Giant cell & giant cell lesions

1. GIANT CELLS
& GIANT
CELL
LESIONS
Presented by –
DR. NANDINI BHARDWAJ
MDS 2nd Year
Dept of oral and Maxillofacial
Pathology, Microbiology &
forensic odontology

3. GIANT CELL- AN UNUSUALLY LARGE, HUGE
OR GIGANTIC CELL !!!
Cells generally contain a single
nucleus when observed under the
microscope.
Under specific conditions, this
broad generalization is broken i.e.
tissues containing cells in which
several nuclei share the same
cytoplasm
A Giant cell is defined as
an unusually large, huge or
gigantic cell, as a large ,
multinucleated often
phagocytic cell, cell with
more than one nucleus , a
multinucleated mass of
cytoplasm that is not
separated into cells

4. Morphologically
characterized by-
Presence of multiple
nuclei dispersed in
cytoplasm
Giant cells can be
mononucleated or
multinucleated & are
derived from
monocyte/macrophage
precursors
Fusion of
macrophages can
result in the
formation of
Oseoclasts
A variety of MGC’s
each with unique
properties
In chronic inflammation ,
Macrophages fuse
together & form
multinucleated giant cells
(MGC’s) for elimination of
foreign particles and
damaged tissue

5. HISTORY
MULLER J (1838) – Credited with discovery
VIRCHOW & LANGHAN – Discussed there nature
LANGHAN- Deals with their role in tuberculosis and
foreign body reactions & mode of formation
LAMBERT (1912)- Observed the formation of
multinucleated giant cells from mononuclear cells
LEWIS – Transformation of mononuclear cells into giant
cells

7. MGC’s are formed by the fusion of
macrophages & monocyte lineage .
Common in granulomatous inflammation &
are associated with
Immune response to-Tuberculosis ,
Leprosy ,Syphilis , Parasitic & Fungal
Infections
Non- Immune responses –
Toxic agents – Silica, Beryllium, Asbestos
Non- Toxic agents - Carbon particles,
Plastic beads

8. THEORIES FOR ORIGIN OF GIANT CELLS
I. Giant cells may arise from the endothelial cells of
capillaries & from the mitotic and amitotic division of
monocyte nuclei in the absence of cellular division
II. Giant cells may arise from the proliferating giant
cells associated with the resorption of deciduous
tooth
III. Giant cells arise from the fusion of non-
replicating monocytes
SIZE- 40µm- 120µm
Have phagocytic and pinocytic activity

9. In giant cells , all centrioles found in one area
Cytofilaments radiating away from centriole
towards nuclei
Collection of filaments at microscopic level
called ASTEROID BODIES
Secretes interferon's, lysozymes, acid
hydrolyses, neutral proteases
PHENOTYPE – varies depending on local
environment and Physical nature of the agent
to which MGC’s are responding

11. FIRST TYPE –
Contained a central rosette
surrounded by nuclei in the
periphery .
Known as LANGHENS
/EPITHELOID GIANT CELLS
formed due to nuclear division
SECOND TYPE- Irregular
arrangement of nuclei and
were known as FOREIGN
BODY TYPE GIANT CELLS
Arise due to the fusion of
moncytes
FORKNER( 1930) – Found
two types of giant cells in
the blood & tissues of
rabbits

12. Formation of FBGC’S and Langhan's giant cells by fusion & nuclear division

13. RADIO- LABELLING STUDIES –
Revealed that both Langhans &
foreign body giant cells arise due
to fusion of monocytes and not
due to the division with “non-
disjunction”
AUTO- RAGIOGRAPHIC
STUDIES-
Revealed that Giant cells are
formed due to fusion
“CELL FUSION- occurs from an
alteration of cell surface for close
membrane approximation and
establishment of continuity
between apposed lipid bilayers”

