage II is a later stage of A deposition. Clusters of macrophages were detected around capsular and synovial amyloid deposits in 46% of the cases (identified as stage III). The longer duration of dialysis in those with stage III as well as the relationship between the size of the A beta(2)m deposits and the prevalence of macrophagic infiltration suggests that stage III is the last stage of A beta(2)m deposition. Marginal bone erosions were observed in 9 out of 12 patients with stage III deposits. Their size was correlated with that of cartilaginous deposits (P = 0.01). Among the 24 control patients, Anon beta(2)m was detected in 12 patients (cartilage 100%, capsule 8%, synovium 30%). Conclusions. The earliest stage of A beta(2)m deposition occurs in the cartilage. A beta(2)m subsequently extends to capsule and synovium. These two first stages do not require macrophage infiltration. Macrophages are eventually recruited around larger synovial or capsular deposits in the final stage. Marginal bone erosions develop in this late stage.