Synovial Biopsy, Synovium, Synovial Fluid & Arthrocentesis

Synovium Amyloidosis Photo/Slide Viewer


Amyloidosis is the disease caused by deposition of a material that is fibrillar by electron microscopy and stained with Congo red by light microscopy. Symptoms vary with the sites infiltrated and may include nephrosis, heart failure, muscle infiltration, skin lesions with easy bleeding, malabsorption and neuropathy.

Arthropathy due to Amyloidosis is unusual but had been reported in causes including multiple myeloma, “primary Amyloidosis” and in Waldenstrom’s macroglobulinemia (1-3). Joint difficulties from amyloid deposition have not been described after chronic inflammatory conditions such as tuberculosis and rheumatoid arthritis. Patients with arthropathy have generally had widespread Amyloidosis.

Amyloidosis often produces joint stiffness, synovial thickening, subcutaneous nodules and erosive bone lesions that somewhat mimic rheumatoid arthritis. Heat and erythema are not seen and most joint effusions have been “non-inflammatory.” Morning stiffness is not typical. Other musculoskeletal problems include bone lesions and carpal tunnel syndrome. Subcutaneous amyloid nodules may mimic those of RA.


Firm pink nodules of amyloid may be seen and palpated through the synovium (3). Another synovium at post mortem was diffusely thickened and pale yellow (1).


There is neither acute nor chronic inflammation in amyloid synovial. Amyloid can be seen on the surface, mixed with the lining cells, in large tumefactions (3) and in only small amounts in vessel walls. The amyloid appears pink on H and E stains and red with Congo red. The Congo red stained areas show a characteristic apple green birefringence with polarized light. Very few cases have had histologic study.


Amyloid in most tissues consists of 100A diameter fibrils. Such fibrils have been documented in synovial fluid, on the synovial surface, adjacent to synovial cells rich in dilated endoplasmic reticulum and between endothelium and pericytes. Some vessels had multilaminated basement membranes (1). Phagocytic lining cells were not common.


























Free floating masses of amyloid have been seen and account for some cloudiness of effusions. Paraffin sections of such masses can be stained with Congo red and shown to be amyloid (5). Wet smears with amyloid masses can also be stained with Congo red.


Diagnosis of amyloidosis can be established on synovial membrane and fluid as above so readily that this may be the easiest and safest technique to diagnose systemic amyloid when joints are involved. Since synovial vessels are rarely infiltrated this seems safer than other biopsies.

Why amyloid so rarely deposits in joints is unclear. The electron micrographs with amyloid fibrils immediately adjacent to type B lining cells and Cohen et al’s observation that amyloid can be synthesized by cells without intact blood supply suggests that it may originate in synovial cells. The fact that amyloid fibril protein is reportedly very similar to the amino terminal fragment of the variable portion of an immunoglobulin light chain suggests a relation to disorders of immune mechanisms. Plasma cells and inflammatory cells, however, have been strikingly absent from joint lesions. Joint involvement seems to become symptomatic due to the sheer mass of abnormal material. Masses of amyloid in the synovial fluid may contribute to some of the stiffness noted.

Note that amyloidosis can indirectly involve the joint by producing neuropathy leading to a Charcot joint (8) or bone disease.

Light microscopic evidence of amyloid has been reported in synovium or joint capsule rheumatoid arthritis (6), gout, aseptic necrosis, osteoarthritis (7), and even in normal autopsied joints in the elderly (9), but none of this has been studied in any depth. Deposits appear to be scanty and easily distinguished from the massive material seen in amyloid arthropathy. Much of this has been described as resistant to permanganate as is “senile amyloid.”



  1. Schumacher HR. Multiple myeloma with synovial amyloid deposition. Rheum Phys Med 11:349-353, 1972.
  2. Goldberg A, Brodsky I and McCarty DJ. Multiple myeloma with para-amyloidosis presenting as rheumatoid disease. Am J Med 37:653, 1964.
  3. Wiernik PH. Amyloid joint disease. Medicine 51:465-479, 1972.
  4. Cohen A, Gross E and Shirahama T. Light and electron microscopic autoradiographic demonstration of local amyloid formation in spleen explants. Am J Path 47:1079, 1965.
  5. Gordon DA, Pruzarski W, Ogryzlo MA. Synovial fluid examination for the diagnosis of amyloidosis. Ann Rheum Dis 32:428-430, 1973.
  6. Laine V, Vainio K and Ritama VV. Occurrence of amyloid in rheumatoid arthritis. Acta Rheum Scand 1:43-46, 1955.
  7. Sorensen KH, Christensen HE. Local amyloid formation in the hip joint capsule in osteoarthritis. Acta Orthop Scand 44:460-466, 1973.
  8. Peitzman SJ, Miller JL, Ortega L, Schumacher HR, Fernandez PE. Charcot arthropathy secondary to amyloid neuropathy. JAMA 235:1345-1347, 1976.
  9. Goffin YA, Thoua Y and Potvliege PR. Microdeposition of amyloid in the joints. Ann Rheum DIs 40:27-33, 1981.

