Seminar on

GIANT CELL LESIONS OF ORAL CAVITY

Submitted by.
Lakshmi S Anand
MDS IIIrd year
INTRODUCTION
Giant cell : 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

TYPES OF GIANT CELLS

Physiologic Giant Cells

Physiological giant cells are the multinucleated giant cells that exist in normal
tissues.
eg. Osteoclast in bone, Trophoblast in placenta, Megakaryocytes in bone
marrow, skeletal muscle fibers

Pathologic Giant Cells

A. Giant Cell in Inflammation
(i) Foreign Body Giant Cells:
(ii)Langhan’s Giant Cell:
(iii)Touton Giant Cells:

Foreign Body Giant Cells

Inert foreign bodies initiate a tissue response in the form of foreign body
granuloma.
Foreign body giant cells are multinucleated giant cells associated with foreign
body reaction.
The nuclei are seen scattered throughout the cytoplasm. They are usually seen
when foreign material is too large for phagocytic removal by the macrophage
Langhan’s Giant Cell
Nuclei are arranged either around periphery in the form of horseshoe or ring or
cluster at the two poles of the giant cell.

Touton Giant Cells

• Multinucleated lipid laden cells.
• Nuclei are arranged in a circular pattern around a central eosinophilic
area. Vacuolated cytoplasm is seen between the nuclei and cell membrane
• Found in lesions containing cholesterol and lipid deposits
• Formed by the fusion of macrophages and are positive for histiocytic
markers like CD68, lysozyme, alpha-1 antitrypsin, and factor XIIIa
• Eg: xanthoma, xanthogranuloma, fibrous histiocytoma

Tumor giant Cells

• The large tumor cells with a single huge polymorphic nucleus or having
two or more nuclei.
• These nuclei are hyperchromatic and very large compared to the size of
the cell.
• The inflammatory giant cells like foreign body giant cells or Langhan’s
giant cell have normochromatic, small, normal looking nuclei which may
be numerous within one cell.
• Giant cell formation in tumors has been related to degree of anaplasia of
tumors

Reed Sternberg Cells

• Reed–Sternberg cells (also known as lacunar histiocytes for certain types)
are giant cells seen in Hodgkin's lymphoma (also known as Hodgkin's
disease; a type of lymphoma)
• Derived from B lymphocytes.
• Binucleated (‘owl eye nuclei’), although it may be multinucleated
("pennies on a plate"), with prominent nucleoli.
 • Immunophenotypically, Reed - Sternberg cells are positive for
CD15/CD30 and negative for CD45/CD20 both in nodal and extra nodal
disease.
Osteoclastic Giant Cells of Bone Tumors
• These tumors have uniform distribution of osteoclastic giant cells spread
in the stroma.

GIANT CELL FORMATION

The two theories:
i. Amitotic division of monocyte nuclei in the absence of cellular
division.
ii. Fusion of non replicating monocytes.
• Forkner at al (1930) observed two types of giant cells :
(based on experiments on the blood & tissues of rabbits )

• The first type contained a central rosette surrounded by nuclei in the

periphery - epitheloid or Langhans giant cell which was formed due to
nuclear division.
• Other group of cells with irregular arrangement of nuclei were considered
to be foreign body type giant cells and thought to arise due to fusion of
monocytes
• Auto-radiographic studies on the formation of giant cells revealed that
giant cells indeed form due to fusion which has been supported by other
authors.

MOLECULAR MECHANISM OF MACROPHAGE FUSION

 Induction of a fusion-competent status,
 Chemotaxis,
 Cell–cell attachment,
 Cytoskeletal rearrangements and
 Fusion
 CLASSIFICATION OF GIANT CELL LESIONS

1. Based on etiopathogenesis

CHATTOPADHYAY, 1995
A. Where giant cells are present in the concerned backgroundand 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
CHATTERJEE, ET AL. (2015)
• According to Paul Auclairet 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
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’slymphoma
• 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.
 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 cells
• 3. Melanocyte 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.

3. Based on origin and etiology (Chattopadhyay, 1995)

• 1. Damaged striated muscle fiber:
– a. Regenerating sarcolemmal 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 Hodgkins 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.

4. 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 (langhans giant
cell) and fungal infections
– c. Touton giant cells of xanthoma.

