EC Pulmonology and Respiratory Medicine

Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C) and primary synovial chondromatosis (prSynCh) are metabolic arthropathies caused by hydroxyapatite (HA) and/or by calcium pyrophosphate dihydrate (CPPD) crystal deposition.

The crystal deposits can be connoted with amorphous calcium phosphate [CaPO₄], calcium carbonate [Ca₃(PO₄)₂] deposits, chondroid and/or bone formation.

Objective of the Study: The object of this microscopic study was

• To ascertain the presence of HA and CPPD crystal deposits in AR, Ch-C and prSynCh viewed under polarized light in conventionally fixed tissue sections stained with HE, and with the technique of Bély and Apáthy (2013).
• To appraise the mineralization, chondroid and/or bone formation in tissue sections of AR, Ch-C and prSynCh with HE, Alizarin Red S, and the von Kossa reaction.

Patients and Methods: At the National Institute of Rheumatology and at the Hospital of the Order of the Brothers of Saint John of God surgical specimens of 101,855 patients were examined histologically between 1985 and 2010; among them were 5 patients with the clinical diagnosis of AR (0.0049%), 16 patients with Ch-C (0.016%), and 20 patients with prSynCh (0.020%).

Tissue samples of 47 joints (28 knee, 10 hip, 4 shoulder, 3 elbow, 2 wrist) of 41 patients with AR, Ch-C or with prSynCh were selected for this study.

Results: HA and/or CPPD crystals were found only occasionally in a few tissue sections stained with HE, while different amounts were demonstrated with Bély and Apáthy’s non-staining technique (2013) in all patients with the clinical diagnosis of AR, Ch-C or prSynCh.

The amount of deposited calcium phosphate and/or carbonate was minimal in patients with prSynCh compared to the mineral deposits of patients with AR or with Ch-C.

Abundant chondroid and/or bone formation was characteristic to prSynCh in contrast with AR or with Ch-C.

Conclusion: The sensitivity of the non-stained section technique is a significantly better method for detection of HA or CPPD crystals than the HE stain.

The authors assume that prSynCh is an abnormal variant of an HA and CPPD induced metabolic disorder with reduced mineralization capabilities, in contrast to AR or Ch-C; the deficient mineralization is replaced by chondroid and/or bone formation.

Keywords: Apatite Rheumatism; Chondrocalcinosis; Primary Synovial Chondromatosis; Conventional Stains and Histochemical Methods; Non-Staining Technique

