- Giant cells are large multinucleated cells formed by the fusion of macrophages in response to infection or foreign material. - There are physiological giant cells like osteoclasts and pathological giant cells seen in conditions like tuberculosis. - Pathological giant cells include foreign body giant cells, Langhans giant cells, and tumor giant cells. - Giant cells form through the fusion of macrophages mediated by cytokines, adhesion molecules, and oxidative stress. Nuclei and inclusion bodies can provide clues to the etiology of giant cell formation.

1. GIANT CELLS
D R A M I T H A G , B D S , M D S
D E P T O F O R A L A N D M A X I L L O FA C I A L PAT H O L O G Y

2. CONTENT :
• Definition
• Morphology and ultra structure
• Types of giant cell
• Formation of giant cell
• Inclusion bodies of giant cell
• Giant cell in detail

3. GIANT CELLS
• It’s a mass formed by the union of
several distinct cells (usually
macrophage).
• And usually arise in response to an
infection.
Merriam – Webster - Dictionary
• Giant cell as an unusually large cell,
especially a large multinucleated
often phagocytic cell.

4. MORPHOLOGY AND ULTRA
STRUCTURE:A) Cell wall :
• Mature giant cell wall is from five to ten times thicker than the cell wall of the
surrounding cells
• Cell wall has irregular surface with numerous projections jutting into the cytoplasm.
B) Cytoplasm :
• Its dense and granular and contain protein
• Contain RNA
• Traces of carbohydrate and fat.

5. C) Under Electron microscope :
Mitochondria
Golgi bodies
Dense endoplasmic reticulum
D) Nucleus and nucleoli:
Its large and irregular in shape
Contain large nucleolus

6. History:
• Giant cells were first described by Virchow (1845)
• Paget called the cells myeloid.
• Malassez and Ritter believed that the giant cells were derived
from modified endothelium.

7. TYPES OF GIANT CELLS
• Physiological Giant Cells:
– Osteoclast
– Megakaryocytes
– Striated Muscle
– Synctiotrophoblast
• Pathological Giant Cells:
– Langhan’s Giant Cell
– Foreign Body Giant Cell
– Touton Giant Cell
– Tumor Giant Cell
– Warthin Finkeldey Giant Cell
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8. FORMATION OF GIANT CELLS
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9. Three mechanisms are put forth to explain the fusion:
Fusion mediated by immune system:
Lymphokines and membrane changes on the cell will facilitate the adherence and
fusion of macrophages.
• Foreign material is antigenic
• If not immune process produces antigen
• Fusion mediated by Lymphokines
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10. 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.
Macrophage
mitosis
Abnormal macrophage
( chromosomal abnormality ) + Young Fusion
( Abnormal cell surface ) Macrophage

11. 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.
A material attached simultaneously to the surface of two macrophages.
Cell membranes of the two fuse
Cell fusion

12. Fusion induced by viruses
Wide variety of Viruses
Large inactive dose or a small active dose
2 possibility
1. Virus in contact with more than one cell membrane
2. Virus penetrates a cell and leads to fusion
( virally coded protein on the cell surface )

13. This complex process induced by
Cytokines:
• IL4, GM-CSF for Foreign body giant cell formation
• IL 3, IFN-Gamma for Langhans giant cell formation
Adhesion Molecules : Beta–integrins, CD36, CD44, CD200
NADPH oxidase : Generates reactive oxygen species (ROS) & play an
important role in macrophage fusion.
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14. 1ST THEORY
• There is multiple division of nucleus without the division of cytoplasm as seen
in tumour giant cells.
• E.G.- Malignant fibrous histocytoma,
And various carcinomas.
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15. 2ND THEORY
• Fusion of multiple cells can occur either from
1. Monocyte/ macrophage lineage
2. Stromal cells in the connective tissue
3. Endothelial cell lining in the blood vessel
4. Undifferentiated reserved stem cells
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16. 16

17. TYPES OF GIANT CELL

18. TYPES OF GIANT CELLS
• Physiological Giant Cells:
– Osteoclast
– Odontoclast
– Megakaryocytes
– Striated Muscle
– Synctiotrophoblast
• Pathological Giant Cells:
– Langhan’s Giant Cell
– Foreign Body Giant Cell
– Touton Giant Cell
– Tumor Giant Cell
– Warthin Finkeldey Giant Cell
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19. 19
Physiological giant cells:
– Osteoclast
– Odontoclast
– Megakaryocytes
– Striated Muscle
– Synctiotrophoblast