5. 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
• 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

6. Classification based on arrangement, composition of organelles and

function
I. Haythorn, et al., 1929
• (a) Langhans’ giant cells
• (b) FBGC
• (c) Osteoclasts
• (d) Megakaryocytes
• e) Muscle giant cells
• (f) Giant cells of nervous
II. Quinn MT and Schepetkin 2009
• (1) FBGCs
• (2) Langhans giant cells
• (3) Touton giant cells
• (4) Osteoclast-like cells
 • (5) Osteoclasts.

7. 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.
8. 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.
• 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
– • Aneurysmal bone cyst
– • Chondroblastoma
– • Chondromyxoid fibroma
– • Langerhans cell histiocytosis
– • Pigmented villonodular synovitis
• C. Malignant:
– • Osteosarcoma
– • Clear cell chondrosarcoma
– • Metastatic carcinoma
• 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
• Clinically, Chattopadhyay, et al. (1995) classification of giant cell lesion
according to origin is the most accepted and followed.
• Pathologically, Rosenberg, et al. (2001) is the most accepted and
followed classification.
CENTRAL GIANT CELL GRANULOMA
Non-neoplastic lesion formerly designated as "giant cell reparative
granuloma,“Lesions are designated as ‘giant cell granuloma’ or ‘giant cell
lesion’.
Age - 2 to 80 yrs, >60% cases occur before age 30
Female predilection
Approx. 70% cases arise in the mandible.
More common in the anterior portions of the jaws
Mandibular lesions frequently cross the midline.
Most are asymptomatic or painless expansion of the affected bone.
May be associated with pain, paresthesia, or perforation of the cortical bone
plate . Occasionally resulting in ulceration of the mucosal surface by the
underlying lesion
• Radiographically, they appear as radiolucent defects, which may be
unilocular or multilocular.Usually well delineated, but margins are non
corticated. Small unilocular lesions may be confused with periapical
granulomas or cysts. Multilocular giant cell lesion cannot be distinguished
radiographically - ameloblastoma or other multilocular lesions.
• Based on the clinical and radiographic features
1. Nonaggressive lesions make up most cases, exhibit few or no
symptom, demonstrate slow growth, and do no show cortical perforation or
root resorption of teeth
2. Aggressive lesions are characterized by pain, rapid growth, cortical
perforation and root resorption. They show a marked tendency to recur after
treatment compared with the nonaggressive type.
Few to many multinucleated giant cells in a background of ovoid to spindle-
shaped mesenchymal cells.
Giant cells may represent osleoclasts or macrophages
The giant cells may be aggregated focally in the lesional tissue or may be
present diffusely throughout the lesion.
Giant cells vary considerably in size and shape from case to case, some are
small and irregular in shape and contain only a few nuclei.
In other cases, the giant cells are large and round and contain 20 or more
nuclei.The stroma may be loosely arranged and edematous or it may be
quite cellular. Areas of erythrocyte extravasation and hemosiderin deposition
often are prominent. Older lesions may show considerable fibrosis of the
stroma. Foci of osteoid and newly formed bone are occasionally present
within the lesion.
Lesions showing large, uniformly distributed giant cells and a predominantly
cellular stroma appear more likely to be clinically aggressive with a greater
tendency to recur after surgical treatment.
Because giant cell granulomas are histopathologically identical to brown
tumor hyperparathyroidism should be ruled out in all instances.
Multifocal involvement in childhood suggests cherubism and warrants
further investigations.
 They are usually treated by curettage.
 Recurrence rate range from 11 to 50%.
 Some aggressive lesions require radical cure.
 Long term prognosis of giant cell granuloma is good and metastases do
not develop.

