GIANT CELL LESIONS.pptx

GIANT CELL LESIONS
BY DR SUNITA PATHAK

CONTENTS
• INTRODUCTION
• GIANT CELLS
• FORMATION
• TYPES OF GIANT CELLS
• INTRODUCTION
• GIANT CELL LESIONS
• CONCLUSION
• REFERENCES

INTRODUCTION
• A giant cell is a cell that is larger in dimension than the cells
that are routinely encountered in histology.
• These cells are involved in many physiologic and pathological
processes.
• May be mononucleated or multinucleated which can be
explained by the mechanism of their formation.
• Easily recognized under light microscopy and hence provide a
vital clue in arriving to a diagnosis.
• Essential to know the histogenesis of these unique cells, as
the presence of giant cell can have a major implication on the
disease process.

• A multinucleated giant cell (MGCs) is a mass formed by the
union of several distinct cells.
• Usually of monocyte or macrophage lineage.
• Physiologically present multinucleated giant cells.
- Osteoclasts in the bones,
- Trophoblasts in placenta,
- Megakaryocytes in the bone marrow.

• In chronic inflammation when macrophages fail to deal with
particles that has to be removed; fuse together and form
multinucleated giant cells.
• Their role in elimination of foreign substances, damaged
tissue, and pathogens is essential for host survival.
• These cells are able to sequester irremovable materials or
persistent pathogens and prevent further spread of infection.

• Monocyte/macrophages are phagocytic leukocytes that play a
multitude of functional roles in the body and represent key
players in both innate and acquired immune systems.
• Fusion of macrophages can result in the formation of
osteoclasts or a variety of different MGCs.
• Giant cells showing variations in their morphology and
functional patterns are observed in various oral lesions.
• Hence it is important to know the pathogenesis of these
lesions with regards to the role played by the giant cells in
them.

FORMATION
• Multinucleated giant cells were first reported in tuberculous
granulomas by Rokitansky and Langhans, over a century ago.
• Cells of monocyte /macrophage lineage are capable of fusion
to form MGCs.
• These types of cells differ markedly in their association with
disease states, location & prevalence in various tissues or
organs; stimuli that induce the formation of the respective
MGCs, and subsequent function of these cells.

• Giant cells are found in-
• Granulomas associated with the immune response to
tuberculosis, leprosy, syphilis,
• Various fungal and parasitic infections
• Non-immune responses
- Toxic agents such as silica, beryllium, and asbestos;
- Non-toxic agents such as carbon particles, plastic beads, and
iron particles.

• Since a variety of agents produce granulomas, it is thought
that the giant cells are produced by different mechanisms.
• The two theories that were considered are:
1. Amitotic division of monocyte nuclei in the absence of
cellular division.
2. Fusion of non replicating monocytes.

• Auto-radiographic studies have revealed that giant cells
indeed form due to fusion, which has been supported by
other authors also.
• Cell fusion results from an alteration of cell surface which
allows close membrane approximation, followed by
establishment of continuity between the apposed lipid
bilayers.

• The process of fusion can occur due to a variety of
mechanisms.
• Firstly, an immune mediated phenomenon has been proposed
for the formation of giant cell.
• Here large amount of lymphokines are produced that causes
fusion of macrophages to form multinucleated giant cells.
• Macrophage MGCs are commonly found in areas containing
poorly removable foreign material which are antigenic
(microorganisms).
• Even when the foreign material itself has no antigenicity (Eg:
Glass) it is possible that the inflammatory process itself
produces antigen which is responsible for macrophage fusion.

• Secondly, it was also proposed that fusion occurs between
"young“ macrophages and "older" cells, the latter having
existed for some time in the granulomatous environment
acquiring chromosomal abnormalities and changes on
macrophage surface.
• Recognition of altered and abnormal cell surface by young
macrophages is the stimulus for cell fusion.
• Third mechanism proposed, suggested that when two or
more macrophages try to ingest the same particle, there is
simultaneous attempted phagocytosis resulting in the fusion
of endosomal margins to form multinucleated giant cells.

• The role of viruses in fusion of many cell types throughout the
body, including macrophages has been explained.
• Fusion may be achieved by large doses of inactivated virus or
by much smaller doses of infective virus.
• With inactivated virus there appears to be a direct interaction
between the viral envelope and cell surface.
• Attachment of viral envelope leads to the reduction in cell
coat thickness and fusion with the cell membrane.

• Cell fusion results if the virus is in contact with more than one
cell.
• Antigens from the viral envelope become incorporated into
the polykaryon membrane, resulting in the fusion between
the two cells by forming a "bridge".
• Live virus penetrates a cell and leads to fusion following the
appearance of virally coded proteins on the cell surface.
• The infected cell thus has a surface modified by viral proteins
which leads to fusion with adjacent uninfected cells.
• Fusion extends in a plaque to form an expanding syncytium.

TYPES OF GIANT CELLS
• Multinucleated giant cells can be classified into several
morphological variants
- Depending on the arrangement and composition of their
organelles.
- Functional characteristics.
• Osteoclasts, odontoclasts, skeletal muscle fibers,
syncytotrophoblasts and megakaryocytes are the
physiologically present multinucleated giant cells.
• Few of these also have a role to play in various pathological
processes.

OSTEOCLASTS
• Named by Kolliker are bone-resorbing cells that play a pivotal
role in bone homeostasis and remodeling.
• Osteoclast precursors are derived from bone marrow as early
mononuclear macrophages, which circulate in blood, and bind
to the surface of bone.
• Osteoclast formation is driven mainly by two cytokines,
Receptor Activator of Nuclear Factor Kappa β Ligand (RANKL)
and macrophage - colony stimulating factor (M-CSF).
• Factors like systemic hormones and growth factors influence
the formation and function of osteoclasts.

• Morphologically, osteoclasts are similar to foreign body giant
cells, although they have considerably fewer nuclei.
• Usually contain 10 to 20 nuclei per cell and are found on bone
surfaces;
• On the endosteal surfaces within the haversian system;
• On the periosteal surface beneath the periosteum.

• The osteoclastic giant cells show positivity to cathepsin K,
alkaline phosphatase, RANKL, osteoprotegerin & Cluster of
Differentiation 68 (CD68).
• Calcitonin receptor is found to be a more specific marker of
differentiation for osteoclasts from other giant cells derived
from monocyte/ macrophage cell lineage.