20. 20
Pathological Giant Cells:
Foreign body giant cells :
Numerous nuclei (up to 100) which are
uniform is size & shape & resemble the
nuclei of macrophages.
These nuclei are scattered throughout the
cytoplasm.
• seen in response to exogenous material
• Eg : Implants

21. 21
Langhan’s giant cell:
These nuclei are like the nuclei of
macrophage & epitheloid cells.
Nuclei are arranged either around the
periphery in the form of horse shoe or ring,
or clustered at the two pole of the giant
cell.
Examples:
Seen in tuberculosis
Syphilis
Sarcoidosis

22. TOUTON GIANT CELLS
• Macrophages that engulf lipid and cholesterol-rich material
are frequently seen to form multinucleated giant cells that
have foamy, soap bubble like cytoplasm.
• (Greek:xanthos – Yellow; deposition of cholestrol-rich
material) that develop in inflammations affecting the fat
depots.
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23. One variety of such giant cells is a small sized cell with 4-8
nuclei that form a tight cluster near the center of the cell
around a small amount of fatty cytoplasm with more
abundant foamy cytoplasm around the cell
Examples :
Seen in granulomas known as Xanthogranulomas
Tumourous conditions associated with
Hypercholesterolaemia (xanthomas,xanthelasmas).

24. 24
Tumor giant cells
These are larger, have numerous nuclei which are
hyper chromatic & vary in size & shape.
These giant cells are not derived from macrophages
but are formed from dividing nuclei of the neoplastic
cells.

25. 25
Examples are:
– Giant Cell Anaplastic Carcinomas of lung and liver
– Highly malignant sarcomas like liposarcoma, rhabdomyosarcomas, chondrosarcomas contain
extremely atypical and bizarre looking giant cells with multilobed and dark coloured nuclei
– Choriosarcoma, tumour of the trophoblastic cells
– Malignant astrocytoma (glioblastoma multiforme) in the brain
– Fibrous Histiocytoma, there are smaller giant cells derived from histiocytes

26. WARTHIN-FINKELDEY GIANT CELLS
• Have high N: C ratio
• Crowded, irregular nuclei
• Thin filaments with dense bodies
• Desmosomes and cilia present
• Examples:
seen in measles
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27. • 20-50 micrometers in diameter, amphophilic, finely
granular/ homogeneous cytoplasm.
• Two mirror image nuclei (owl eyes) each with an
eosinophilic nucleolus and a thick nuclear membrane
(chromatin is distributed at the cell periphery)
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28. VARIANT OF REED STERNBERG CELL
• The lymphocytic and histiocytic cells (L & H), or Popcorn cells (their nuclei resemble an exploded
kernel of corn) are seen within a background of inflammatory cells, predominantly benign lymphocytes.
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29. MONONUCLEAR REED STERNBERG CELLS
They are identical to Reed sternberg cells except that
they possess a single round or oval nucleus.
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30. PLEOMORPHIC REED-STERNBERG CELLS
Have large, bizarre, Polypoid nuclei typical of
Lymphocyte depletion
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31. HISTOGENISIS
• Its controversial: histiocyte, interdigitating dendritic cell, myeloid cell
and lymphocyte have all been implicated as probable cell of origin.
• Recent study suggest they are majority of B cell linage.
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32. IMMUNOHISTOCHEMISTRY
RS cells are :
• CD45
• CD30
• CD15
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33. 33
• Asteroid bodies are found in giant cells 2–9% of the
cases.
• Star shaped, with radiating lines in the vacuolated
area of cytoplasm of multinucleate giant cells
• peripheral pointed arms converge and appear to
criss-cross at the centre
INCLUSION BODIES IN GIANT CELLS

34. • Colorless, refractile crystals composed
predominantly of calcium oxalate are
frequently found in the giant cells of
granulomas of sarcoidosis and other
diseases.
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35. • The oxalate crystals may help in deposition of calcium
leading to formation of Schaumann bodies.
• Large concentric calcifications often containing
refractile calcium oxalate crystals
• Usually intracytoplasmic, if numerous or very large, be
extruded into the extracellular space
• Ultrastructural studies have shown that H-W bodies are
giant lysosomes and residual bodies.
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36. • Yellow-brown bodies/ Chromogenic bodies .
• Found in epithelioid cells and macrophages.
• Oval or spindle-shaped
• Thought to be a giant lysosome.
• They are degenerated lysosomes, with no
recognized clinical significance.
• Positive with H and E stain.
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37. THANK YOU