PERIPHERAL GIANT CELL GRANULOMA

Also called giant as cell epulis
Relatively common tumor like growth
Not a true neoplasm ,rather is a reactive lesion caused by trauma or local
irritation.
Close microscopic resemblance to central giant cell granuloma
Believed to be a soft tissue counter part of this central bony lesion.
Peak incidence - fifth and sixth decades of life
Approximately 60% occur in females.
It may develop in either the anterior or posterior region of the gingiva or
alveolar mucosa
Mandible is affected slightly more often than the maxilla.
Red or reddish-blue nodular mass
Sessile or pedunculated mass,may or may not be ulcerated.
Most lesions are smaller than 2cm in diameter
The clinical appearance is similar to the more common pyogenic granuloma
of the gingiva.
‘Cupping’ resorption of the underlying alveolar bone sometimes is seen.
On occassion it may be difficult to determine whether the mass arose as a
peripheral lesion or as a central giant cell granuloma that eroded through the
cortical plate into the gingival soft tissues.
Proliferation of multinucleated giant cells within a background of plump
ovoid and spindle-shaped mesenchymal cells. The giant cells may contain
only a few nuclei or several dozen. Some of these cells may have large,
vesicular nuclei; others demonstrate small, pyknotic nuclei. Mitotic figures
are fairly common in the background mesenchymal cells. Abundant
hemorrhage - hemosiderin pigment, especially at the periphery of the
lesion.The overlying mucosal surface is ulcerated in about 50% of cases. A
zone of dense fibrous connective tissue usually separates the giant cell
proliferation from the mucosal surface. Acute and chronic inflammatory
cells are frequently present. Areas of reactive bone formation and dystrophic
calcification are not unusual.
 Local surgical excision down to the underlying bone.
 Adjacent teeth should be carefully scaled
 Apptoximately 10% of lesions are reported to recur, and reexcision must
be performed.

GIANT CELL FIBROMA

It is a fibrous tumour with distinctive clinicopathologic features.
It represent 2 to 5% of all oral fibrous proliferations.
It doesn’t appear to be associated with chronic irritation.
 Asymptomatic sessile or pedunculated nodule
Usually less than 1 cm in size.Surface often appears papillary – papilloma
Lesion usually occurs at a younger age. In about 60% of cases, the lesion is
diagnosed during the first 3 decades of life.Slight female predilection
Approx 50% of all cases occur on the gingiva
The mandibular gingiva is affected twice as often as the maxillary gingiva.
The tongue and palate also are common sites.
It reveals a mass of loosely arranged vascular fibrous connective tissue
Numerous large, stellate fibroblasts within the superficial connective tissue
which may contain several nuclei.
The covering epithelium is thin and atrophic, although reteridges may appear
narrow and elongated.

TUBERCULOSIS
It is a chronic, infectious, granulomatous disease
Caused by Mycobacterium tuberculosis, M.bovis and other species – acid
fast bacteria
Direct person-person spread through air borne droplets from a patient with
active disease
Primary tuberculosis –
Previously unexposed people
Mostly involve lungs
Results only in a localized, fibrocalcified nodule at initial site of involvement
In 95% cases development of cell mediated immunity controls infection.
Organisms may remain dormant in nodules for years
Progressive primary tuberculosis.
Usually asymptomatic. Occasionally, fever and pleural effusion may occur.
Secondary Tuberculosis:
Pattern of disease that arises in a previously sensitized hosts
Reactivation of dormant primary lesion
Weakened host resistance
Lesions classically localized to apex of lung
Spread to different sites by expectorated infected material or through
lymphatic or vascular channel – miliary tuberculosis
Low grade fever, malaise , anorexia weight loss and night sweats
Productive cough, haemoptysis or chest pain
Extrapulmonary tuberculosis:
Any organ can be involved
Lymphatic system, skin, skeletal system, CNS, kidney and gastrointestinal
system
Lupus vulgaris – primary involvement of skin, papular nodules frequently
ulcerates & commonly seen on face
In H&N – most common cervical lymph node, larynx, middle ear
Oral lesions:
Uncommon
Usually secondary& seldom primary
Tongue is most common site
Followed by the palate, lips, buccal mucosa, gingiva and frenula
Irregular, superficial or deep, painful ulcer which tends to increase slowly in
size
Gingival lesion appears as a diffuse, hyperemic, nodular or papillary
proliferation
Scrofula :
Exhibit enlargement of oropharyngeal and cervical lymph node
Develop significant amount of caseation
Form numerous fistulas through overlying skin
Calcification of nodes – radiographically seen
Histopathology
Granulomas (tubercle) – circumscribed collections of epitheloid histiocytes,
lymphocytes and multinucleated giant cells
Central caseous necrosis
Diagnosis
Tuberculin test (Mantoux or PPD)
Special mycobacterial stains
Culture of infected sputum or tissue