SYNCYTIOTROPHOBLASTS IN PLACENTA
• Trophoblasts (from Greek trephein
: to feed, and blastos: germinator).
• Cells form the outer layer of a
blastocyst, which provide nutrients
to the embryo and develop into a
large part of the placenta.
• They are formed during the first
stage of pregnancy and are the
first cells to differentiate from
the fertilized egg.

• Trophoblasts are specialized cells of the placenta that play an
important role in embryo implantation and interaction with
the maternal uterus.
• The core of placental villi contain mesenchymal cells and
placental blood vessels that are directly connected to the fetal
circulation via the umbilical cord.
• This core is surrounded by two layers of trophoblast; a single
layer of mononuclear cytotrophoblast that fuse together to
form the overlying multinucleated syncytiotrophoblast layer
that covers the entire surface of the placenta.

• Cytotrophoblast- inner layer single
celled, inner layer of the
trophoblast.
• Syncytiotrophoblast- outer thick
layer that lacks cell boundaries and
grows into the endometrial stroma.
• It secretes hCG in order to
maintain progesterone secretion
and sustain a pregnancy.
• It is in direct contact with the
maternal blood that reaches the
placental surface, and thus
facilitates the exchange of nutrients,
wastes and gases between the
maternal and fetal systems.

MEGAKARYOCYTES
• Megakaryocyte (mega + karyo + cyte
"large-nucleus cell") is a large bone
marrow cell with a lobulated
nucleus.
• Responsible for the production of
blood thrombocytes (platelets),
which are necessary for normal
blood clotting.
• Normally account for 1 out of
10,000 bone marrow cells but can
increase in number nearly 10-fold
during the course of certain
diseases.

• Megakaryocytes are 10 to 15 times
larger than a typical red blood cell,
averaging 50-100 μm in diameter.
• During its maturation, it grows in size
and replicates its DNA
without cytokinesis in a process
called endomitosis.
• As a result, the nucleus of the
megakaryocyte can become very large
and lobulated, which, under a light
microscope, can give the false
impression that there are several nuclei.
• In some cases, the nucleus may contain
up 32 copies of the normal complement
of DNA in a human cell.

• Megakaryocytes are derived from hematopoietic stem
cell precursor cells in the bone marrow.
• Produced primarily by the liver, kidney, spleen, and bone
marrow.
• These multipotent stem cells live in the marrow sinusoids and
are capable of producing all types of blood cells depending on
the signals they receive.
• The primary signal for megakaryocyte production is
thrombopoietin or TPO.
• Other molecular signals for megakaryocyte differentiation
include GM-CSF, IL-3,IL-6, IL-11, chemokines (SDF-1, FGF-4)
and erythropoietin.

• The megakaryocyte develops through the following lineage:
• Pluripotential hemopoietic stem cell or hemocytoblast -
> megakaryoblast -> promegakaryocyte -> megakaryocyte.
• The cell eventually reaches megakaryocyte stage and loses its
ability to divide.
• Still able to replicate its DNA and continue development,
becoming polypoid.
• The cytoplasm continues to expand and the DNA complement
can increase up to 64N in human.
• Once the cell has completed differentiation and become a
mature megakaryocyte, it begins the process of producing
platelets.

TOUTON GIANT CELLS
• Characterized by multiple
nuclei that cluster together in
the cell and are surrounded by
foamy cytoplasm.
• These cells were originally
known as xanthelasmatic giant
cells and are formed by fusion
of macrophage derived foam
cells.

Touton giant cells are another type of
multinucleated giant cells derived
from macrophages and contain lipid.
They are found in xanthoma,
xanthogranuloma and fat necrosis.
Nuclei are arranged in a wreath like
pattern. Its peripheral cytoplasm has
a foamy or vacuolated appearance
due to lipid and nuclei surrounds
central area of eosinophilic
cytoplasm.

• Frequently found in lesions containing cholesterol and lipid
deposits, and are associated with various pathologic
processes, such as xanthomas and xanthogranulomas.
• Touton types of giant cells are appreciated in cases of fibrous
histiocytoma.
• The lipid droplets in the cytoplasm of these cells can be
demonstrated in frozen section by special stains.
• Lysozyme, α1 antitrypsin, CD68 & factor XIIIa can be used as a
marker for differentiation of these multinucleated giant cells.

LANGHANS GIANT CELLS
• Characterized by the presence
of few nuclei (< 20) arranged
peripherally, within the giant
cell.
• Commonly found in immune
granulomas and granulomatous
inflammations in the presence
of indigestible particles of
organisms, eg: the tubercle
bacillus.

• In Langhans giant cell the
nuclei are disposed to the
periphery of the cell in the
form of a horse shoe.
• These are conspicuous in
lesions of Tuberculosis.

• Presence of MGCs in the tuberculous granuloma was first
described by Langhans in 1868.
• Interferon gamma (IF-γ) plays a central role in inducing
Langhans’ giant cell formation.
• These cells show positivity to CD68.
• It has also been seen that larger the size and more the
number of nuclei in MGCs, the virulence of disease increases.

• Lay et al have shown that
• High virulence mycobacterium, i.e., Mycobacterium
tuberculosis, induces large MGCs with more than 15 nuclei per
cell.
• Low virulence mycobacterium species, Mycobacterium avium
and Mycobacterium smegmatis, have low number of nuclei
per cell, less than seven.
• High-virulence mycobacterium species resulted in granulomas
where the MGCs phagocytic activity was absent.
• Low-virulence species produced MGCs where phagocytic
activity was present.

FOREIGN BODY GIANT CELLS
• Foreign body giant cells
(FBGCs) are generated by
macrophage fusion and
serve the same purpose as
osteoclasts:
degradation/resorption of
the underlying substrate.

.
Foreign-body giant cells are
frequently seen around exogenous
foreign material like catgut, silk, talc,
silica and plastic sponges. They are
also present around endogenous
debris as sequestra, keratin,
cholesterol crystals and uric acid
crystals (in gout).
Nuclei are scattered haphazardly
throughout the cytoplasm and
some are present centrally and in
close clusters.

