Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells

Abstract

ObjectivesTo describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM).MethodsSynovial biopsies from affected joints of two patients with MM and amyloid arthropathy were examined with light and electron microscopy, and immunohistochemically for expression of CD3, CD8, CD20, CD38, CD68, Ki-67 and vWF. Results were compared to values from osteoarthritis (OA, n = 26), rheumatoid arthritis (RA, n = 24) and normal (n = 15) synovial membranes.ResultsThere was no or only mild lining hyperplasia. Vascular density was not elevated, and there were few Ki-67+ proliferating cells in the stroma. The Krenn synovitis score classified one specimen as “low-grade” and one as “high-grade” synovitis. CD68+ and CD3+ cells were the predominant mononuclear inflammatory cells, whereas CD20+ and CD38+ cells were absent from both synovial membrane and synovial fluid sediment. Electron microscopy demonstrated amyloid phagocytosis by synovial macrophages. In hierarchical clustering the two amyloid arthropathy specimens were more closely related to OA than to RA or normal synovium.ConclusionsThis first detailed immunohistological analysis of MM-associated amyloid arthropathy suggests that it is a chronic synovitis that evolves despite the loss of humoral immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial macrophages likely triggers and perpetuates local disease.

Multiple myeloma characterized by synovial fibrinoid necrosis: a case report

“…In relatively mild synovitis, the majority of the mononuclear inflammatory cells were identified as cluster of differentiation (CD) 68 p macrophages. 9 This finding is not consistent with the results of our patient's synovial biopsy; thus, we infer that there are still important and unknown factors in the pathogenesis of MAA. Compared with general MAA patients, our patient had more severe symptoms and lower concentrations of IL-6.…”

Joint Pain and Arthritis as First Clinical Manifestation of Systemic Amyloidosis and Multiple Myeloma: Case Report and Brief Literature Review

“…About 1/3 of patients are misdiagnosed as RA [ 8 ], even though the two conditions are pathogenetically and clinically different [ 8 , 9 ].…”

“…Unlike RA, AA is a chronic synovitis related to the phagocytosis of fibrillar amyloid by macrophages; the activation of the macrophage leads to the activation of pre-(IL)-1β to IL-1β and, as a consequence, to the activation of pro-inflammatory cascades in other cells. Thus, AA seems to be mediated by an undue activation of the innate immune system rather than by a lymphocyte-mediated mechanism [ 9 ].…”

Severe hand pain as an extracardiac manifestation of transthyretin amyloidosis

“…The synovial biopsy of involved joints shows abundance of macrophages. The paucity of plasma cells explains the role of local innate immune cells in the progression of joint disease 12. TTR can activate glycation end-product receptors and stimulate nuclear translocation of nuclear factor-κB, leading to cell death in cultured chondrocytes 13–17…”