LEPROSY
Chronic granulomatous infection
Caused by acid fast bacillus, Mycobacterium leprae.
Bacillus is highly temperature dependent
Lesions seen in cooler parts of body like skin, nasal cavity and palate.
Ridley and Jopling’s classification
Tuberculoid leprosy(TT) and
Lepromatous leprosy (LL)
Intermediate Groups:
Borderline tuberculoid (BT),
Borderline leprosy (BB), and
Borderline lepromatous (BL)
Tuberculoid leprosy: (paucibacillary)
Single or multiple macular, erythematous eruptions
Dermal nerve and peripheral nerve trunk involvement - loss sensation, loss
of sweating
Oral lesions are rare
Lepromatous leprosy (multibacillary):
Ill defined erythematous macules or papules that subsequently lead to
thickening of skin
Face is common site
Thickening of skin leads to distorted face (leonine facies)
Hairs, eyebrows and lashes are lost
Nasal involvement – nosebleeds, stuffiness
Collapse of bridge of nose considered pathognomonic
Oral manifestations:
Not rare in multibacillary leprosy
Hard palate- soft palate- lips- buccal maxillary –gingival -labial mandibular
gingiva and buccal mucosa.
Yellowish to red, sessile, firm, enlarging papule and small tumour-like
masses called lepromas, which show a tendancy to break down and ulcerate.
Gingival hyperplasia with loosening of the teeth has also been described.
Facies leprosa involve
Atrophy of anterior nasal spine,
Atrophy of ant. maxillary alveolar ridge and
Endonasal inflammatory changes.
Maxillary involvement in children - enamel hypoplasia and short tapering
roots.
Dental pulp infection - internal resorption or pulpal necrosis - obvious red
discoloration of crown.
Facial paralysis unilateral or bilateral
Maxillary nerve involvement – sensory defect
Histopathology
Tuberculoid leprosy
Typical granulomatous nodule showing collections of epitheloid cells and
lymphocytes in a fibrous stroma.
Langhans-type giant cells are variably present.
Bacilli - +
Lepromatous leprosy:
No well formed granulomas
Typical finding is sheets of lymphocytes intermixed with vacuolated
macrophages called lepra cells
Bacilli - ++++
Definitive diagnosis –
Clinical presentation and demonstration of organism on smear or tissue
Treatment -
Paucibacillary – 6 month regimen
Rifampicin & Dapsone
Multibacillary – 24 month regimen
Rifampicin, Dapsone & Clofazimine

ACTINOMYCOSIS
Chronic granulomatous suppurative and fibrosing disease
Actinomyces - anaerobic or microaerophilic gram-positive nonacid fast,
branched filamentous bacteria
Normal saprophytic component of oral flora, colon, and vagina and none are
known to be recoverable from the environment.
A. israelii, A. viscosus, A. odontolyticus, A.naeslundii or A. meyeri.
Seen in dental plaque, dental calculus, necrotic pulp, and tonsils