More References Related to Synovium Amyloidosis

Gisserot O, Landais C, Cremades S, et al. Amyloid arthropathy and Waldenstrom macroglobulinemia. Joint Bone Spine, 73:456-458; 2006.

Bukhari M. Freemont AJ, Noble J and Jayson MIV. Erosive amyloidosis of the wrist and knee associated with oligoclonal bands. British J Rheumatol 36:494-497, 1997.

Maury CPJ. Beta2-microglobulin amyloidosis. A systemic amyloid disease affecting primarily synovium and bone in long-term dialysis patients. Rheumatol Int 10:1-8, 1990.

Munoz-Gomez J, Gomez-Perez R, Sole-Arques M and Llopart-Buisan E. Synovial fluid examination for the diagnosis of synovial amyloidosis in patients with chronic renal failure undergoing haemodialysis. Annals of the Rheumatic Diseases, 46:324-326, 1987.

Stein K, Storkel S, Linke RP and Goebel HH. Chemical heterogeneity of amyloid in the carpal tunnel syndrome. Virchows Arch A, 412:37-45, 1987.

Noel LH, Voisin MC, Atienze CI, Zingraff J, Bardin T, et al. Aspects anatomo-pathologiques des amyloses chez les hemodialyses. 8th Gambro Symposium, January, 51-55,1987.

Ritz E, Bommer J, Hansch M and Rauterberg. Beta2-microglobulin (B2m)-derived amyloid - unsolved problems and uncertainties about dialytic strategies. 8th Gambro Symposium, 107-112, January, 1987.

Ladefoged C. Amyloid deposits in the knee joint at autopsy. Annals of the Rheumatic Diseases, 45:668-672, 1986.

Munoz-Gomez J, Bergada-Barado E, Gomez-Perez R et al. Amyloid arthropathy in patients undergoing periodical haemodialysis for chronic renal failure: a new complication. Annals of the Rheumatic Diseases, 44:729-733, 1985.

Mitrovic DR, Stankovic A, Quintero M and Ryckewaert A. Amyloid deposits in human knee and hip joints. Rheumatol Int, 5:83-89, 1985.

Rowe IF. Editorial: Amyloid arthropathy. Annals of the Rheumatic Diseases, 44: 727-728, 1985.

Pras M, Itzchaki M, Prelli F, Dollber and Frangione B. Amyloid arthropathy: characterization of the amyloid protein. Clinical and Experimental Rheumatology, 3:327-331, 1985.

Mitrovic DR et al. Amyloid deposits in human knee and hip joints. Rheumatology International 5:83-89, 1985.

Lovy M, Anderson P, Steigerwald J. Ankylosing spondylitis, selective IgA deficiency and systemic amyloidosis with intrasynovial amyloid deposition. J Rheum, 10:337-341, 1983.

Ladefoged C. Amylod in osteoarthritic hip joints: deposits in relation to chondromatosis, pyrophosphate, and inflammatory cell infiltrate in the synovial membrane and fibrous capsule. Annals of the Rheumatic Diseases, 42:659-664, 1983.

Horwitz HM, DiBeneditto JD, Allegra SR and Baumann HM. Scleroderma, amyloidosis, and extensor tendon rupture. Arthritis and Rheumatism, 25:1141-1143, 1982.

Ryan LM, Liang G and Kozin F. Amyloid arthropathy: possible association with chondrocalcinosis. J Rheumatol 9:273-278, 1982.

Egan MS, Goldenberg DL, Cohen AS and Segal D. The association of amyloid deposits and osteoarthritis. Arthritis and Rheumatism 25:204-208, 1982.

Fam AG, Lewis AJ and Cowan DH. Multiple myeloma and amyloid bone lesions complicating rheumatoid arthritis. J Rheumatol 8:5:845-850, 1981.

Friedman R, Agus B and Ames E. Amyloid arthropathy in a patient with psoriasis and amyloidosis. Arthritis and Rheumatism, 24:1320-1323, 1981.

Hickling P, Wildins M, Newman GR et al. A study of amyloid arthropathy in multiple myeloma. Quarterly J of Med, New Series L, 50:417-422, Autumn 1981.

Hajzok O, Tomik F & Hajzokva M. Amyloidosis in rheumatoid arthritis. A study of 48 biologically confirmed cases. Z Rheumatol 35:356-362; 1976.

Peitzman SJ, Miller JL, Ortega L, Schumacher HR & Fernandez PC. Charcot arthropathy secondary to amyloid neuropathy. JAMA, 235:1345-1347; 1976.

Cohen AS & Canoso JJ. Rheumatological aspects of amyloid disease. Clinics in Rheumatoc Diseases 1:149-161; 1975.

Gordon DA, Pruzanski W, Ogryzlo MA & Little HA. Amyloid arthritis simulating rheumatoid disease in five patients with multiple myeloma. Am J Med, 55:142-154; 1973.

Schumacher HR. Multiple myeloma with snyovial amyloid deposition. Rheum phys Med. 11:349-353; 1972.

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