14. Formation of different types of Giant cells

15. MECHANISM OF FUSION OF GIANT CELLS
• Fusion of macrophages to form multinucleated giant
cells are caused by production of large amount of
lymphokines.
• Macrophage MGC are found in areas containing
antigenic foreign material ( micro- organisms)
IMMUNE
MEDIATED
MECHANISM
• Fusion occurs between young macrophages and older
cells
• Older cells constitute existing macrophages in
granulomatous environment which acquire
chromosomal abnormalities in the macrophage surface
• The stimulus for cell fusion is the recognition of
abnormal cell surface by young macrophages
YOUNG – OLD
MACROPHAGE
FUSION
• When two or more macrophages try to ingest the
same particle, simultaneous attempted
phagocytosis results in the fusion of endosomal
margins to form multinucleated giant cells
PHAGOCYTOSIS
MEDIATED
MECHANISM

16. Formation of Giant cells following macrophage/ monocytic lineage

17. In case of INACTIVATED VIRUSES –
Direct interaction between the viral
envelope and cell surface
Attachment of viral envelope leads to the
reduction in cell coat thickness & fusion
with cell membrane
Cell fusion occurs if the virus is in contact
with more than one cell
Antigens from the viral envelope
incorporates into polykaryon membrane
results in the fusion between two cells
forming a bridge
Role of viruses in Fusion

19. MGC formation is mediated by Interlacing cell surface proteins on the
fusing macrophages
DC-STAMP – Dendritic cell specific transmembrane
protein required for the fusion of both Oseoclasts and
Foreign body giant cells
Oseoclasts derived from DC-Stamp knock out mice
were mononuclear , exhibits bone resorbing activity ,
Oseoclasts markers but “ NO CELL FUSION”
Depends upon cell to cell contact ( critical density) & local factors ,
growth factors & chemotactic factors
Local factors includes cytokines ( interferon's)- strong
inducer of Oseoclasts like cell differentiation
,Osteoprotegrin
Growth factors includes Macrophage colony
stimulating factor (M-CSF) and colony factors
Mononuclear phagocytes fuse in specific environment i.e.
Bone surface for Oseoclasts Chronic Inflammatory sites for giant cells

20. EXPRESSION OF DC- STAMP is stimulated by osteoclast differenciation factor receptor
activator of nuclear factor Kappa β ligand (RANKL) to which Osteoclasts precursors cell
respond. The ligand for DC- STAMP can be membrane bound or soluble
The DC-STAMP expressing osteoclast becomes
master fusing cell , which can fuse with DC- STAMP
negative follower cell
DC- STAMP ligation induces fusion of two cells directly
or may trigger the expression of unknown membrane
bound molecules ‘X’ that mediates fusion
THESE STUDIES CLEARLY IDENTFIES THAT A COMMON MOLECULE IS NECESSARY
FOR MULTINUCLEATION AND CELL FUSION OF BOTH OSTEOCLASTS AND FBGC’S
Vignery(2005)- identifies a ligand for DC- STAMP
which can be a surface protein expressed by
Macrophages or a soluble protein released by
macrophages
Ligand for DC- STAMP is related to Osteoclasts,
FBGC’S & macrophage interaction with tumor cells
Retroviral introduction of DC- STAMP in Oseoclasts precursors re-established
osteoclast nucleation
Polyvinyl alcohol in DC-STAMP knock out mice results
in withdrawal of multinucleated giant cells
IL-3, IL-4 Treatment of DC- STAMP knock out mice
results in no FBGC’s formation

21. Macrophages respond to IL-4 by inducing
expression of DC- STAMP which facilitates fusion
Osteoclast formation is induced
by RANKL & M-CSF
Osteoclastic giant cells are
positive for Cathepsin K,Alkaline
phosphatase,RANKL,
Osteoprotegrein, CD68
Mechanism of formation of osteoclastic giant cells

23. BASED ON ETIOPATHOGENESIS
I. Chattopadhyay, 1995
A. Where giant cells are present in the
concerned background
and are pathognomic:
1. Hodgkin’s syndrome
2. Peripheral giant cell granuloma
3. Giant cell fibroma
B. Where giant cells are characteristic, but
not pathognomic:-
1. Tuberculosis
2. Herpes simplex virus infection
3. Measles
4. Xanthoma
C. Diseases associated with the presence
of giant cells:
1. Orofacial granulomatosis
2. Fungal infection foreign body reactions
3. Neoplasms
4. Syphilis
5. Leprosy
6. Fibrous dysplasia
7. Cherubism
8. Paget’s disease of the bone
9. Aneurysmal bone cyst
10. Ossifying fibroma
11. Wegener’s granulamatosis
12. Actinomycoses
13. Chronic diffuse sclerosing osteomyelitis
14. Odontogenic giant cell fibromatoses
15. Heerfordt’s syndrome.