• Unlike osteoclasts, which adhere to bone, FBGCs adhere to
markedly different synthetic surfaces that display distinct
differences in hydrophilic/hydrophobic character as well as
chemical and physical properties.
• Contain many nuclei (up to 100 - 200) that are arranged in a
diffuse manner throughout the cytoplasm.
• Observed at the tissue-material interface of medical devices
implanted in soft and hard tissue and remain at the implant-
tissue interface for lifetime, of the device in vivo.

ASCHOFF NODULES/BODY
• Aschoff bodies are
nodules found in the hearts of
individuals with rheumatic fever.
• Result from inflammation in
the heart muscle and are
characteristic of rheumatic heart
disease.
• These nodules were discovered
independently by Ludwig
Aschoff and Paul Rudolf Geipel,
and for this reason they are
occasionally called Aschoff-
Geipel bodies.

• Spherpoidal or fusiform distinct
tiny structures, 1-2mm in size,
occurring in the interstitium of
the heart.
• Fully developed Aschoff bodies
are granulomatous structures
consisting of fibrinoid change,
lymphocytic infiltration,
occasional plasma cells, and
characteristically abnormal
macrophages surrounding
necrotic centres.
• Some of these macrophages
may fuse to form
multinucleated giant cells

• They are pathognomic foci of fibrinoid necrosis found in many
sites, most often the myocardium.
• Initially they are surrounded by lymphocytes, macrophages,
and a few plasma cells, but they are slowly replaced by a
fibrous scar.
• They are especially found in the vicinity of small blood vessels
in the myocardium and endocardium and occasionally in the
pericardium.

TUMOR GIANT CELLS
• Many epithelial and mesenchymal neoplasms contain tumor
giant cells.
• Nuclei of these giant cells are pleomorphic, often diploid,
shows abnormal mitosis and resemble those of mononuclear
tumor population.
• Tumor cells are known to possess an abnormal surface and
are predisposed to fusion in different ways.
• Release extracellular enzymes which may reduce the surface
coat thickness and cause close approximation of lipid bilayers
leading to fusion.
• Some tumors have been found to be associated with
passenger viruses, which are known to cause cell fusion.

Classic Reed-Sternberg cell
– Large, binucleate or bilobed, with
the two halves often appearing
as “mirror-image” of each other.
– Nucleus: may be multiple or
multilobate, contains large,
inclusion-like, owl-eyed nucleoli,
generally surrounded by a clear
halo, that are about the size of a
small lymphocyte .
– Cytoplasm: abundant
amphophilic.

• 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.
• Reed–Sternberg cells are CD30 and CD15 positive, usually
negative for CD20 and CD45.

GIANT CELL LESIONS OF ORAL CAVITY
• Giant cell lesions of oral cavity can be cystic, neoplastic,
microbial, etc.
• For proper diagnosis and management of giant cell lesions, it
is necessary to know about the pathogenesis of disease and
the nature of giant cells.
• Giant cell lesions of oral cavity have been classified based on
the etiopathogenesis as described by Chattopadhyay A (1995)
and Varghese et al.

Classification
1. Microbial lesions
a. Tuberculosis
b. Leprosy
c. Actinomycosis
d. Sarcoidiosis
2. Tumor and tumor like lesion
a. Central giant cell granuloma
b. Peripheral giant cell granuloma
c. Giant cell fibroma
d. Osteosarcoma
e. Rhabdomyosarcoma
f. Hodgkins lymphoma
3. Cystic lesion
a. Traumatic bone cyst
b. Aneurysmal bone cyst
4. Metabolic lesion
a. Hyperparathyroidism
5. Osteodystrophic lesion
a. Noonan-like multiple giant cell
lesion syndrome
6. Miscellaneous lesion
a. Cherubism
b. Paget’s disease
c. Fibrous dysplasia
Varghese I, Prakash A. Giant cell lesion of oral cavity. OMPJ 2011;2:976-1225.

Classification of giant cell lesions of oral cavity based on the
pathogenesis.
Lesions where giant
cells in
the concerned
background
are pathognomic
Hodgkins lymphoma
Peripheral/central
giant cell
granuloma
Giant cell fibroma
Lesions where giant
cells are characteristic
but not pathognomic
Tuberculosis
Herpes Simplex Virus
infection
Measles
Xanthoma
Lesions associated with
presence of giant cell
Orofacial granulomatosis, fungal
infection, foreign body reaction,
neoplasm, syphilis, leprosy,
fibrous dysplasia, cherubism,
ossifying fibroma, aneurysmal
bone cyst, paget’s disease of
bone, wegners granulomatosis
actinomycosis, odontogenic giant
cell fibromatosis
Chattopadhyay A. Giant cells and giant cell lesions of the oral cavity. Journal of
Indian Dental Association. 1995;66 (11):326-327.

Oral Tuberculosis
• Tuberculosis (TB) is a specific infectious granulomatous
disease caused by Mycobacterium tuberculosis.
• 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.
• Secondary tuberculosis occurs from a reactivation of organism
in a previously infected person, typically associated with
compromised host defenses.

TB Invades/Infects the Lung
TB: Airborne Transmission

• 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 consist of a stellate ulcer with undermined
edges and a granulating floor.
• The characteristic histopathologic appearance is due to cell-
mediated hypersensitivity reaction.

• Formation of granuloma
exhibiting foci of caseous
necrosis surrounded by
epitheloid 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.

• Typical tuberculous
granuloma showing an area
of central necrosis
surrounded by multiple
Langhans-type giant cells,
epithelioid cells, and
lymphocytes.
• In Langhans giant cell the
nuclei are disposed to the
periphery of the cell in the
form of a horse shoe. These
are conspicuous in lesions
of Tuberculosis.

• Diagnosis of tuberculosis is
confirmed by the presence of
acid fast bacilli in the specimen
or culture of sputum.
The acid-fast bacteria mycobacteria appear
bright red following Ziehl-Neelsen staining.

Acid-Fast (Kinyoun) Stain of Mycobacterium
NOTE: cord growth (serpentine arrangement) of
virulent strains

Eight Week Growth of Mycobacterium tuberculosis on
Lowenstein-Jensen Agar

Mycobacterium Tuberculosis Stained with Fluorescent Dye

 Pneumonia
 Granuloma formation with fibrosis
 Caseous necrosis
• Tissue becomes dry & amorphous (resembling cheese)
• Mixture of protein & fat (assimilated very slowly)
 Calcification
• Ca++ salts deposited
 Cavity formation
• Center liquefies & empties into bronchi
Typical Progression of Pulmonary
Tuberculosis

Chest X-Ray of Patient with Active Pulmonary
Tuberculosis
Postero-anterior chest
radiograph showing
bilateral upper lobe
consolidation and
cavitation, consistent
with pulmonary
tuberculosis.