Pathogenesis
Not entirely known.
Appears to be an endogenous infection and not communicable.
Does not appear to be an opportunistic infection in a situation of depressed
cell-mediated immunity.
Trauma seems to play a role in some cases by initiating a portal of entry for
the organisms, since they are not highly invasive. Thus the extracted socket,
periodontal pocket, nonvital tooth, or mucosal abrasion may act as the portal
of entry for the infection.
The disruption of the mucosal barrier is the main step in the invasion of
bacteria.
Initial acute inflammation is followed by a chronic indolent phase.
Lesions usually appear as single or multiple indurations.
Central fluctuance with pus containing neutrophils and sulphur granules is
diagnostic of the disease.
The fibrous walls are typically described as woody.
It occurs in association with HIV infection, transplantation, chemotherapy,
herpes, and cytomegaloviral ulcerative mucosal lesions. It is also reported in
osteoradionecrosis and in patients with systemic illness.
Clinical Features
Cervicofacial actinomycosis
Most common
The organisms may enter the tissues through the oral mucous membranes
and may either remain localized in the subjacent soft tissues or spread to
involve the salivary glands, tongue, very rarely gingiva, bone or even the
skin of the face and neck, producing swelling and induration of the tissue.
These soft tissue swellings eventually develop into one or more abscesses,
which tend to discharge upon a skin surface, rarely a mucosal surface,
liberating pus containing the typical ‘sulfur granules’.
The skin overlying the abscess is purplish red, indurated and has the feel of
wood or often fluctuant.
It is common for the sinus through which the abscess has drained to heal, but
because of the chronicity of the disease, new abscess develop and perforate
the skin surface. Thus the patient, over a period of time, may show a great
deal of scarring and disfigurement of the skin.
The infection of the soft tissues may extend to involve the mandible, or less
commonly, the maxilla which results in actinomycotic osteomyelitis. If the
bone of the maxilla is invaded, the ensuing specific osteomyelitis may
eventually involve the cranium, meninges, or the brain itself. Once the
infection reaches the bone, the destruction of the tissue may be extensive.
Such destructive lesions within the bone may occur or localize at the apex of
one or more teeth and simulate a pulp-related infection such as a periapical
granuloma or cyst.
Abdominal actinomycosis
extremely serious form of the disease
high mortality rate.
In addition to generalized signs and symptoms of fever, chills, nausea and
vomiting, intestinal manifestations develop, followed by symptoms of the
involvement of other organs such as the liver and spleen.
Pulmonary actinomycosis
similar findings of fever and chills accompanied by a productive cough and
pleural pain. The organisms may spread beyond the lungs to involve adjacent
structures.
Histologic features
Granulomatous lesion showing central abscess formation within which may
be seen the characteristic colonies of microorganisms.
These colonies appear to be floating in a sea of polymorphonuclear
leukocytes, often associated with multinucleated giant cells and
macrophages particularly around the periphery of the lesion.
The individual colony, which may appear round or lobulated, is made up of a
meshwork of filaments that stains with hematoxylin, but shows eosinophilia
of the peripheral club shaped ends of the filaments.
This peculiar appearance of the colonies, with the peripheral radiating
filaments, is the basis for the often-used term ‘ray fungus.’
The tissue surrounding the lesion exhibits fibrosis.
Methenamine silver stain can demonstrate the organisms better.
 Diagnosis
The diagnosis of actionomycosis depends not only upon clinical findings in
the patient and the demonstration of the organisms in the tissue section or
smear, but also upon their culture.
Treatment and prognosis
The treatment of this disease is difficult and has not been uniformly
successful.
Long standing fibrosis cases are treated by draining the abscess, excising the
sinus tract with high doses of antibiotics.
Long term high dose penicillin, tetracycline and erythromycin have been
used most frequently, but the course of the disease is still often prolonged, In
addition to this surgical drainage of the abscesses and excision of sinus tract
is necessary to accelerate healing.

SARCOIDOSIS
Multisystem granulomatous disease
Unknown aetiology
Most commonly affecting young individuals
Presented mostly as hilar lymphadenopathy ,pulmonaryinfiltration, skin and
eye lesions.
Disease is characterized by a depression of delayed-type hypersensitivity
suggesting an impaired cell mediated immunity, and raised or abnormal
serum immunoglobulins suggesting lymphoproliferation.
Prolonged antigenemia, circulating immune complexes and serum inhibitors
all contribute to the disorder - James et al
Most common in the lungs, skin, lymphnodes, salivary glands, spleen and
bones,
Practically may involve any site, including the mouth.
Clinical signs and symptoms are frequently less severe enough to cause
alarm.
Mild malaise and cough with involvement of specific organs may occur.
Cutaneous lesions - raised red patches that occur in groups, grow slowly and
do not ulcerate or crust.
Scattered, non specific, tender erythematous nodules - Erythema nodosum
occur in about 15% of cases.
Involvement of lymphnodes and salivary glands is manifested by nodular
enlargement.

