This document discusses giant cell formation and function. It begins with definitions of giant cells as unusually large cells with multiple nuclei. It then classifies giant cells into categories such as damaged muscle fibers, tumor giant cells, fused cells from viral infections, and fused macrophages. The mechanisms of giant cell formation including fusion mediated by cytokines and adhesion are explored. Individual giant cell types like osteoclasts, tumor giant cells, foreign body giant cells and Langhans giant cells are described in terms of morphology, markers and function. The document concludes that further studies are needed to fully understand giant cell formation through paracrine, juxtacrine and endocrine interactions.

1. Giant cell formation and function
Dr. Madhusudhan Reddy,
Senior lecturer,
Lenora dental college,
Rajahmundry.

2. Contents
• Introduction
– Definition
• Classification of giant cells
• Mechanism of formation
• Individual giant cells
• Conclusion
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3. Introduction
• Definition: Giant cells can be described as an unusually
large, huge or gigantic cell as a large multinucleated often
phagocytic cell.
• First described by Virchow
• Synonyms – Polykaryocytes and Syncytium
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4. Introduction
• light microscope
– Measures 40-50 µm
– Multiple nucleus (up to 100)
– Eosinophilic cytoplasm
• Union of several distinct cells. (monocyte macrophage
lineage)
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5. Introduction
• Number of nucleus depends on the mechanism of their
formation
• Seen when macrophages are not able to engulf the foreign
material in extravascular tissue
• Involved in number of physiological and pathological
processes
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6. Classification of giant cells
• J B Walter and M S Israel (1979) classified giant cells as,
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I) Damaged
Striated Muscle
Fibers:
1) Regenerating sarcolemmal cells in damaged
voluntary muscle.
2) Aschoff giant cells in heart muscle (fused
myocardial macrophage).
II) Tumor Giant
Cells:
1) Giant cell tumors e.g. bone, poorly
differentiated astrocytoma (glioblastoma
multiforme), choriocarcinoma, Hodgkin’s disease
(Reed – Sternberg cell) etc.
2) Giant cell variants of many tumors e.g.
carcinoma of lung and kidney.

7. Classification of giant cells
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III) Fused cells in
viral infection:
1) Epithelial giant cells e.g. in herpes virus
infection
2) Connective tissue giant cells e.g. Warthin -
Finkeldey giant cells of measles
IV) Fused
macrophages:
1) Reaction to exogenous insoluble material e.g.
talc, silica and ligatures (foreign body giant
cells)
2) Reaction to insoluble material formed in the
body e.g. sodium urate crystals, cholesterol,
keratin and fat.
3) Touton giant cells
4) Reaction to certain organisms e.g. tuberculosis
(Langhans giant cell), fungal infections and
syphilis.

8. Classification of giant cells
I) Tumor giant cells II) Fused Macrophages
1) Reed- Sternberg cells in
hodgkin’s lymphoma
2) Giant cells in central giant
cell granuloma, poorly
differentiated astrocytoma
3) Giant cells in other tumors
eg: malignant fibrous
histiocytoma
1) Due to reaction to foreign
bodies
2) Due to reaction to organisms
as in tuberculosis
3) Touton giant cells of
xanthoma
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• Chattopadyay (1995) classified giant cells

9. • Giant cells can also classified based on their occurrence in
the body into,
• Physiological giant cells:
Osteoclasts
Odontoclasts
Striated muscle
Synctiotrophoblast
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Classification of giant cells

10. 21/3/2015 Dr.Madhusudhan reddy 11

11. • Pathological Giant Cells:
– Foreign body giant cell
– Langhans giant cell
– Tuton giant cell
– Tumor giant cell
– Miscellaneous types
• Eg: Reed-Sternberg cells, Warthin Finkeldy giant
cells
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Classification of giant cells

12. Formation of giant cells
• Giant cell formation represented an adaption of improved
phagocytosis.
• Few proposed mechanisms:
• Singer and Nicolson (1872) stated that the cell membrane
consists of a lipid bilayer in which the protein floats with
varying degrees of lateral mobility. This lipid layer needs to
be reconditioned by some destabilizing process so that it
can fuse with other bilayer.
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13. • Heine and Schnaitman (1971) suggested that the antigens
from the viral envelope becomes incorporated into the
polykaryon membrane showing that the fusion results
from the viral envelope forming a bridge between two cells.
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Formation of giant cells