24. II. Chatterjee, et al. (2015)
According to Paul Auclair et al. entities in
which giant cells
are the predominant histologic finding and
form the basis of
their recognition:
• Central giant cell granuloma
• Giant cell tumor of bone
• Aneurismal bone cyst
• Cherubism
• Brown tumor of hyperparathyroidism.
Lesions containing giant cells
Infectious diseases:
Bacterial:
• Tuberculosis
• Leprosy
• Syphilis
• Actinomycosis
• Cat scratch disease
Viral:
• Herpes
• Measles
Mycotic:
• Histoplasmosis
• Blastomycosis.

25. III. Varghese and Prakash, 2011
1. Microbial lesions: Tuberculosis, leprosy,
Actinomycosis,
sarcoidosis
2. Tumor and tumor like lesions: Central
giant cell granuloma,
peripheral giant cell granuloma, giant cell
fibroma,
giant cell tumor, osteosarcoma,
rhabdomyosarcoma,
Hodgkin's lymphoma
3. Cystic lesions: Traumatic bone cyst,
Aneurysmal bone cyst
4. Metabolic lesions: Hyperparathyroidism
5. Osteodystrophic lesions: Noonan like
multiple giant cell
lesion syndrome
6. Miscellaneous lesions: Cherubism,
Paget’s disease, fibrous
dysplasia.

26. Based on origin (Gupta, et al., 2014)
1. Macrophage derived:
a. Langhans giant cells
b. FBGCs
c. Touton giant cells: Xanthelasmatic giant
cells
2. Epidermal cell derived:
a. Tzanck giant cells
b. Multinucleated epidermal giant cellsMelanocyte derived:
a. Starburst giant cells
b. Giant cells in melanocytic nevus
i. Balloon cells
ii. Giant nevus cells
4. Other giant cells:
a. Floret like multinucleated giant cells.

27. Based on origin and etiology (Chattopadhyay, 1995)
1. Damaged striated muscle fiber:
a. Regenerating Sarcolemma cells in
damaged voluntary
muscle
b. Aschoff giant cells in heart muscle
(fused myocardial
macrophages)
2. Fused fibroblasts:
Giant cell fibroma
3. Osteoclast:
Paget’s disease
4. Tumor giant cells:
a. Reed–Sternberg cells in Hodgkin's
lymphoma
b. Giant cells in central giant cell
granuloma, poorly
differentiated astrocytoma
c. Giant cells in other tumors, for example,
malignant
fibrous histiocytoma
5. Viral infections:
a. Epithelial giant cells as in HSV infection
b. Connective tissue cells as in measles
(Warthin– Finkeldey cells)
6. Fused macrophages:
a. Due to reaction to foreign bodies
(exogenous or
endogenous materials) for example, FBGC
with
scattered nuclei
b. Due to reaction to organisms as in
tuberculosis
(langhans giant cell) and fungal infections
c. Touton giant cells of Xanthoma.