1. Bély M and Apáthy A. “Crystal deposits in tissue of patients with chondrocalcinosis and apatite rheumatism – Microscopic identification of CPPD and HA with the non-staining technique of Bély and Apáthy”. BAOJ Clinical Trials 4 (2016): 018.
2. Bély M and Apáthy A. “Metabolic Diseases and Crystal Induced Arthropathies Technic of Non-Staining Histologic Sections - A Comparative Study of Standard Stains and Histochemical Reactions”. Clinical Archives of Bone and Joint Diseases (2018): 2.
3. Bély M and Apáthy A. “Crystal deposits in primary synovial chondromatosis”. Annals of the Rheumatic Diseases1 (2022): 1642.
4. Bély M and Apáthy Á. “Apatite rheumatism and chondrocalcinosis are different stages of the same metabolic disorder – A clinicopathologic study of 21 patients with clinically diagnosed apatite rheumatism or chondrocalcinosis”. Journal of Interdisciplinary Histopathology8 (2022): 1-14.
5. Bély M and Apáthy Ά. “Calcium Hydroxyapatite and Calcium Pyrophosphate Dihydrate Crystals in Primary Synovial Chondromatosis”. EC Pulmonology and Respiratory Medicine8 (2022): 05-23.
6. Carson FL. “Mayer’s hematoxylin”. In: Histotechnology (Editor: Carson FL), ASCP Press: Chicago (1990): 100-103.
7. McManus JFA and Mowry RW. “Methods of general utility for the routine study of tissues”, “Sodium Alizarin sulfonate stain for calcium” and “Von Kossa’s method for phosphates and carbonates” In: Staining methods, histologic and histochemical (Editors: McManus JFA, Mowry RW), Hoeber PB Inc, New York (1960): 55-72.
8. Vacca LL. “Alizarin red S”. In: Laboratory manual of histochemistry (Editor: Vacca LL), Raven Press, New York (1985): 333-334.
9. Lillie RD. “Von Kóssa’s method”. In: Histopathologic technic and practical histochemistry (Editor: Lillie RD), The Blakiston Division McGraw-Hill Book Company, New York, Toronto, London (1954): 264-265.
10. Bély M and Apáthy Á. “Mönckeberg sclerosis – kristály indukálta angiopathia (Mönckeberg‟s sclerosis: crystal-induced angiopathy)”. Orvosi Hetilap23 (2013): 908-913.
11. Bély M and Apáthy Á. “A Simple Method for the Microscopic Identification of Calcium Pyrophosphate Dihydrate and Hydroxyapatite Deposits in Metabolic and Crystal Induced Diseases”. Annals of the Rheumatic Diseases 73 (2014): 1081.
12. Bély M and Apáthy Á. “A Simple Method of Diagnostic Pathology for Identification of Crystal Deposits in Metabolic and Crystal Induced Diseases”. Structural Chemistry and Crystallography Communication 2 (2016): 1-15.
13. Swan A., et al. “Submicroscopic crystals in osteoarthritic synovial fluids”. Annals of the Rheumatic Diseases7 (1994): 467-470.
14. Pay S and Terkeltaub R. “Calcium pyrophosphate dihydrate and hydroxyapatite crystal deposition in the joint: New developments relevant to the clinician”. Current Rheumatology Reports3 (2003): 235-243.
15. Gatter RA and Schumacher HR. “Microscopic findings under compensated polarized light and phase light”. In: A practical handbook of joint synovial fluid analysis (Editors: Gatter RA, Schumacher HR), 2^nd: Lea and Febiger, Philadelphia, London (1991): 46.
16. Uhthoff HK and Loehr JW. "Calcific Tendinopathy of the Rotator Cuff: Pathogenesis, Diagnosis, and Management". Journal of the American Academy of Orthopedic Surgeons4 (1997): 183-191.
17. Lentner C. “Statistical methods”. In Geigy scientific tables, 8^th revised and enlarged (Editor: Lentner C, Compiled by: Diem K, Seldrup J) Ciba-Geigy Limited, Basle, Switzerland 2 (1982): 227.
18. McCarty DJ. “Crystals and arthritis”. Disease-a-Month: DM6 (1994): 255-299.
19. Reginato AM and Yuvienco C. “Hydroxyapatite Crystal-Induced”. Rheumatology (2022).
20. McCarty DJ., et al. “Milwaukee shoulder”. Arthritis and Rheumatology3 (1981): 464-473.
21. Dieppe PA., et al. “Apatite associated destructive arthritis”. Rheumatology2 (1984): 84-91.
22. Rosenthal A., et al. “Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease”. UpToDate (2022).
23. “Synovial Chondromatosis - OrthoInfo – AAOS.
24. Wald A. “Sequential analysis. Wiley Mathematical Statistics Series, Chapman abd Hall, New York (1947).
25. Garcia GM., et al. “Hydroxyapatite crystal deposition disease”. Seminars in Musculoskeletal Radiology3 (2003): 187-193.
26. Bachmann D and Resnick D: “Calcium pyrophosphate dihydrate crystal deposition disease”. and “Calcium hydroxyapatite crystal deposition disease”. In: Radiological atlas of rheumatological diseases (Editors: Bachmann D, Resnick D), Editions Roche, F. Hoffmann-La Roche Ltd., Basel, Switzerland (1994): 108-116.
27. https://www.mayoclinic.org/diseases-conditions/pseudogout/symptoms-causes/syc-20376983