Oral leprosy
• Leprosy is a chronic multi-systemic disease caused by acid
fast, rod shaped bacilli Mycobacterium leprae.
• It is mainly a Granulomatous disease affecting: peripheral
nerves and mucosa of the upper-respiratory tract.
• Clinico-pathological presentation is determined by the
complex interaction between the invading organism and
immune status of the individual.

• The transmission of leprosy is thought to occur through the
respiratory tract.
• Infected individuals discharge bacilli through their nose and a
healthy individual breaths them in.
 Nasal/oral Droplets
 Dermal Inoculations

• Hard palate is the most frequent site of oral involvement,
followed by soft palate, labial maxillary gingiva, tongue, lips,
and buccal mucosa.
• Spectrum of oral lesions may vary from papules, nodules and
ulcers showing bacillary positivity.
• Involvement of lip may result into cheilitis granulomatosa.
• Gingival hyperplasia with loosening of teeth has also been
reported.

Signs of leprosy
• Pale or slightly reddish patch
• Definite loss of sensation in the patch
• Signs of damage to nerves
– definite loss of sensation in hands/feet
– weakness of muscles of hands/feet/face
– visible deformity of hands/feet/face
 Diagnosis is clinical, by finding signs of leprosy and
supported with the use of acid-fast bacilli smear or skin
biopsy

Symptoms & Diagnosis:
(2) Skin Smear Tests
Ziehl Neelsen Carbol Fuchsin Stain (ZNCF)

• The typical granulomatous
nodule shows collections of
epitheloid histiocytes and
lymphocytes in a fibrous
stroma.
• Langhans’ type giant cells
are variably present.
First line drugs are rifampicin, dapsone, and clofazimine and
Second line drugs are ofloxacin and minocycline. (6-24 months)

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
that live as commensal organisms in the oral cavity,
respiratory and digestive tracts.
• Clinical manifestations of actinomycosis occur in three areas:
- Cervicofacial (50%),
- Abdominal-pelvic (23%),
- Thoracic (17%).

• Suppurative reaction of the infection may discharge large
yellowish flecks that represent colonies of bacteria called
sulphur granules.
• Cervicofacial actinomycosis affects the areas of prior trauma,
due to soft tissue injury, periodontal pocket, non vital tooth,
extraction socket or infected tonsil.

HISTOPATHOLOGY
• Central abscess formation
with colonies of
microorganisms floating in a
sea of polymorphonuclear
leukocytes is observed.
• Often associated with
and macrophages
particularly around the
periphery of the lesion.

• Actinomycosis. This single,
complete loculus is from an early
case of actinomycosis.
• The colony of actinomyces with
its paler staining periphery (a
'sulphur' granule) is in the centre;
around it is a dense collection of
inflammatory cells, surrounded in
turn by proliferating fibrous
tissue.

• The diagnosis is usually made by fine-needle aspiration biopsy
followed by observing actinomycosis colonies or sulfur
granules in microscopic examination.

Oral Sarcoidosis
• Sarcoidosis, in Greek meaning “flesh like condition” is a
systemic non caseating granulomatous disease of unknown
etiology.
• Genetic, infectious and environmental factors have been
postulated as possible cause.
• Most common presentation consists of pulmonary infiltration
and hilar lymphadenopathy; dermal and ocular lesions.
• When the parotid glands are affected, 4-6% of cases present
as parotitis and Heerfordt syndrome.

.
• Histopathology of sarcoidosis will
show non caseating granulomas,
the center of which usually
contains epitheloid macrophages
surrounded by a rim of
lymphocytes.
• Langhans type giant cells resulting
from the fusion of epitheloid
mononuclear cells, occasionally
containing many inclusion bodies
such as Schaumann bodies or
stellate asteroid bodies are
observed.
• Non-caseating granuloma of
sarcoidosis (giant cell
indicated).

• Corticosteoids have remained as the mainstay in treatment of
sarcoidosis although with a chance of around 70% relapse
within a two years period.

Asteroid bodies (ABs):
• ABs are striking cytoplasmic inclusions in giant cells of
granulomas of many types including those of sarcoidosis,
tuberculosis, leprosy, fungal infections, schistosomiasis, and
lipoid and foreign body types.
• Vary in size from 5 to 30 µm and have up to 30 rays forming a
star-like, spider, or umbrella pattern.
• The surrounding cytoplasm is vacuolated.
• Pathophysiologic changes that produce the ABs are unknown.
• Ultrastructural findings: The fibrillar material of the spokes
radiates from a granular center.
• The vacuoles between the spokes contain lamellated, lipoidal,
myelin figures that may be related to the formation of
Schaumann bodies.

• Two multinucleated giant cells
shown here has an asteroid
body with surrounding
vacuoles in the cytoplasm.
• The basophilic body in the
giant cell to the left may be an
early, small Schaumann body.
• As with Schaumann bodies,
the ABs are found in the non-
necrotizing granulomas and
not in necrotic areas.

Central giant cell granuloma
• Classified by the World Health Organization in 2005 as a rarely
aggressive idiopathic benign intraosseous lesion that occurs
almost exclusively in the jaws.
• Most lesions are asymptomatic.
• Minority of cases present with pain, paraesthesia, or
perforation of cortical plate resulting in ulceration of mucosal
surface.

Radiology shows a well demarcated and in places corticated
radiolucency. Lesions may be large and often displace the adjacent
teeth

HISTOPATHOLOGY
• CGCG shows hemosiderin laden
macrophages and extravasated
erythrocytes along with small
inconspicuous capillaries.
• Multinucleated giant cells are
present throughout the connective
tissue stroma, and may be seen in
patches or evenly distributed around
areas of haemorrhage. The giant cells
contain up to 30 nuclei.
• Foci of osteoid may be present,
particularly around the peripheral
margins of lesion.

• Accumulations of
embedded in a cellular
stroma composed
predominantly of plump
mononuclear cells.
• These are primarily
osteoblasts and
mononuclear osteoclast
precursors.
• The lesion is vascular with
areas of red cell
extravasation.