28. Based on functional characteristics (Sankari, et al.,
2014)
1. Physiologic giant cells:
a. Osteoclast
b. Odontoclast
c. Megakaryocytes
d. Syncytiotrophoblast
e. Skeletal muscle fibers
2. Pathologic giant cells:
a. FBGC
b. Langhans giant cells found in TB
c. Touton giant cells, seen in histocytosis Y
d. Aschoff giant cell, seen in rheumatic
carditis
e. Dorothy reed giant cell, seen in
Hodgkin’s disease
f. Giant cells found in malignancy
g. Giant cells found in viral infection
3. Fused fibroblasts:
Giant cell fibroma
4. Osteoclast:
Paget’s disease
5. Tumor giant cells:
a. Reed–Sternberg cells in Hodgkins
lymphoma
b. Giant cells in central giant cell
granuloma, poorly
differentiated astrocytoma
c. Giant cells in other tumors, for example,
malignant
fibrous histiocytoma
6. Viral infections:
a. Epithelial giant cells as in HSV infection
b. Connective tissue cells as in measles
(Warthin– Finkeldey cells)
7. Fused macrophages:
a. Due to reaction to foreign bodies
(exogenous or
endogenous materials) for example, FBGC
with
scattered nuclei
b. Due to reaction to organisms as in
tuberculosis

29. Based on the type of giant cells present (Mathew, et al.
2016)
I. Epithelial derived viral induced
multinucleated giant cell
containing lesions
1. Tzank giant cells – herpes simplex
2. Tzank giant cells – herpes zoster
II. Monocyte/MGCs containing lesions
1. Inflammatory granuloma associated
giant cells
2. Langhans giant cell containing
pathologies
3. Infections – tuberculosis, leprosy, late
syphilis, deep
fungal infections
4. Unknown antigenic stimuli – sarcoidosis
and
orofacial granulomatosis
5. FBGC containing lesions
6. Foreign body granuloma
7. Osteoclastic giant cell containing lesions
8. Lesions with Osteoclastic giant cells
being the primary
pathologic cells – Paget’s disease
III. Lesions with reactive osteoclastic giant
cells formed
secondarily by the activation of lesional
stromal cells
1. Peripheral and central giant cell
granulomas,
cherubism and aneurysmal bone cyst
2. Fibrous dysplasia, brown tumor of
hyperparathyroidism
• Touton giant cells
• Xanthoma, xanthogranuloma,
fibroushistiocytoma.
• Tumor giant cells
• Tumors where giant cells are
pathognomonic
• Giant cell fibroma, Hodgkin’s lymphoma
• Other anaplastic malignancies.

30. Classification based on arrangement, composition of
organelles and function
I. Haythorn, et al., 1929[10]:
(a) Langhans’ giant cells
(b) FBGC
(c) Osteoclasts
(d) Megakaryocytes
(e) Muscle giant cells
(f) Giant cells of nervous tissue
(g) True tumor giant cells
II. Quinn MT and Schepetkin IA
2009[11]:
(1) FBGCs
(2) Langhans giant cells
(3) Touton giant cells
(4) Osteoclast like cells
(5) Osteoclasts.

31. Based on radiographic appearance (Enneking and
Campanacci, 2016)
Grade – I tumor has a well - marginated border of
a thin rim of
mature bone, and the cortex is intact or slightly
thinned but
not deformed.
Grade – II tumor has relatively well-defined
margins but no
radiopaque rim; the combined cortex and rim of
reactive
bone is rather thin and moderately expanded but
still present.
Grade- II lesions with a fracture are graded
separately.
Grade – III designates a tumor with fuzzy borders,
suggesting a
rapid and possibly permeative growth; the tumor
bulges into the
soft tissues, but the soft - tissue mass does not
follow the contour of
the bone and is not limited by an apparent shell of
reactive bone.

32. Based on pathology involved
I Lucas (1976)
A. Intrabony lesions
a. Giant cell tumor of bone
b. Giant cell granuloma
c. Focal giant cell lesion or “Brown tumor of
hyperparathyroidism”
B. Soft tissue lesions
a. Peripheral giant cell granuloma
b. Giant cell fibroma.
II. Cotran, Kumar and Robbins
1994
1. Giant cells in inflammation:
(a) Foreign body giant cells
(b) Langhan’s giant cells
(c) Touton giant cells
(d) Aschoff giant cells
2. Giant cells in tumor:
(a) Tumor giant cells
(b) Reed–Sternberg cells
(c) Giant cell tumor of bone.

