GIANT CELLS

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

1. Giant cellS dr Amitha G, BDS, MDS Dept of oral and maxillofacial pathology

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 7

8. Formation of Giant Cells 8

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 9

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. 13

14. 1 st 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. 14

15. 2 nd Theory Fusion of multiple cells can occur either from Monocyte/ macrophage lineage Stromal cells in the connective tissue Endothelial cell lining in the blood vessel Undifferentiated reserved stem cells 15

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 18

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. 22

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 26

27. Reed sternberg cell 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) 27

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. 28

29. Mononuclear reed sternberg cells They are identical to Reed sternberg cells except that they possess a single round or oval nucleus. 29

30. Pleomorphic reed- sternberg cells Have large, bizarre, Polypoid nuclei typical of Lymphocyte depletion 30

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. 31

32. Immunohistochemistry RS cells are : CD45 CD30 CD15 32

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 ASTEROID BODIES INCLUSION BODIES IN GIANT CELLS

34. OXALATE CRYSTALS Colorless, refractile crystals  composed predominantly of calcium oxalate are frequently found in the giant cells of granulomas of sarcoidosis and other diseases. 34

35. SCHAUMANN BODIES 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. 35

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. 36 HAMAZAKI-WESENBERG BODIES

37. THANK YOU