Peripheral giant cell granuloma
• PGCG is one of the most frequent giant cell lesion of the jaws
and originates from the periosteum or periodontal
membrane.
• It is not a true neoplasm but rather a benign hyperplastic
reactive lesion occurring in response to local irritation such as
tooth extraction, poor dental restorations, illfitting dentures,
plaque, calculus, food impaction and chronic trauma.

HISTOPATHOLOGY
• 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
with abundant
eosinophilic cytoplasm
which appear to be non-
functional in the usual
sense of phagocytosis and
bone resorption.

• Management of this gingival lesion is surgical excision and
elimination of any local contributing factors.

Giant cell tumor of bone
• Benign bone tumors arising from bone marrow, which account
for about 5% of all biopsied primary bone tumors.
• The head and neck region constitute approximately 2% of all
GCTs, with the majority occurring in sphenoid, ethmoid, or
temporal bones.
• Radiologically, it is usually lytic and expansile without
prominent peripheral sclerosis and periosteal reaction.

Osteoclastoma
Soap bubble appearance
Expanding lytic lesion surrounded by a
thin rim of bone
It may have a soap-bubble appearance

HISTOPATHOLOGY
• 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.
• Treatment includes simple or aggressive curettage.
• Tumor resection and reconstruction with prosthesis or a large
segment allograft has a low rate of local recurrence.

Difference between Giant cell granuloma and
Giant cell tumour
CENTRAL GIANT CELL GRANULOMA GIANT CELL TUMOUR
Reactive lesion Neoplastic lesion
Generally occur in younger subjects
Hemorrhagic background Absence of hemorrhage
Presence of plump bland fibroblasts & presence of
large areas of fibrosis,
Absence of fibroblasts
Haemosiderin
Fewer giant cells. Diffuse sheets of large giant cells and polygonal
mononuclear cells seen
Giant cells with smaller number of nuclei Giant cells with larger number of nuclei
Giant cells are less uniformly distributed Uniformly scattered
Deposition of osteoid is occasionally observed Lacking
Higher proliferative activity Less

CENTRAL GIANT CELL GRANULOMA GIANT CELL TUMOUR
young patients Older patients
predilection for females Males
anterior part of the mandible articular end of tubular bones
unilocular or a multilocular radiolucent
lesion
entirely lytic and expansile lesion in the
epiphysis, usually without peripheral
bone sclerosis or periosteal reaction
Histologically, the tumor consists of
a moderately vascularized network of
stromal cells and multinucleated giant
cells meagerly interspersed with
collagenous fibrils. The stromal cells are
mononuclear and in general resemble
young connective tissue cells. They are
spindle shaped or ovoid in varying
Proportions.
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.

• Both diseases showed similar cellular phenotype in respect of
Vimentin, S100 protein, CD68 and CD34.
• There is increased immunoreactivity of GCT to Ki-67, P53 and
αSMA.

Giant cell fibroma
• GCF is a relatively rare fibrous hyperplastic lesion that is
considered to occur due to chronic irritation.
• Characterized by functional changes in the fibroblastic cells.
• Occurs as an asymptomatic sessile or pedunculated nodule,
usually less than 1 cm in size affecting mandibular gingiva
twice as common as maxillary.

HISTOPATHOLOGY
• GCF are characterized by a
diffuse, somewhat immature,
rather avascular collagenic
stroma with small bipolar and
slightly stellate fibroblasts
scattered throughout in
moderate numbers.
• Occasional fibroblasts will be
quite large and angular, and
may have more than 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 vimentin.

Giant cell angiofibroma
• GCA is a distinctive benign, mesenchymal tumor commonly
encountered in the orbit.
• Occur in submandibular region, parascapular area, posterior
mediastinum and in the oral cavity.
• Presents as a slow growing nodule or mass with normal
overlying mucosa.

HISTOPATHOLOGY
• GCA 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.

OSTEOSARCOMA
• Most common primary malignant tumor of bone
• Clinically:
– Males> females
– Most occur in teenagers (age 10-25 years)
– Localized pain and swelling
 Osteosarcoma is an aggressive malignant neoplasm arising
from primitive transformed cells of mesenchymal origin
that exhibit osteoblastic differentiation and produce
malignant osteoid.

• Classic X-ray findings:
1. Codman's triangle (periosteal elevation)
2. Sunburst pattern
3. Bone destruction
• Pathology:
– Often involves the metaphysis of long bones
– Usually around the knee (distal femur and proximal tibia)
– Large firm white tan mass with necrosis and haemorrhage

• Codman triangle is a term
used to describe the
triangular area of new
subperiosteal bone that is
created when a lesion, often
a tumour, raises the
periosteum away from the
bone.
• Sun-burst" appearance on X-
ray examination due to the
tumor spicules of calcified
bone radiating in right angles

Codman's triangle
Osteosarcoma

HISTOPATHOLOGY
• Osteosarcoma is formed of
Spindle shaped cells
showing malignant criteria
in form of pleomorphism,
hyperchromasia, abnormal
mitosis, giant cells .

Osteoid
Deposition
In between spindle cells there is malignant osteoid.

RHABDOMYOSARCOMA
• Embryonal Rhabdomyosarcoma :
• Usually occurs in children (before the age of 10 years).
• Common sites include head and neck region, genitourinary
tract and retroperitoneum.

HISTOPATHOLOGY
• Alternating cellular and myxoid areas.
• Classical form is composed of
undifferentiated round or spindle cells
together with a few scattered
eosinophilic rhabdomyoblasts.
• Some elongated rhabdomyoblasts show
angulation of muscle fibres (broken
straw sign).
• Multivacuolated or spider web cells
may be present.
• Cytoplasmic cross striations are noted
in about 20-30% cases.
• Intracellular glycogen is more
prominent in well-differentiated forms.

• Immunohistochemistry plays an important role in establishing
the diagnosis.
• Desmin and muscle actin are positive.
• MyoD1 and myogenin (myf4) are also useful markers.
• Variants:
1) Botryoid
2) Spindle cell
3) Anaplastic

Hodgkin’s lymphoma
• Malignant lymphoproliferative disorder which affects
primarily lymph nodes with secondary extranodal spread.
• Presents as cervical lymphadenopathy and rarely involves
extranodal sites.
• Palate, tonsil, floor of mouth, buccal alveolar mucosa, buccal
vestibule, and mandibular bone, with no one site accounting
for a predominance of cases.
• Commonly described clinical presentations are ulcerations
and swellings.