33. III. Rosenberg, et al., 2001
I. Giant cell lesions of bone
A. Reactive:
• Brown tumor
• Hemophiliac pseudo tumor
• Intraosseous haemorrhage
B. Benign:
• Giant cell granuloma
• Non - ossifying fibroma
• Giant cell tumor
II. Mucosal lesions with giant cells
A. Peripheral giant cell granuloma
B. Giant cell fibroma
C. Oral granulomatosis
• Specific: Fungal, bacterial, viral infection
• Non-specific: Sarcoidosis, Wegener ’s
granulomatosis
Xanthogranuloma
A. Hodgkins lymphoma
B. Temporal arteritis.
• Aneurysmal bone cyst
• Chondroblastoma
• Chondromyxoid fibroma
• Langerhans cell histiocytosis
• Pigmented villonodular synovitis
C. Malignant:
• Osteosarcoma
• Clear cell chondrosarcoma
• Metastatic carcinoma

35. DEPENDING UPON THE ARRANGEMENT & COMPOSITION OF
THEIR ORGANELLES
Multinucleated giant
cells can be
classified into
several
morphological
variants
PHYSIOLOGIC GIANT
CELLS
PATHOLOGIC GIANT
CELLS
Multinucleated Giant
Cells that exist in normal
tissues-
Osteoclasts in bone
Trophoblast in placenta
Megakaryocytes in bone
marrow
Odontoclasts
Skeletal muscle Fibers
A. GIANT CELLS IN
INFLAMMATION –
Foreign Body Giant cells
Langhan’s Giant cells
B. GIANT CELLS IN
TUMORS –
Tumor Giant cells
Reed Sternberg cells

36. DIFFERENT TYPES OF GIANT CELLS

38. LESIONS CONTAINING
OSTEOCLASTS-
Central giant cell granuloma
Paget’s Disease
Cherubism
Osteoblastoma
Simple bone cyst
Aneurysmal bone cyst
Giant cell tumor of Bone
DISORDERS RELATED TO
MEGAKARYOCYTES –
Myelodysplastic
syndrome(MDS)
Idiothrombocytopenic
purpura(ITP)
Congenital amegakaryocytic
thrombocytopenia
Familial essential
thrombocytopenia(ET)
GIANT CELL ASSOCIATED TUMORS-
Giant cell reparative granuloma
Villonodular telosynovitis
Fibrous histiocytoma
Osteoclastoma
Medullary Carcinoma of thyroid
Squamous Cell Carcinoma

39. OSTEOCLASTS
Named by Kolliker and are BONE- RESORBING
CELLS
Plays pivotal role in bone homeostasis and
remodelling
Osteoclast precursors are derived from bone marrow
as early mononuclear macrophages, which circulate
in blood and bind to bone surface
Driven by two cytokines – RANKL & M-CSF
MORPHOLOGICALLY- Similar to FBGC’s
Contains 10-20 Nuclei per cell
FOUND ON- Bone surface, Endosteal surface within
the haversion system , periosteal surface beneath the
periosteum
POSITIVE for – Cathepsin K, Alkaline
Phosphatase,RANKL,CD68
More specific Factor – Calcitonin receptor

40. Multinucleated osteoclastic giant cells on the surface of bone

41. FOREIGN BODY GIANT CELLS
FBGC’s contains numerous nuclei(100), uniform in size & shape
resembles macrophage nuclei and are formed by the fusion of
macrophages . Nuclei scattered throughout the cytoplasm.
PURPOSE- Same as Osteoclasts i.e. degradation and resorption of
underlying substrate
When Macrophage encounter insoluble materials, they fuse and coalesce
to form giant cells – MODE OF FORMATION OF GIANT CELLS rather than
nuclear division
DNA synthesis occurs despite the inactive appearing nuclei
Associated with-
Chronic infective granuloma
Tuberculosis
Leprosy
HIV -1 mediated syncytium formation, Warthin Finkeley cells , Reed
Sternberg cells are other multinucleated giant cells associated with HIV,
Rubeola , Hodgkin’s Lymphoma

