Synovial Biopsy, Synovium, Synovial Fluid & Arthrocentesis
CALCIUM PYROPHOSPHATE DIHYDRATE (CPPD) DEPOSITION CPPD crystal deposition is believed to occur when excessive calcium or pyrophosphate ions accumulate. Factors that influence deposition of these include cartilage matrix vesicles, various ecto-enzyme activities, and the anion transporter ANK. The host response to these crystals leads to a variety of clinical and pathologic presentations generally restricted to the joints.
Joints with CPPD crystals can show white frosty appearing deposits coating cartilage and encrusting synovial villi when seen at arthroscopy or at surgery in advanced cases (Fig.1)
B. Synovium and Periarticular Tissues
CPPD crystal deposition has been localized to cartilage and menisci but also synovium joint capsules, tendons, and in intraarticular ligaments (3,13). Of these, more common sites include the synovium of the shoulder and knee and the cruciate ligaments in the knee.
In synovium, CPPD crystals are often seen as birefringent tophus-like aggregates under the lining (Fig. 5). Crystals are not dissolved out by formalin but can be lost in decalcified specimens. Crystal sites are hematoxyphilic. Sites of chrondrometaplasia are often seen adjacent to deposits (Fig. 6) suggesting that some deposits are formed by these transformed cells. Others CPPD may be sequestered from joint fluid. Osteochrondromatosis has been associated with CPPD deposition (14). Early in an acute attack of pseudogout, the edematous synovium is infiltrated with polymorphonuclear leukocytes. . This is followed by mononuclear infiltration and fibroblastic proliferation. Synovial proliferation and infiltration with chronic inflammatory cells in chronically symptomatic joints may resemble rheumatoid synovitis (13). In patients with pseudo-osteoarthritis undergoing knee replacement, synovial deposits tend to be focal and localized to avascular areas (47). Surgical samples excised from involved ligaments have shown chondrometaplasia and CPPD crystals.
Dense foamy CPPD crystals or the holes from which they have been dislodged can be seen in vacuoles of synovial macrophages, PMN, synovial fibroblasts or lying in the matrix (Fig. 7) (3,13,15). A dramatic finding in synovium is that what appear to be tiny CPPD crystals can be seen lined up on or along collagen fibers (16) suggesting their role in crystal deposition or growth (Fig. 8).
1. Reginato AJ, Schumacher HR, Martinez VA. The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study. Arthritis Rheum 1974;17:977-992.
2. Ryan L., McCarty DJ. Calcium pyrophosphate crystal deposition disease; pseudogout; articular chondrocalcinosis. In: McCarty DJ, ed. Arthritis and Allied Conditions, 11th ed. Philadelphia: Lea & Febiger, 1989:1711-1736.
3. Schumacher HR. Pathology of crystal deposition diseases. Rheum Dis Clin North Am 1988;14:269-288.
4. Mitrovic D. Pathology of articular deposition of calcium salts and their relation to osteoarthritis. Ann Rheum Dis 1983;42(suppl):19-26.
5. Bjelle A. Cartilage matrix in hereditary pyrophosphate arthropathy. J Rheumatol 1981;8:959-964.
6. Ishikawa K, Masuda I, Ohira T, et al. A histopathological study of calcium pyrophosphate dihydrate crystal-deposition disease. J Bone Joint Surg 1989;71A:875-866.
7. Ohira T, Ishikawa K, Masuda I, et al. Histologic localization of lipid in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 1988;31:1957-1062.
8. Masuda I, Ishikawa K, Usuku G. et al. A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease. Clin Orthoped 1991;263:272-287.
9. Chen F, Kerner MB, Dorfman HD, et al. The distribution of S-100 protein in articular cartilage from osteoarthritic joints. J Rheumatol 1990;17:1676-1681
10. Ishikawa K, Ueba Y, Isobe T, et al. Interaction of polymorphonuclear leukocytes with calcium pyrophosphate dihydrate crystals deposited in chondrocalcinosis cartilage. Rheumatol Int 1987;7:217-221.
11. Ali SY, Griffiths S, Bayliss MT, et al. Ultrastructural studies of pyrophosphate crystal deposition in articular cartilage. Ann Rheum Dis 1983;42(suppl):97-98.
12. Boivin G, Lagier R. An ultrastructural study of articular chondrocalcinosis in cases of knee osteoarthritis. Virchows Arch 1983;400:13-29 (abstr).
13. Schumacher HR. The synovitis of pseudogout: electron microscopic observations. Arthritis Rheum 1968;11:4226-435.
14. Wise CM, Wheeler GE, Irby MR, Schumacher HR. Synovial osteochondromatosis and pseudogout. J Rheumatol 1984;11:229-232.
15. Schumacher HR. Ultrastructural findings in chondrocalcinosis and pseudogout. Arthritis Rheum 1976;19:413-415.
16. Beutler A, Rothfuss S, Clayburne G., et al. Calcium pyrophosphate dihydrate crystal deposition in synovium. Arthritis Rheum 1993;36:704-715.
17. Schumacher HR, Bonner H, Thompson JJ et al. Tumor-like soft tissue swelling of the distal phalanx due to calcium pyrophosphate dihydrate crystal deposition. Arthritis Rheum 1984;27:1428-1432.