HODGKIN LYMPHOMA—LYMPH
NODE.
• A binucleate Reed-Sternberg cell
with large, inclusion-like nucleoli
and abundant cytoplasm is
surrounded by lymphocytes,
macrophages, and an eosinophil.
HODGKIN LYMPHOMA, NODULAR
SCLEROSIS TYPE—LYMPH NODE.
• A distinctive "lacunar cell" with a
multilobed nucleus containing many
small nucleoli is seen lying within a
clear space created by retraction of its
cytoplasm.
• It is surrounded by lymphocytes.

• Treatment includes cytotoxic drugs, immunotherapy and
radiotherapy.
• High dose chemotherapy and autologous stem cell
transplantation has also become an established mode of
treatment.
• The prognosis of the disease can be related to the number of
giant cells.
• Lymphocyte depletion type of Hodgkin’s lymphoma which has
the most abundant Reed Sternberg cells shows the least
favorable prognosis.

Traumatic Bone Cyst
• Pseudocyst (lacks an epithelial lining)
• Uncommon lesion , comprises of 1 % of all jaw cysts.
• Etiology is unknown.
• Trauma hemorrhage theory most accepted.
• Hemorrhage occurring within the medullary spaces of bone leads to
clot formation which breaks down and leaves an empty cavity
within the bone.
• Steady expansion of the lesion occurs , secondary to altered or
obstructed lymphatic or venous drainage.
• This expansion cease when the cyst like lesion reaches the cortical
layer of bone and expansion is not a common finding in solitary
bone cyst.

Other theories of origin:
• Cystic degeneration of primary bone tumours.
• Result of faulty calcium metabolism such as that induced by
parathyroid disease.
• Ischemic necrosis of fatty marrow.
• End result of low grade chronic infection.
• Result of osteoclasis, resulting from a disturbed circulation
caused by trauma creating an unequal balance of osteoclasis
and repair of bone.

CLINICAL FEATURES
• Occurs in young persons
• Second decade of life, mean age- 18 yrs.
• No definite sex predilection, but males more common than
females.
• Mandible > Maxilla
• Posterior> Anterior
• Swelling
• Rarely pain
• Bony cavity may be empty
• May contain sero-sanguinous fluid, shreds of necrotic blood
clot, fragments of necrotic blood clot, fragments of fibrous
connective tissue.

RADIOGRAPHIC FEATURES
• Well-defined (corticated)
radiolucency.
• Variable size- few cm to
several cm involving body
and ramus of mandible
• Cavity may have a lobulated or
scalloped appearance extending
between the roots of the teeth.
• Seldom displacement of teeth.
• Vital teeth

• Traumatic bone cyst usually lies above the mandibular canal.
• Asymptomatic traumatic bone cysts may be detected on
panoramic radiography.

HISTOLOGIC FEATURES
• Thin connective tissue
membrane lining the cavity.
• No such membrane may be
demonstrable.
• Extensive osteophytic
reaction on the outer
surface of cortical plate.
• May be presence of few red
blood cells, blood pigments,
or giant cells adhering to
the surface.

TREATMENT
• Clinically, surgeons report an empty cavity at entrance in
about two thirds of the cases.
• Blood clot is also present occasionally.
• The bony cavity is scraped to generate bleeding, which is
considered the treatment of choice for this condition.
• Other methods of treatment include, packing the curetted
cavity with autogenous blood, autogenous bone and
hydroxyapetite.
• Exploration surgery usually leads to healing.
• Recurrence are rare.

Aneurysmal bone cyst
• Nonneoplastic benign bony lesions with multilocular
appearance.
• When present in the jaw, these manifest as a swelling which
develops rapidly.
• Pain is often reported; paraesthesia, compressibility, and
crepitus are rare.
• According to Hillerup and Hjorting-Hansen, an intra-medullary
haematoma secondary to trauma, may be the causative factor
for the development of ABC.

ANEURYSMAL BONE CYST
• Bone is expanded and
appears cystic.
• Honey comb or soap bubble
appearance and is
eccentrically ballooned.
• Cortical bone may be
destroyed and periosteal
reaction may be evident.

HISTOPATHOLOGY
• Numerous cavernous, sinusoidal
spaces filled with blood are
surrounded by loose, fibrous
connective tissue.
• Connective tissue septa contain
small capillaries, multinucleated
giant cells, inflammatory cells,
extravasated erythrocytes, and
hemosiderin.
• Multinucleated, osteoclast-like
giant cells often aggregate
adjacent to the sinusoidal spaces.

• Various treatment options include percutaneous
sclerotherapy, diagnostic and therapeutic embolization,
curettage, block resection and reconstruction, radiotherapy
and systemic calcitonin therapy.
• Self healing cases have also been reported on long term
follow up.

HYPERPARATHYROIDISM
• Endocrine abnormality in which there is an excess of
circulating parathyroid hormone (PTH).
• The PTH mobilizes calcium from the skeleton and decreases
renal tubular reabsorption of phosphate.
• Primary hyperparathyroidism is caused by a benign tumor or
hyperplasia of the parathyroid gland, producing an excess
quantity of PTH hormone.
• In primary hyperparathyroidism, the serum calcium is
elevated beyond its normal 9-11 mg % range by resorption of
calcium from bones and decreased renal excretion of calcium.
• The serum phosphorus level is decreased.

• Secondary hyperparathyroidism is the result of certain types
of kidney diseases that cause hypocalcemia, thereby
stimulating the parathyroid glands to secrete excess PTH in an
attempt to elevate the serum calcium level.
• The serum calcium is normal to decreased and serum
phosphorus is increased.

Stones, bones, abdominal groans and psychiatric moans
(renal stones, peptic ulcers, pancreatitis, confusion, lethargy, weakness)

• Hyperparathyroidism is a common cause of generalized
rarefaction of the jaws.
• The skeleton undergoes generalized osteoporosis and is seen
on a radiograph as having a ground glass appearance with loss
of trabecular bone pattern.
• In a small percentage of patients there is loss of lamina dura
around all the teeth.
• The lost lamina dura returns after successful treatment of the
disorder.