42. Foreign body giant cells in connective tissue stroma

43. LANGHAN’S GIANT CELLS
Characterized by nuclei like nuclei of macrophages &
epithelioid cells
Nuclei (<20) arranged either around periphery in the form of
horse-shoe, ring or cluster at the two poles of giant cell
Results from the fusion of macrophages giving rise to giant
cell in response to foreign bodies which can be living
(bacteria, fungi) or non- living ( cholesterol, keratin etc)
Commonly found in Immune granulomas & granulomatous
inflammation e.g.- Tubercle Bacillus
Induced by interferon gamma
Positive for CD 68
Large the size and more number of nuclei in MGC’s denotes
increase in disease virulence

44. Langhan’s giant cells in which nucleus is arranged around periphery in the form of
clusters, horse shoe or ring

45. TOUTON’S GIANT CELLS
Originally known as Xanthelasmatic giant cells & are formed by
the fusion of macrophage derived foam cells
Fused foam cells with ring like, wreath shaped arrangement of
nuclei
Peripheral cytoplasm has a foamy & vacuolated appearance &
nuclei surrounds a central area of clear Eosinophilic cytoplasm
Multinucleated cells with vacuolated cytoplasm due to lipid
content
Commonly found in lesions containing cholesterol and lipid
deposits
Associated with Xanthoma, Xanthogranuloma, Fibrous
Histiocytoma
Marker for differenciation – Lysozymes,α-1 antitrypsin,CD68 &
Factor XIIIa

46. Toutan’s Giant cells

47. TUMOR GIANT CELLS
Large tumor cells with single huge polymorphic nucleus or with
two or more nuclei
Nuclei are hyperchromatic & large as compared to size of the
cell and there formation is related to degree of anaplasia of
tumors
Present in many epithelial & mesenchymal Neoplasms
Tumors release extracellular enzymes which reduces the
surface coat thickness & cause approximation of lipid bilayers
leading to fusion
Neoplastic giant cells shows positive for Mindbomb homolog 1
(M1B1) but not for Tartarte Resistant Acid Phosphatase(TRAP)

49. REED- STERNBERG CELLS
Reed- Sternberg cells ( lacunar histiocytes) are found in
Hodgkin’s Lymphoma which occurs due to EBV
Derived from B- Lymphocytes
Typically Binucleated(owl eye nuclei) or multinucleated(
Pennies on a plate) with prominent nucleoli
Positive for CD15/CD30 & negative for CD45/CD20

50. REED STERNBERG CELL WITH OWL EYED NUCLEUS

52. Tuberculous lesions of oral cavity may be primary or secondary
to pulmonary tuberculosis
Primary tuberculosis occurs in previously unexposed people and
mostly
involves the lungs where as secondary tuberculosis occurs from a
reactivation of organism in a previously infected person, typically
associated with compromised host defenses
Tuberculosis (TB) is a specific infectious granulomatous disease
caused by Mycobacterium tuberculosis
ORAL TUBERCULOSIS

53. Tongue is the commonest site for oral Tuberculous lesions, they may also
occur on gingiva, floor of mouth, palate, lips and buccal Mucosa.
Typical oral lesions consists of a stellate ulcer with undermined edges &
a granulating floor
Histopathologic appearance is due to cell- mediated hypersensitivity
reaction.
Formation of granuloma exhibiting foci of caseous necrosis surrounded
by epithelioid cells, lymphocytes, and occasional multinucleated giant
cells are seen.
Langhans’ giant cells are seen, the presence of which is not diagnostic
but
indicative of tuberculosis.
The diagnosis of tuberculosis is confirmed by the presence of acid fast
bacilli in the specimen or culture of sputum

55. Leprosy is a chronic multi-systemic disease caused by acid fast, rod
shaped
bacilli Mycobacterium leprae.
Hard palate is the most frequent site of oral involvement, followed
by soft palate, labial maxillary gingiva, tongue, lips, and buccal mucosa.
Specific lesions like papules, nodules and ulcers shows bacillary
positivity
Involvement of lip may result into cheilitis granulomatosa.
Gingival hyperplasia with loosening of teeth is also seen .
The typical granulomatous nodule shows collections of epithelioid
histiocytes and lymphocytes in a fibrous stroma.
Langhans’ type of giant cells are present
ORAL LEPROSY

