Research Article
Volume 9 Issue 4 - 2022
Crystal Deposits in Tissue of 64 Patients with Gout - A Comparative Study of Standard Stains and Histochemical Reactions with the Non-Staining Technique of Bély and Apáthy

Miklós Bély1 and Ágnes Apáthy2*

1Department of Pathology, Hospital of the Order of the Brothers of Saint John of God in Budapest
2Department of Rheumatology, St. Margaret Clinic Budapest, Hungary

*Corresponding Author: Ágnes Apáthy, Department of Rheumatology, St. Margaret Clinic Budapest, Hungary.
Received: May 20, 2022; Published: May 30, 2022


The probability of identifying crystals is much higher in unstained histologic sections viewed under polarized light than in haematoxylin-eosin or other conventionally stained ones.

The aim of this study was to describe the characteristic histology of MSU [NaC5H3N4O3·H2O] crystal deposits by conventional staining and by histochemical reactions in tissue samples of patients with clinically diagnosed gout, and to compare these conventionally fixed and stained tissue sections with unstained sections

according to Bély and Apáthy.

Patients and Methods: One hundred and five (105) surgical specimens of 64 patients with clinically diagnosed gout were studied.

Results and Conclusions: Bély and Apáthy’s „non-staining” technique is a simple and effective method to demonstrate crystal deposits in traditionally (formalin) fixed tissue samples.

The histology of MSU (monosodium urate monohydrate [NaC5H3N4O3·H2O] – monosodium salt of uric acid [C5H4N4O3]) crystal deposits is characteristic, accompanied by or without inflammatory reaction.

The microscopic diagnosis of tophus may be difficult in case of atypical clinical symptoms and/or without demonstrable MSU crystals.

The demonstration of minimal amounts of MSU crystals, in unstained sections by Bély and Apáthy’s non-staining technique may be successful, especially in the deeper layers of ptocessed tissue samples.


Keywords: Gout; Monosodium Urate (MSU); Uric Acid; Non-Staining Technique; Traditional Staining And Histochemical Methods


  1. Bély M and Krutsay M. “Az urát-kristályok kimutatásának egyszerű módszere formalin fixált szövetmintákon (A simple method to detect urate crystals in formalin fixed tissue)”. Lege Artis Medicinae (LAM)5-6 (2013): 271-275.
  2. Bély M and Krutsay M. “A simple method to demonstrate urate crystals in formalin fixed tissue”. Journal of Autoimmune Diseases and Rheumatology (JADR)2 (2013): 46-49.
  3. 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, Hoeber PB Inc, New York, Editors: McManus JFA, Mowry RW (1960): 55-72.
  4. Carson FL. “Mayer’s hematoxylin” and “Gömöri’s methenamine silver method for urates”. In Histotechnology, ASCP Press, Chicago, Editor: Carson FL (1990): 100-103.
  5. Lillie RD. “Von Kóssa’s method” and “Uric acid and urates; Schultz staining”. In Histpathologic technic and practical histochemistry, The Blakiston Division McGraw-Hill Book Company, New York, Toronto, London, Editor: Lillie RD (1954): 264-265.
  6. Pearse AGE. “Hexamine silver method for uric acid”. In: Histochemistry theoretical and applied, Churchill Livingstone, Edinburgh, London, Melbourne and New York, Editor: Pearse AGE (1985): 1012-1026.
  7. Vacca LL. “Alizarin red S” and “De Galantha’s method” In Laboratory manual of histochemistry, Raven Press, New York, Editor: Vacca LL (1985): 333-334.
  8. Bély M and Apáthy Á. “Mönckeberg sclerosis – kristály indukálta angiopathia (Mönckeberg‟s sclerosis: crystal-induced angiopathy)”. Orvosi Hetilap23 (2013): 908-913.
  9. Bély M and Apáthy A. “Functional Role of Hydroxyapatite Crystals in Monckeberg's Arteriosclerosis”. Journal of Cardiovascular Disease5 (2014): 228-234.
  10. Bély M and Apáthy Ά. “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.
  11. 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.
  12. 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 Diseases2 (2018).
  13. 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 Bely and Apáthy”. BAOJ Clinical Trials 4 (2021): 018.
  14. Bély M and Balogh K. “Calcification and crystal deposition of aortic valves in clinically latent metabolic disease – A case report”. EC Cardiology6 (2021): 40-47.
  15. Bély M and Apáthy A. “Vascular calcification and crystal deposition diseases - A comparative study on 67 amputated legs with atherosclerosis and/or Mönckeberg sclerosis”. EC Cardiology10 (2021): 01-19.
  16. Lentner C. “Statistical methods”. In Geigy scientific tables, 8th revised and enlarged edition: Ciba-Geigy Limited, Basle, Switzerland, Editor: Lentner C, Compiled by: Diem K, Seldrup J 2 (1982): 227.
  17. Schumacher HR. “Crystal-induced arthritis: an overview”. American Journal of Medicine 2A (1996): 46S-52S.
  18. Gupta SJ. “Crystal induced arthritis: an overview”. INJR (Indian Journal of Rheumatology - Formerly: Journal of Indian Rheumatology Association 10 (2002): 5-13.
  19. Gardner DL and McClure J. “Metabolic nutritional and endocrine diseases of connective tissue, Crystal deposition disease, Urate deposition disease, Calcium pyrophosphate dehydrate crystal deposition disease (chondrocalcinosis; pseudogout), Calcifying tenosynovits, Calcium hydroxyapatite and articular disease”. In Pathological basis of the connective tissue diseases, 1st edition.: Edward Arnold, London, Melburne, Auckland, Great Britain, Editor: Gardner DL 10 (1992): b378-380.
  20. Mohr W. “Gicht“, „Kalziumpirophosphat-Arthropathie“, „Apatitkrankheiten“ In Gelenkpathologie, historische Grundlagen, Ursachen und Entwicklungen von Gelenkleiden und ihre Pathomorphologie, Berlin, Heidelberg, Springer-Verlag, Germany, Editor: Mohr W (2000): 181-193.
  21. Fassbender HG. “Crystal induced arthropathies, Gout, Calcium pyrophosphate dehydrate crystal deposition disease, Hydroxyapatite crystal deposition disease”. In Pathology and pathobiology of rheumatic diseases, 2nd edition. Berlin, Heidelberg, New York, Springer-Verlag, Germany, Editor: Fassbender HG 17 (2002): 353-369.
  22. Neogi T., et al. “2015 Gout Classification Criteria”. Arthritis and Rheumatology10 (2015): 2557-2568.
  23. Martillo MA., et al. “The Crystallization of Monosodium Urate”. Current Rheumatology Report400 (2014).
  24. Reginato AJ and Reginato AM. “Gout and hyperuricemia” and “Diseases associated with deposition of calcium pyrophosphate or hydroxyapatite”. In Crystal-associated synovitis, Section XV, Kelly’s Textbook of Rheumatology, 6th edition. WB Saunders Company: A division of Harcourt Brace and Company, Philadelphia, London, New York, St. Louis, Sydney, Toronto, Editors: Ruddy Sh, Harris ED jr, Sledge CB (2001): 1339-1376.
  25. Mituszova M., et al. “Köszvény és rheumatoid arthritis együttes elôfordulása”. Orvosi Hetilap 122 (1981): 339-342.
  26. Balogh K. (Personal communication (2013).
Citation: Miklós Bély and Ágnes Apáthy. “Crystal Deposits in Tissue of 64 Patients with Gout - A Comparative Study of Standard Stains and Histochemical Reactions with the Non-Staining Technique of Bély and Apáthy”. EC Gynaecology 9.4 (2022): 01-19.

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