• Late in the disease, a
small number of cases
develop central giant
cell lesions known as
"brown tumors.“
• These "brown tumors"
appear radiographically
as ill-defined
radiolucencies.
Panoramic radiography showing a multilocular
radiolucency of the right mandible.

• There is a tendency for the patients to develop renal stones.
The serum alkaline phosphatase level is elevated.
• Increase in serum alkaline phosphatase level occurs in
systemic and bone diseases whenever there is significant
bone resorption or turnover.
• Note: "Brown tumors" are histologically identical with the
central giant cell granuloma of the jaws. For this reason,
hyperparathyroidism should always be ruled out in a patient
with a giant cell lesion of the jaws.

Noonan-like/multiple giant cell lesion syndrome
(NL/ MGCLS)
• Clinical similarities with Noonan’s syndrome and cherubism.
• It is unclear whether it is a distinct entity or a variant of
Noonan’s syndrome or cherubism.
• Inheritance- Autosomal dominant or sporadic.
• Head/neck- Giant cell lesions in bone/soft tissue,
Hypertelorism, Prominent, posterior ears, Short webbed neck,
Ptosis, downward palpebral fissures, Epicanthic folds, High
arched palate, Enlarged submandibular lymph nodes,
Bitemporal narrowing.
• Growth- short stature.
• Cardiovascular- pulmonary stenosis and aortic regurgitaton.

• Dermatological- Cafe´ au lait spots, Involuted haemangioma
• Neurological- Developmental delay
• Hematological- Clinically non-significant increase in PT/PTT

PAGET'S DISEASE (Osteitis deformans)
• Disease of unknown etiology.
• Incidence increases in older individuals, especially those over
the age of 40 years.
• Pain in a bone may be mistaken for arthritis.
• Initial lesion is one of destruction by resorption; later an
excessive amount of bone is deposited in a haphazard fashion
with a diminution of vascularity of the lesion.
• New bone is of poor quality and may result in increased bone
fragility and a tendency to fracture.
• Pathologic fracture is one of the most common complications
of Paget's disease.

• Neurologic symptoms in Paget's disease develop gradually
and consist of bone pain, severe headache, deafness, loss of
sight, dizziness, facial paralysis, mental disturbance and
weakness.
• Disease may be monostotic or polyostotic. When polyostotic,
the bones most prominently affected are those of the axial
skeleton which include the skull, vertebral column,
extremities and maxilla.
• Progressive enlargement of the skull, bowing deformity of
long bones and dorsal kyphosis (spinal curvature).
• The patient develops a waddling gait.

• Jaws are involved in only 20% of cases; the maxilla is more
frequently affected than the mandible (3:1 ratio).
• In some instances, both jaws are involved.
• Ultimately the alveolar ridge widens, with a relative flattening
of the palatal vault.
• Enlargement of the maxilla and/or the mandible results in
migration, spacing of the teeth and malocclusion.
• Dentures may have to be remade periodically to
accommodate the increase in jaw size.

• An important diagnostic feature of Paget's disease is that the
serum alkaline phosphatase level is increased to extreme
limits although serum calcium and phosphate levels are
normal.
• The disease often proceeds with exacerbations and
remissions.
• During remissions the value of alkaline phosphatase is usually
normal.

HISTOPATHOLOGY
• Varies remarkably, depending
upon the stage of the disease
encountered.
• Initial osteolytic phase-
disordered areas of resorption
by an increased no of large
osteoclasts.
• Osteoblastic phase- haphazard
laying of new bone matrix and
formation of woven bone
without regards to the pattern of
stress.

HISTOPATHOLOGY
• Repeated episodes of bone
removal and formation results in
the appearance of many small
irregularly shaped bone
fragments that appear to be
joined in a Jigsaw or mosaic
pattern, with deeply staining
hematoxyphilic reversal lines.
• Histologic hallmark of Pagets
disease.

• As the disease progresses, the osteoblastic phase
predominates and excessive abnormal bone formation
occurs.
• Pagetic bone is coarse and fibrous.
• Marrow spaces are filled with loose highly vascularized
connective tissue.
• Normal trabecular pattern is distorted with a mosaic pattern
of irregular cement lines joining areas of lamellar bone.
• No tendency to form Haversian systems and the bones are
very hard and dense.
• Eventually burned out phase predominates and new bone is
disordered, poorly mineralized and lacks structural integrity.
• Proliferation of bone and hypercementosis sometimes results
in obliteration of the periodontal ligament.

• On a radiograph, in the early stages, the density of bone is
decreased.
• As the disease progresses, osteoblastic activity is more than
osteoclastic activity; so that apposition exceeds resorption of
bone.
• The osteoblastic areas appear as patchy radiopacities and give
the characteristic "cotton-wool" appearance similar to that of
florid osseous dysplasia (chronic diffuse sclerosing
osteomyelitis).

• The lamina dura around the teeth in the involved regions may
be absent.
• The teeth may be hypercementosed only after the bony
changes in the jaw are manifested.
• The most serious complication of Paget's disease is osteogenic
sarcoma and occurs in 10% of the patients.
• On extraction of teeth in an affected part of bone, the wound
healing is disturbed and may result in suppurative
osteomyelitis.
• There is no specific treatment for Paget's disease.

CHERUBISM
• Also known as Hereditary fibrous dysplasia of the jaws,
Familial intraosseous swellings of the jaws, Familial
multilocular cystic disease of the jaws.
• Hereditary condition that produces firm, painless swellings
that occur bilaterally in the jaws, especially over the
mandibular angles.
• Autosomal dominant disease is usually detected between the
ages of 2 and 7 years.

• Mandible is more frequently
affected and produces full,
round lower face similar to
those of cherubs portrayed in
Renaissance religious
paintings.
• Often the eyes are upturned
to reveal the white sclera
beneath.
• Where the maxilla is involved,
the skin of the cheeks appears
to be stretched.
Photograph of a 7 year old boy with cherubism
showing bilateral swelling at the mandibular
angles.

• On a radiograph of the mandible, the expansion of the buccal
and lingual cortical plates is seen on occlusal and postero-
anterior views.
• The mandibular body and rami are frequently involved.
• Enlargement of the maxilla is at the expense of the maxillary
sinuses.
• The lesion consists of multiple cyst-like radiolucencies which
are located bilaterally in the jaws.