57. ORAL ACTINOMYCOSIS
Actinomycosis is a chronic suppurative soft-tissue infection caused by
Actinomyces israelii, which are filamentous, gram-positive, non acid-fast,
anaerobic to microaerophilic bacteria.
Cervicofacial Actinomycosis affects the areas of prior trauma, due to soft
tissue injury, periodontal pocket, non vital tooth, extraction socket or
infected tonsil.
Histopathologically-
A central abscess formation with colonies of microorganisms floating in
a sea of polymorphonuclear Leukocytes & associated with
multinucleated giant cells and macrophages.

58. ORAL SARCOIDOSIS
Sarcoidosis is a systemic non caseating granulomatous disease of
unknown etiology.
The most common presentation consists of pulmonary infiltration and
hilar
lymphadenopathy; dermal and ocular lesions.
Histopathology of sarcoidosis will show non caseating granulomas, the
center of
which usually contains epithelioid macrophages surrounded by a rim of
lymphocytes.
Langhans type giant cells resulting from the fusion of epithelioid
mononuclear cells, occasionally containing many inclusion bodies such
as Schaumann
bodies or stellate asteroid bodies are formed
.

59. FBGC in sarcoidosis

60. Central Giant cell granuloma
Central giant cell granuloma (CGCG) ,(WHO ,2005)-
A rarely aggressive idiopathic benign Intraosseous lesion that occurs
almost exclusively in the jaws.
Most lesions are asymptomatic while minority of cases present with pain,
paraesthesia, or perforation of cortical plate resulting in ulceration of
mucosal
surface.
Histopathologically, CGCG shows hemosiderin laden macrophages and
extravasated erythrocytes
Multinucleated giant cells are present throughout the connective tissue
stroma.
The giant cells contain up to 30 nuclei.
Foci of Osteoid may be present, particularly around the peripheral
margins of lesion

62. PERIPHERAL GIANT CELL
GRANULOMA
Response to local irritation such as tooth extraction, poor dental
restorations, ill fitting dentures, plaque, calculus, food impaction and
chronic trauma.
Histopathologically, fibroblasts are the basic element of peripheral giant cell
granulomas.
Other features include a nonencapsulated highly cellular mass with
abundant giant cells, inflammation interstitial hemorrhage, hemosiderin
deposits, mature bone or Osteoid.
Scattered among the plump, young fibroblasts are numerous
multinucleated giant cells with abundant.
Eosinophilic cytoplasm which appear to be non-functional in the usual
sense of phagocytosis and bone resorption
Originates from the periosteum or periodontal membrane.
It is not a true neoplasm but rather a benign hyperplasic reactive
lesion occurring in-

64. GIANT CELL TUMOR OF BONE
Giant cell tumors (GCTs) are benign bone tumors arising from bone
marrow,
Radiologically, it is usually lytic and expansile without prominent peripheral
sclerosis and periosteal reaction.
The histopathology of GCTs is characterized by frank and marked
haemorrhage, numerous giant cells and stromal cells.
The haemorrhage gives rise to the characteristic grossly lytic picture.
The giant cells are considered reactive while stromal cells are considered
“true” Neoplastic cells.
The giant cells are thought to be originating from circulating monocytes
which then transform into osteoclasts.

66. GIANT CELL FIBROMA
A Rare fibrous hyperplastic lesion that is considered to occur due to
chronic
irritation.
Characterized by functional changes in the fibroblastic cells.
Giant cell fibroma occurs as an asymptomatic sessile or pedunculated
nodule, usually less than 1 cm in size affecting mandibular gingiva.
Histopathologically, the lesions are characterized by a diffuse, somewhat
immature, rather avascular collagenic stroma with small bipolar and slightly
stellate fibroblasts with more then one nucleus.
GCF is characterized by the presence of numerous large stellate and
multinucleated giant cells in a loose collagenous stroma.
The giant fibroblasts are negative for CD68 but show positivity for
vimentin60.