Lofgren’s syndrome – acute form of sarcoidosis

Erythema nodosum
Bilateral hilar lymphadenopathy
Arthralgia

Heerfordt’s syndrome (uveoparotid fever) – rare presentation of

sarcoidosis
1. Parotid enlargement
2. Ant. Uveitis of the eye
3. Facial paralysis
4. fever

Oral manifestations
• Lips - small, papular nodules or plaques, or resemble herpetic lesions or
"fever blisters".
• Palate and buccal mucosa – bleblike lesion containing a clear yellowish
fluid, or as solid nodules.
• Sarcoid may produce diffuse destruction of the bone. (Hillcrup and Vein
Vlaarsscveen and colleagues).
• Sarcoid lesions closely resemble proliferating noncaseating nodules of
tuberculosis
• Absence of acid-fast organisms can be demonstrated in tissue sections of
sarcoidosis.
 • Nest of epithelioid cells,withlanghan’s or foreign body type giant cell are
one of the chief microscopic features of the fibrous granulomatous nodules.
• These granulomas also contain T and B cell as well as various
immunoglobulins that can be identified by appropriate immunofluorescence.
• Caseation and necrosis do not occur, although the granuloma transforms
into a solid amorphous, eosinophlic, hyaline mass as it ages.
• Schaumann bodies – laminated basophilic calcifications
• Asteroid bodies – inclusion bodies
• Diagnosis is established by the clinical presentation, histopathologic
appearance and the presence of negative findings with both special stains
and cultures for organism.
• An intracutaneous test for the diagnosis of sarcoidosis, the Kveim-
Siltzbach test, has been devised.
• In approximately 60% of patients, symptoms resolve within 2 years
without treatment.
• Of those affected 20% can be treated successfully by corticosteroids.
• Significant involvement- methotrexate, azathioprine, chlorambucil and
cyclophosphamide
• 2-4% die due to CNS complications.

HYPERPARATHYROIDISM
Excess production of parathyroid hormone (PTH) results in the condition
known as hyperparathyroidism.
PTH normally is produced by the parathyroid glands in response to a
decrease in serum calcium levels.
Primary hyperparathyroidism is the uncontrolled production of PTH, usually
as a result of a parathyroid adenoma or hyperplasia, rarely a parathyroid
carcinoma.
Secondary hyperparathyroidism develops when PTH is continuously
produced in response to chronic low level of serum calcium, a situation
usually associated with chronic renal disease.
Primary hyperparathyroidism - older than 60 yrs
Female predilection
Classic triad of signs and symptoms of hyperparathyroidism are described as
having "stones, bones and abdominal groans".
Marked tendency to develop renal calculi (kidney stones, nephrolithiasis)
Metastatic calcifications
Frequently involving other soft tissues, such as blood vessel walls,
subcutaneous soft tissues, the sclera, the dura, and the regions around the
joints
The osseous changes in conjunction with primary hyperparathyroidism
One of the first clinical signs of this disease is seen radiographically as
subperiosteal resorption of the phalanges of the index and middle fingers
Generalized loss of the lamina dura surrounding the roots of the teeth is also
seen as an early manifestation of the condition.
Alterations in trabecular pattern characteristically develop in next phase
A decrease in trabecular density and blurring of the normal trabecular pattern
occur often as ‘ground glass appearance’
These lesions appear radiographically as well demarcated unilocular or
multilocular radiolucencies.
Commonly affect the mandible, clavicle, ribs and the pelvis
• May be solitary but are often multiple, and longstanding lesions may
produce significant cortical expansion
Most severe skeletal malformation is osteitis fibrosa cystica, a condition that
develops from the central degeneration and fibrosis of longstanding brown
tumours
In secondary hyperparathyroidism, enlargement of jaws produce a ground-
glass radiographic pattern.
Abdominal groans refer to the tendency for the development of duodenal
ulcers.
In addition, changes in mental status are often seen, ranging from lethargy
and weakness to confusion and dementia.
Called brown tumor of hyperparathyroidism
Histopathologic features
Identical to the central giant cell granuloma of the jaws
Characterized by a proliferation of exceedingly vascular granulation tissue,
which serves as a background for numerous multinucleated osteoclast-
type giant cells.
Some lesions may also show a proliferative response characterized by a
parallel arrangement of spicules of woven bone set in a cellular fibroblastic
background with variable numbers of multinucleated giant cells.
This pattern is often associated with secondary hyperparathyroidism related
to chronic renal disease (renal osteodystrophy).
Treatment and Prognosis
In primary hyperparathyroidism, the hyperplastic parathyroid tissue or the
functional tumor must be removed surgically to reduce PTH levels to normal
Secondary hyperparathyroidism –
Restriction of dietary phosphate, use of phosphate-binding agents
Pharmacologic treatment with an active vitamin D metabolite (eg:calcitriol)
Exposure to aluminium salts is eliminated
Parathyroidectomy
Renal transplantation