• These bilateral
multilocular
radiolucencies are a
characteristic feature
of cherubism.
• Teeth may be
unerupted and
displaced and some of
them appear to be
floating in the cyst-like
spaces. The lesions are typically multilocular giving a
characteristic ‘‘soap bubble’’ appearance, and
‘free floating teeth’.

HISTOPATHOLOGY
• The giant cells and areas of
haemorrhage are similar to
those seen in giant cell
granuloma.
• In cherubism the stroma tends
to be composed of fibrous
connective tissue with
fibroblasts arranged in sheets
with a slight storiform or
fascicular pattern.

• In some areas osteoclasts
are not conspicuous and
blood vessels are
prominent, and in some
cases may be surrounded by
a cuff of hyalinized collagen.

• This benign, self-limited disorder tends to regress after
puberty, thus eliminating the need for surgical intervention.
• Treatment, if necessary, consists of recontouring the bone for
cosmetic reasons after the lesions have stabilized in size.

FIBROUS DYSPLASIA
• A benign fibro-osseous lesion characterized by replacement
of bone with abnormal fibrous connective tissue interspersed
with varying amounts of calcification.
• The cause is unknown.
– One theory is it may be due to abnormal mesenchymal cell
function.
• Types of Fibrous Dysplasia
- Monostotic fibrous dysplasia
- Polyostotic fibrous dysplasia

Monostotic Fibrous Dysplasia
• Characterized by involvement of a single bone
– The maxilla is more frequently involved than the mandible.
– Most commonly diagnosed in children and young adults
with no sex predilection.
– Clinical examination reveals a painless swelling or bulging
of the buccal plate.

Polyostotic Fibrous Dysplasia
• Characterized by involvement of more than one bone.
– Typically occurs in children with a female predilection
– When long bones are involved, they may exhibit bowing
and an associated dull aching pain.
– Patients may have skin lesions appearing as light-brown
macules called café au lait spots.
– Association of fibrous dysplasia and intramuscular
myxoma is a rare disease known as Mazabrauds
syndrome. Association remains unclear but greater risk of
sarcomatous transformation in FD with Mazabrauds
syndrome has been reported.

Polyostotic Fibrous Dysplasia
• There are several types
– Craniofacial fibrous dysplasia
• Involves the maxilla with extension into the sinuses and
adjacent zygoma, sphenoid, and occipital bones.
– Jaffe type
• Involves multiple bones along with café au lait macules
on the skin
– Albright syndrome
• Characterized by endocrine abnormalities, precocious
puberty in females, stunting or deformity of skeletal
growth in both sexes as a result of premature closing of
the epiphyseal plates, café au lait spots.

Café au lait spots
• Pigmented macules or café-au-lait
spots are related to increased
amounts of melanin pigmentation
in the basal layers of the epidermis.
• Arranged in a linear or segmental
pattern near the midline of the
body.
• Usually over the lower lumbar
spine, sacrum, buttock, upper back,
neck and shoulders.
• May occur on the lips and oral
mucosa.
• May occur at birth, and occasionally
precede the development of
skeletal and endocrinal
abnormalities.

• Clinical and radiographic features
– A painless enlargement of affected bone or bones
– Typically, a painless, progressive, unilateral enlargement of
the mandible or maxilla.
– The classic radiographic appearance is a diffuse radiopacity
looking like “ground glass.”
– Radiographic changes blend into the surrounding normal
bone.

HISTOPATHOLOGY
• Classic appearance of dense
fibrous stroma of low to
moderate cellularity
surrounding irregularly shaped
bony trabeculae.
• This pattern has been
described as resembling
“Chinese characters.”
• No osteoblastic rimming of
trabeculae is seen.
Treatment: Surgical recontouring of bone for cosmetic reasons

CONCLUSIONS
• Multinucleated giant cells are commonly encountered in
various lesions of oral cavity.
• They may be characteristic for the lesion or exist just as a
reactive process, related to the elimination of microbes or
foreign materials.
• Nonetheless, they provide a vital clue to the diagnosis.
• Although, various theories have been put forward to explain
the genesis of the multinucleated giant cells, the exact
mechanism still remains enigmatic and interesting.
• So a definite criterion to identify individual giant cells in any
giant cell lesions however is required to assist the clinician
and researchers for proper diagnosis and management.

REFERENCES
• Shafer, Hine, Levy. Shafer’sTextbook of Oral pathology, 6th Edition; Elsevier:
2009.
• Regezzi JA, Sciubba JJ, Jordan RC. Oral Pathology Clinical Pathologic
correlations, 5th Edition; Saunders.
• Neville, Damm, Allen, Bouquot. Oral and Maxillofacial Pathology, 3rd
Edition; Saunders: 2009.
• Varghese I, Prakash A. Giant cell lesion of oral cavity. OMPJ 2011;2:976-
1225.
• Chattopadhyay A. Giant cells and giant cell lesions of the oral cavity.
Journal of Indian Dental Association. 1995;66 (11):326-327.
• J S Lee, M Tartaglia, B D Gelb, K Fridrich, S Sachs, C A Stratakis, M Muenke,
P G Robey,M T Collins, A Slavotinek Phenotypic and genotypic
characterisation of Noonan-like/multiple giant cell lesion syndrome. J Med
Genet 2005;42:e11

REFERENCES
• MK Gupta , SG Naidu, VJ Maheshwari Giant Cell Lesion of the Jaw: A Case
Report in a Child People’s Journal of Scientific Research Vol. 4(1), Jan.
2011, 63-67.
• Adrienne M. Flanagan, Paul M. Speight. Giant Cell Lesions of the
Craniofacial Bones. Head and Neck Pathol (2014) 8:445–453.
• William G. Brodbeck and James M. Anderson. GIANT CELL FORMATION
AND FUNCTION .Curr Opin Hematol. 2009 January ; 16(1): 53–57.
• Gabriela de Morais Gouvêa Lima, Janete Dias Almeida, Luiz Antonio
Guimarães Cabral. Cherubism: Clinicoradiographic Features and
Treatment.J Oral Maxillofac Res 2010 (Apr-Jun);1(2):e2
• D. P. Von Arx and A. Husain. Oral tuberculosis. BRITISH DENTAL JOURNAL
VOLUME 190 NO. 8 APRIL 28 2001 420-422.

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