68. GIANT CELL ANGIOFIBROMA
A distinctive benign, mesenchymal tumor commonly encountered in the
orbit
It presents as a slow growing nodule or mass with normal overlying
mucosa.
Histopathologically, is characterized by a richly vascularized, patternless
spindle-cell proliferation containing pseudovascular spaces.
Multinucleated giant cells (often of floret type) and cells with large, rounded
nuclei are present both in the cellular areas and also lining the
pseudovascular spaces.
The stroma is variably collagenized or sometimes myxoid.
Immunohistochemically, the spindle and giant cells are positive for both
vimentin
and CD34.

69. Floret type multinucleated giant cells in giant cell
angiofibroma

70. HODGKIN’S LYMPHOMA
ORAL LESIONS includes: palate, tonsil, floor of mouth, buccal alveolar
mucosa, buccal vestibule, and mandibular bone.
Clinical presentations are ulcerations and swellings.
For the diagnosis of Hodgkin’s lymphoma the presence of Reed Sternberg
cells must be established.
This cell of lymphocytic origin is characterized by its large size and bilobed
nucleus; each containing a large amphophilic or Eosinophilic nucleolus.
The nuclear chromatin pattern is vesicular and condensed at the periphery.
Reed Sternberg cells may be lacunar, polyploid or pleomorphic
Hodgkin’s lymphoma is a malignant Lymphoproliferative disorder which
affects
primarily lymph nodes with secondary extra nodal spread.

72. ANEURYSMAL BONE CYST
Aneurysmal bone cysts are nonneoplastic benign bony lesions with
multilocular appearance.
In the jaw, these manifest as a swelling which develops rapidly.
Pain is present ; paraesthesia, compressibility, and crepitus are rare
Microscopically, numerous cavernous, sinusoidal spaces filled with blood are
surrounded by loose, fibrous connective tissue.
The connective tissue septa contain small capillaries, multinucleated giant
cells, inflammatory cells, extravasated erythrocytes, and hemosiderin.
The multinucleated, osteoclast-like giant cells often aggregate adjacent to
the sinusoidal spaces.
Giant cells were positive for TRAP and Osteoprotegrein, indicative of
osteoclast
phenotype.

75. Large cells that often contain more than one nucleus and appear as a merger
of several distinct cells.
Derived from multiple lineages, but are usually of monocyte or macrophage
origin.
Seen in either in physiologic or in pathologic conditions.
Osteoclasts in the bones, Trophoblast in placenta, Megakaryocytes in the
bone
marrow are the physiologically present multinucleated giant cells.
Common pathological states such as chronic inflammation macrophages fuse
together and form multinucleated giant cells.

76. Multinucleated giant cells can be classified into several morphological
variants depending on the arrangement and composition of their organelles,
as well as their functional characteristics.
These variants include FBGC, Langhans giant cells, Touton giant cells,
osteoclasts and Osteoclast- like cells.
The giant cell lesions of oral cavity have been classified on the basis of
etio- pathogenesis, the presence of which at times being pathognomic like in
Hodgkin’s disease, peripheral giant cell granuloma and giant cell fibroma.
There are conditions like tuberculosis, herpes simplex virus Infection,
measeles and xanthomas where giant cells are characteristic but not
pathognomic.
Diseases like orofacial granulomatosis, fungal infections, fibrous dysplasia
cherubism, Paget’s disease of bone are also associated with the presence
of giant cells.

77. Clinically, Chattopadhyay, et al. (1995) classifies giant cell lesion
according to origin is the most accepted and followed classification.
Pathologically, Rosenberg, et al. (2001) is the most accepted and
followed classification.
Multinucleated giant cells are commonly encountered in various
lesions of oral cavity.
These giant cell containing lesions have overlapping histopathological
features which need to be differentiated from each other.
Accurate identification and categorization of these lesions based on
nature, distribution and origin of giant cells is necessary.
Hence, characterization of giant cells in any giant cell lesion is
essential to assist the clinician and researchers for precise diagnosis
and management