14. how are giant cell formed?
Three mechanisms are put forth to explain the fusion:
1. Fusion mediated by immune system: Lymphokines and
membrane changes on the cell will facilitate the adherence
and fusion of macrophages.
2.Fusion from recognition of an abnormal macrophage
surface by young macrophage: Chromosome abnormalities
lead to the formation of an abnormal cell surface. This is
recognised by fresh/ young macrophage and fusion occurs.
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15. • 3. Fusion due to endocytic activity: An endosome margin is
formed when antigen attaches to the surface of the
macrophage. One endosome margin fuses with the other
and fusion takes place.
how are giant cell formed?
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16. Why fusion occurs?
• It is a complex process induced by
– Cytokines
• IL4, GM-CSF – Foreign Body Giant Cell Formation
• INF-GAMMA, IL3 – Langhans Giant Cell Formation
– Adhesion Molecules: Beta – Intigrins, CD36, CD44, CD200
– NADPH Oxidase: Generates Reactive Oxygen Species
(ROS) And Play An Important Role In Macrophage
Fusion
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17. Cumhuriyet Dent J 2014;17(2):192-204

18. J Innate Immun 2009;1:509–526

19. • Study- high levels of matrix metalloproteinase (MMP -9)
during macrophage fusion in vitro and in foreign body
giant cells (FBGCs) in vivo.
April 2009 Journal of Leukocyte Biology vol. 85 no. 4 617-626
• Protein kinase C may play an important role in the
formation of macrophage-derived MGC.
The Journal of Immunology October 1, 1989 vol. 143 no. 7 2179-2184
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20. • Recent studies involving mainly osteoclasts and foreign
body giant cells have revealed a number of common
factors, for example, vitronectin, an adhesion protein,
dendritic cell-specific transmembrane protein (DC-
STAMP), a fusion factor, and macrophage fusion receptor,
that contribute to giant cell formation and function.
Current opinion in hematology, 2009, vol.16, 53-61.
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21. • Among the cytokines that have been found to induce or
benefit monocyte fusion, IFN-γ has a prominent role.
Blood, Vol 89, No 2 (January 15), 1997: pp 662-671
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22. Giant cells
• Osteoclasts
• Tumor giant cells
• Touton giant cells
• Langhans giant cells
• Foreign body giant cells
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23. Osteoclasts
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24. Osteoclasts
• Named by Kolliker
• Bone resorbing cell – bone homeostasis
• Osteoclast precursors – derived from bone marrow
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J Med Dent Sci 2012； 59： 65－74, Cumhuriyet Dent J 2014;17(2):192-204

25. Formation of osteoclast
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J Med Dent Sci 2012； 59： 65－74,
Cumhuriyet Dent J 2014;17(2):192-204,
Curr Opin Hematol. 2009 January ; 16(1): 53–57.

26. osteoclasts
• Morphologically osteoclasts are similar to foreign body
giant cells
• Contain fewer nucleus (10-20)
• Seen endosteal surface of haversian system, periosteal
surface;
• Positive for: Cathepsin K, alkaline phosphatase, RANKL,
osteoprotegerin, CD68.
• Specific marker – Calcitonin receptor
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Cumhuriyet Dent J 2014;17(2):192-204

27. Tumor giant cells
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28. Tumor giant cells
• Seen in epithelial and mesenchymal neoplasms
• Numerous nuclei, hyper chromatic & vary in size & shape.
• Not derived from macrophages but are formed from
dividing nuclei of the neoplastic cells.
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• Tumor cells with abnormal surfaces
predisposed to fusion in different ways

29. Tumor giant cell formation
• Tumor cell release
Extracellular enzymes
Reduce the surface coat thickness
Close approximation of lipid bilayer
• Some tumors are associated with Passenger viruses -
Causes cell fusion
Cumhuriyet Dent J 2014;17(2):192-204
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30. Seminars in Diagnostic Pathology, Vol 30, No 1,
February 2013
Types of tumor giant cells
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Touton type of
tumror giant cell
Osteoclast-like
tumor giant cell
Floret-like
tumror giant cell
Glassy tumror
giant cell

31. Floret Like MGC In
Pleomorphic Lipoma
Floret Like MGC In giant
cell fibroblastoma
Seminars in Diagnostic Pathology, Vol 30, No 1,
February 2013
Osteoclast like MGC in atypical
fibroxanthoma
Histiocyte like MGC in atypical
fibroxanthoma
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32. Tumor giant cell
• Josten M & Rudolph R studied canine and feline neoplasia
to differentiate the giant cell by using MIB1, TRAP
• Neoplastic giant cells – positivity to MIB1 but not for
TRAP
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33. Touton giant cells
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34. 21/3/2015 Dr.Madhusudhan reddy 35
Touton giant cells
• The cell was named after Karl Touton
• Clustered nuclei in the cell surrounded by foamy cytoplasm
• Originally known as Xanthelasmatic giant cells
• Lesions containing cholesterol and lipid diposits
• Frequently found – Xanthomas, Xanthogranulomas, fibrous
histiocytoma