ANEURYSMAL BONE CYST

Aneurysmal bone cyst is an intraosseous accumulation of variable-sized,
blood-filled spaces surrounded by cellular fibrous connective tissue
Often admixed with trabaculae of reactive woven bone.
The cause and pathogenesis is poorly understood.
It may arise from a traumatic event
Vascular malformation or neoplasm that disrupts the normal osseous
hemodynamics and lead to an enlarging hemorrhagic extravasation.
Aneurysmal bone cyst may occur either as a primary lesion or as a result of
disrupted vascular dynamics in a preexistingintrabony lesion.
 Most frequent site - the shaft of a long bone
Gnathic aneurysmal bone cysts are uncommon, with approximately 2%
reported from the jaws
Children and young adults
No significant sex predilection
Majority cases - posterior segment of mandible.
Swelling usually develops rapidly.
Pain is reported
paresthesia, compressibility, and crepitus are rarely seen
On occasion, malocclusion, mobility, migration, or resorption of involved
teeth may be present
Maxillary lesions often bulge into the adjacent sinus
Nasal obstruction, nasal bleeding, proptosis, and diplopia are noted
uncommonly
Unilocular or multilocular radiolucent lesion
Marked cortical expansion and thinning
The radiographic borders are variable and may be well defined or diffuse
A ballooning or "blow-out" distension of the contour of the affected bone is
described
Uncommonly, small radioopaque foci - small trabeculae of reactive bone, are
noted within the radiolucency.
At the time of surgery, intact periosteum and a thin shell of bone are
typically found covering the lesion
Cortical perforation may occur, but spread into the adjacent soft tissue not
seen
When the periosteum and bony shell are removed, dark venous blood
frequently wells up and venous like bleeding may be encountered
The appearance at surgery has been likened to that of a "blood-soaked
sponge."
Spaces of varying size, filled with unclotted blood
Surrounded by cellular fibroblastic tissue containing multinucleated giant
cells and trabaculae of osteoid and woven bone
On occasion, the wall contains an unusual lacelike pattern of calcification
that is uncommon in other lesions
The blood-filled spaces are not lined by endothelium.
 Curettage or enucleation, supplemented with cryosurgery.
 Recurrence rates are variable,8% - 60%
 Recurrence due to inadequate or subtotal removal upon initial therapy.
 Overall, in spite of recurrences, the long-term prognosis appears
favorable.