18. Egan MS, Goldenberg DL, Cohen AS, et al. The association of amyloid deposits and osteoarthritis. Arthritis Rheum 1982;25:204-208.
19. Dijkgraaf LC, Liem RS, de Bont GM, et al. Calcium pyrophosphate dihydrate crystal deposition disease: a review of the literature and a light and electron microscopic study of a case of the temporomandibular joint with numerous intracellular crystals in chondrocytes. Osteoarthritis Cartilage 1995;3:35-45.
20. Li-Yu J, Schumacher HR, Gratwick G. Invasive tophaceous pseudogout in the temporomandibular joint: Misdiagnosis as a tumor. J Clin Rheumatol 2000;6:272-277.
21. Gordon GV, Villanvera T, Schumacher HR, Gohel V. Autopsy study correlating degree of osteoarthritis, synovitis and evidence of articular calcification. J Rheumatol 1984;11:681-686.
22. Doyle DV. Tissue calcification and inflammation in osteoarthritis. J Pathol 1982;136:199-216.
23. Derfus BA, Kurian JB, Butler JJ. The high prevalence of pathologic calcium crystals in preoperative knees. J Rheumatol2002;29:570-574.
24. Gibilisco P A, Schumacher HR, Jr., Hollander JL, Soper KA. Synovial fluid crystals in osteoarthritis. Arthritis Rheum 1985;511-515.
25. Swan A, Chapman B, Heap P, Seward H, Dieppe P. Submicroscopic crystals in osteoarthritic synovial fluids. Ann Rheum Dis 1994;53:467-470.
26. Halverson PB, McCarty DJ. Patterns of radiographic abnormalities associated with basic calcium phosphate and calcium pyrophosphate dihydrate crystal deposition in the knee. Ann Rheum Dis 1986;45:603-605.
27. Resnick D. Calcium hydroxyapatite crystal deposition disease. In: Resnick D, editor. Diagnosis of bone and joint disorders. 4th ed. Philadelphia: WB Saunders; 2002. p. 1619-1657
28. Gatter RA, McCarty DJ. Pathological tissue calcification in man. Arch Pathol 1967;84:346-353.
29. Reginato AJ, Schumacher HR. Synovial calcification in a patient with collagen-vascular disease: Light and electron microscopic studies. J Rheumatol 1877;4:261-271.
30. Li-Yu J, Clayburne GM, Sieck MS, et al. Calcium apatite crystals in synovial fluid rice bodies. Ann Rheum Dis 2002;61:387-390.
31. Schumacher HR, Cherian PV. Transmission electron microscopic studies on articular calcium crystals and associated protein coatings. Scanning Electron Microscopy 1984;11:965-968.
32. Uhthoff Hk, Sarkar K, Maynard JA. Calcifying tendonitis: A new concept on pathogenesis Clin Orthop 1976;118:164-.
33. Halverson PB. Basic calcium phosphate (apatie, octacalcium phosphate) crystal deposition diseases and calcinosi. In: Koopman WJ, Moorland LW, eds. Arthritis and allied conditions. 15th ed. Philadelphia: Lea & Febiger, 2005:2397-2416.
34. Halverson PB, Grancis JC, McCarty DJ. Histopathologic and ultrastructural studies of Milwaukee shoulder syndrome-a basic calcium phosphate crystal arthropathy. Ann Rheum Dis 1984;43: 734-741.
More References Related to CPPD
Schumacher HR. The synovitis of pseudogout: electron microscopic observations. Arthritis & Rheumatism 11:426-435, 1968.
Schumacher HR: Ultrastructural findings in chondrocalcinosis and pseudogout. Arthritis Rheum 19:413-425, 1976.
Schumacher HR, Bonner H, Thompson JJ, Kester WL, Benner JJ: Tumor-like soft tissue swelling of the distal phalanx due to calcium pyrophosphate dihydrate crystal deposition. Arthritis Rheum 27:1428-1432, 1984.
Wise CM, Wheeler GE, Irby WR, Schumacher HR: Synovial osteochondromatosis and pseudogout. J Rheumatol 11:229-232, 1984.
Beutler A, Rothfuss S, Clayburne G, Sieck M, Schumacher HR: Calcium pyrophosphate dihydrate crystal deposition in synovium. Relationship to collagen fibers and chondrometaplasia. Arthritis Rheum 36: 704-715, 1993.
Li-Yu J, Schumacher HR, Gratwick G: Invasive tophaceous pseudogout in the temporomandibular joint: misdiagnosis as tumor. J Clin Rheumatol 6: 272-277, 2000.
Yamakawa K, Iwasaki H, Masuda I, Ohjimi Y, Honda I, Saeki K, Zhang J, Shono E, Naito M & Kikuchi M: The utility of alizarin red S staining in calcium pyrophosphate dihydrate crystal deposition disease. J Rheum 30:1032-1035, 2003.
Netter P, Bardin T, Bianchi A et al. The ANKH gene and familial calcium pyrophosphate dihydrate deposition disease. Joint Bone Spine 71:365-368, 2004.
Ea H-K and Liote F. Calcium pyrophosphate dihydrate and basic calcium phosphate crystal-induced arthropathies: update on pathogenesis, clinical features, and therapy. Current Rheumatology Reports 6:221-227, 2004
© The Trustees of the University of Pennsylvania || Template Design: SOMIS Web Team