35. Formation of Touton giant cells
• Formed by fusion of macrophages derived from foam cells
• Cytokines – Interferon gamma, IL-3 and M-CSF
J Innate Immun 2009;1:509–526
• Lipid droplets in Cells are demonstrated in frozen section
by special stains
• Differentiated from other cells by markers
– Lysozyme
– Α1 antitrypsin
– CD68 and
– Factor XIIIa
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:246-252.
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36. Langhans giant cells
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37. Langhans giant cells
• Named after Theodor Langhans (German pathologist)
• Characterized by presence of < 20 nuclei arranged
peripherally in the cytoplasm
• Seen in immune granulomas and granulomatous
inflammation
• Indigestable particles of organisms eg: tubercle bacilli
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38. Formation of Langhans giant cells
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International Immunology, Vol. 24, No. 1, pp. 5–15

39. Appearance of langhans giant cells
• Nuclei are arranged around the periphery of cytoplasm in
the form of
– Horse shoe or ring,
– Clustered at the two pole of the cell
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40. • These cells show positivity to CD68
• According to Lay et al
• Larger cells with more nuclei – virulence of the disease
increases
• Mycobacterium tuberculosis – large MGCs ( >15 nuclei)
• Granuloma formation and phagocytic activity absent
• Mycobacterium avium and smegmatis – (<7 nuclei)
phagocytic activity present
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Current opinion in hematology, 2009, vol.16, 53-61.

41. Foreign body giant cells
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42. Foreign body giant cells
• Generated by fusion of macrophages
• Serve for degradation/resorption of underlying substrate
• Similar to osteoclasts
• Seen in tissues where the size of foreign particulate is too
large to permit macrophage phagocytosis
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43. • Numerous nuclei (up to 100), uniform is size & shape
resemble the nuclei of macrophages.
• These nuclei are scattered throughout the cytoplasm.
• They are seen in chronic infective granuloma, leprosy &
tuberculosis
appearance of foreign body giant cells
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44. Formation of foreign body giant cells
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Semin Immunol. 2008 April ; 20(2): 86–100.
IL-4, IL-13

45. 21/3/2015 Dr.Madhusudhan reddy 46
Semin Immunol. 2008 April ; 20(2): 86–100.
Formation of foreign body giant cells

46. • Observed at the tissue material interface such as
– Medical device – biodegradable polymeric
– Foreign body reaction
• Seen at site of hemorrhage or necrosis
• Associated with atheroma in an attempt to remove
cholesterol crystals
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Function of foreign body giant cells

47. Reed-Sternberg giant cells
• Pathognomonic of hodgkins lymphoma
• Usually derived from B lymphocytes
• Named after Dorothy Reed Mendenhall and Carl Sternberg
• Usually multinucleated or bilobed nucleus with prominent
eosinophilic nucleoli resembling “owl eye”
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48. Warthin-finkleday giant cells
• Virus induced giant cells
• Pathognomonic for measles
• Seen in hyperplastic lymph nodes, tonsils, appendix
• Origin is uncertain
• Cells has large grape like cluster of hyperchromatic nuclei
• Stain with CD21
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Ultrastructural pathology 1988; 22(4): 293-303

49. Conclusion
• Till date Study of giant cells is confusing and complicated
• Many studies done on animal models were inconclusive
• Sound knowledge about
– Paracrine,
– Juxtracrine and
– Endocrine interactions
is necessary for the understanding the formation of
different giant cells.
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50. References
• Cumhuriyet Dent J 2014;17(2):192-204
• J Innate Immun 2009;1:509–526
• April 2009 Journal of Leukocyte Biology vol. 85 no. 4 617-626
• The Journal of Immunology October 1, 1989 vol. 143 no. 7 2179-2184
• Current opinion in hematology, 2009, vol.16, 53-61.
• Blood, Vol 89, No 2 (January 15), 1997: pp 662-671
• J Med Dent Sci 2012； 59： 65－74, Cumhuriyet Dent J
2014;17(2):192-204
• Seminars in Diagnostic Pathology, Vol 30, No 1, February 2013
• Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:246-
252
• International Immunology, Vol. 24, No. 1, pp. 5–15
• Semin Immunol. 2008 April ; 20(2): 86–100.
• The warthin-finkeldey type giant cell in HIV infection, what is it?
Ultrastructural pathology 1988; 22(4): 293-303

51. Acknowledgement
• Dr. T.R.Saraswathi
• Dr. C.R.Ramachandran
• Dr. N.Govind Rajkumar
• Dr. Ravikanth Manyam
• Dr. Bina Kashyap
• Dr. P Swetha
• Dr. A.Nagasupriya
• Dr. T.S.Barath
• Dr. B.Smitha
• Dr. S. Sruthi

52. Acknowledgement

53. Thank “u”