CHERUBISM
Rare developmental jaw condition that is generally inherited as an autosomal
dominant trait with high penetrance but variable expressivity
Facial appearance is similar to that of the plump-cheeked little angels
(cherubs)
Also known as Familial fibrous dysplasia
Usually occurs between the ages of 2 and 5 years
Clinical alterations typically progress until puberty, then stabilize and slowly
regress.
Cherublike facies - bilateral involvement of the posterior mandible that
produces angelic chubby cheeks
“Eyes upturned heaven" appearance
On occasion, affected patients also reveal marked cervical lymphadenopathy.
The mandibular lesions - appear as a painless, bilateral expansion of the
posterior mandible that tends to involve the angles and ascending rami
Bony expansion is usually bilaterally symmetrical
Severe cases, most of the mandible is involved
Milder maxillary involvement occurs in the tuberosity areas, in severe cases
the entire maxilla can be affected.
 Extensive bone involvement causes a marked widening and distortion of the
alveolar ridges
Aesthetic and psychologic impact
Enlargements cause tooth displacement or failure of eruption, impair
mastication, create speech difficulties
Multilocular expansile radiolucency
Histopathologic Features
Similar to those of isolated giant cell granulomas and they seldom permit a
specific diagnosis of cherubism in the absence of clinical and radiologic
information
Lesional tissue consist of vascular fibrous tissue containing variable numbers
of multinucleated giant cells
Giant cells tend to be small and usually aggregated focally
Foci of extravasated blood are commonly seen.
Stroma is loosely arranged than that seen in giant cell granuloma
Eosinophilic, cufflike deposits surrounding small blood vessels throughout
the lesion - specific for cherubism
In older, resolving lesions of cherubism, the tissue becomes more fibrous,
the number of giant cells decreases, and new bone formation is seen.
 The lesion tend to show varying degrees of remission and involution after
puberty
 By the fourth decade the facial features of most patients approach
normalcy
 In occasional patients, the deformity can persist.
 Early surgical intervention with curettage of the lesion
SOLITARY BONE CYST
The simple bone cyst is a benign, empty, or fluidcontaining cavity within bone
that is devoid of an epithelial lining. The lesion is undoubtedly more common in
the jaws than the literature would indicate. The causeand pathogenesis are
uncertain and controversial. Several theories have been proposed , but none of
them explains all of the clinical and pathologic features of this disease.
The trauma-hemorrhage theory has has been proposed .
This theory suggests that trauma to the bone that is insufficient to cause a
fracture results in an intraosseous hematoma. If the hematoma does not
undergo organization and repair, it may liquefy, resulting in a cystic defect.
Other etiologic theories include inability of interstitial fluid to exit the bone
because of inadequate venous drainage, local disturbance in bone growth,
ischemic marrow necrosis, and localized alteration in bone metabolism resulting
in osteolysis.
Clinical and Radiographic Features
Simp le bone cysts have been repo rted in almost every bone of the body, but
the vast majority involves the long bones. Simple bone cysts with in the jaws
are common and most frequently encountered in patients between10 and 20
years of age. The lesion is rare in children under age five and is seldom seen in
patients over age 35.
Simple bone cysts of the jaws are essentially restricted to the mandible.
although there have been reports of the lesion in the maxilla. Bilateral simple
bone cysts of the mandible arc occasionally encountered. About 60% of
cases occur in males.
The simple bone cyst usually produces no symptoms and is discovered only
when radiographs are taken for some other reason. About 20% of patients,
however, have a pain less swelling of the affected area. Pain and paresthesia
may be noted in a few cases. Although any area of the mandible may be
involved, simple bone cysts are more common in the premolar and molar areas.
Radiographically, the lesion most frequently appears as a well -delineated
radiolucent defect. In some areas. the margins of the defect are sharply defined;
in other areas, the margins are ill defined. The defect may range from I to 10 cm
in diameter. When several teeth are involved in the lesion , the radiolucent
defect often shows domelike projections that scallop upward between the
roots. This feature is highly suggestive but not diagnostic of a simple bone cyst.
Teeth that appear to be involved in the lesion are generally vital and do not
show root resorption. Although not characteristic, a simple bone cyst may
rarely appear as a multilocular radiolucency associated with cortical expansion
and slow enlargement. When expansion is present , an occlusal radiography
demonstrates a thin shell of cortical bone that exhibits no further reactive
changes. Extensive lesions involving a substantial portion of the body and
ascending ramus are occasionally encountered.
Similar simple cysts may be associated with lesions of cemento-osseous
dysplasia and other fibre –osseous proliferations. These typically occur in older
patients .
CONCLUSION
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. It is
necessary to correlate clinical, radiographic, histologic & sometimes laboratory
findings to arrive at a diagnosis.
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
i. Textbook of Oral Pathology – Shafer 8th edition
ii. Oral & Maxillofacial Pathology – Neville, 2nd edition
iii. Robbins Basic Pathology -7th edition
iv. Giant Cells in Health and Disease-A Review - Sonal Gupta, Harshminder
Kaur, ParvindGumber, Nida Fahmi, Kanchan Sharma4 Arvind Gumber :
International Journal of Community Health and Medical Research Vol.2
Issue2 2016
v. Classifying Giant Cell Lesions: A Review - Vikash Ranjan, Sambuddha
Chakrabarty, Pallak Arora, Trisha Rastogi : 2018 Journal of Indian
Academy of Oral Medicine & Radiology Published by Wolters Kluwer -
Medknow
vi. Giant Cell Lesions Of Oral Cavity - Ipe Varghese, Ashwin Prakash : Oral
& Maxillofacial Pathology Journal [ OMPJ ] Vol 2 No 1 Jan- Jun 2011
ISSN 0976-1225
vii. Nagar SR, Joy T, Ahire MS, Sinha A, D'souza ZI, Pakhmode V. Giant
Cells: An Overview!!!.
viii. Shrestha A, Marla V, Shrestha S, Neupane M. Giant cells and giant cell
lesions of oral cavity-a review. Cumhuriyet Dental Journal. 2014
Jan;17(2):192-204.