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Review Article

Giant cell lesions of the oral cavity

Sreeja Chellaswamy, Pavithra Manohar, Beeula Rajakumari, Sathish Muthukumar Ramalingam,
Vijayashree Ragavan1, Nachiammai Nachiappan
Departments of Oral and Maxillofacial Pathology, Chettinad Dental College and Research Institute, 1Department of General Pathology,
Chettinad Hospital and Research Institute, Kelambakkam, Chennai, Tamil Nadu, India

ABSTRACT
Giant cells are formed by the union of several monocytes or macrophages which undergo
a defined set of intercellular interactions that ultimately results in a multinucleated cell
with a single cytoplasmic compartment. Giant cells are not only pathologic, there are
even physiologic giant cells such as osteoclast, megakaryocytes, and trophoblast that
helps in maintaining normal repair and remodeling process in the body. There are various
classifications and theories for the formation of giant cells. Some of these giant cells act
as a characteristic histopathologic feature in oral lesions and aid in diagnosis. In the field
of challenging diagnosis, these characteristic features can provide a clue for diagnosing
some oral lesions. On this background, the article was attempted to review various types
of giant cells, their formation, and giant cell lesions of the oral cavity with basic information
about their clinical, radiologic, histopathological features, and treatment planning.

Key words: Giant cell lesions of the oral cavity, macrophages, multinucleated giant cells

INTRODUCTION classifications, formation of giant cells, and various giant cell

Giant cell lesions are a group of heterogeneous clinical
entities that affect the jaws. These lesions typically display
multinucleate giant cells as one of the characteristic
histopathological features which are significant and aids in
diagnosis. Giant cells are large, multinucleated, modified
macrophages recognized easily in light microscopy. They
are formed by coalescing or the fusion of mononuclear cells
or nuclear division of monocytes.[1] It was first described by
Virchow and it is also known as polykaryocytes or syncytium.
There are several traditional literature speaking about
Address for correspondence:
Dr. Sreeja Chellaswamy,
Department of Oral and Maxillofacial Pathology, Chettinad Dental
College and Research Institute, Kelambakkam, Chennai ‑ 603 103,
Tamil Nadu, India.
E‑mail: sreejagobu@gmail.com
lesions separately. In this article, we are attempting to collate
all the aspects of giant cells starting from their formation,
various types of giant cells and clinical, radiological,
histopathological features, histochemical markers, and
treatment planning of various giant cell lesions which would
be a greater help for the pathologists.
CLASSIFICATION
Giant cells can be classified based on etiopathogenesis, origin,
types, arrangement, and function. Although there is typically
a focus on the pathological aspects of multinucleated giant
cells, they also play an important physiological role in body
repair and remodeling mechanism.[2]
Giant cells are classified based on their functional characteristics
[Table 1], [2] based on etiopathogenesis [Table 2], [3,4]

Received: 11‑10‑2020, Revised: 23-12-2020, This is an open access journal, and articles are distributed under the
Accepted: 13‑01‑2021, Published: 30‑03‑2021 terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike
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DOI: How to cite this article: Chellaswamy S, Manohar P, Rajakumari B,

10.4103/srmjrds.srmjrds_106_20 Ramalingam SM, Ragavan V, Nachiappan N. Giant cell lesions of the
oral cavity. SRM J Res Dent Sci 2021;12:27-36.

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Sreeja, et al.: A review on giant cell lesions of the oral cavity

based on pathognomonic and nonpathognomonic The fusion of the macrophages was described by different
association [Table 3], and[4,5] based on origin in the form of authors and various theories were put forth. There are a few
flowchart [Figure 1].[6] proposed mechanism by Singer and Nicolson, 1872 – the
lipid bilayer present in the cell wall is responsible for the
FORMATION OF GIANT CELL attachment between two cells and Heine and Schnaitman,
1971 – direct interaction between the viral envelop and
Monocytes or macrophages are leukocytes which cell surface in which antigens from the viral envelop gets
functions as a phagocytic cell and aids in the removal of incorporated into the polykaryon membrane, which forms
the pathogenic antigens and foreign materials from the the bridge between two cells resulting in fusion.[8]
body. They are large mononucleated cells that play an
important role in innate as well as acquired immunity. The two theories of giant cell formation are;
They are involved commonly in the chronic inflammation 1. Nuclear division of monocytes with the absence of
and sometimes in the later stage of acute inflammation. cytoplasmic division
The important function of these cells is to remove the 2. Fusion between monocytes.
pathogenic antigens or foreign material from the body,
when the individual macrophages are unable to remove These theories were explained by experiments conducted
the foreign particles they join or fuse together to form by Forkner in 1930 – two giant cells were formed in which
large multinucleated giant cells.[7] There are a series of one showed a rosette pattern of nuclear arrangement at the
steps involved in the giant cell formation, which include periphery (Langhans type) and other showed an irregular
recognition, adhesion, fusion, and activation. arrangement of nuclei (foreign body type), from this he
stated that peripheral arrangement of nuclei can be due to
Table 1: Classification of giant cells based on their nuclear division of monocytes and the irregular pattern can
functional characteristics be due to fusion of monocytes [Figure 2].[3]
Physiological giant cells
Osteoclast Concepts on the fusion of giant cells;
Megakaryocytes
Trophoblast in placenta
1. Immune‑mediated concept – lymphokines and cell
Pathological giant cells surface changes facilitate fusion of macrophages
Langhans type - tuberculosis 2. Young and old macrophage concept – recognition of old
Foreign body - actinomycosis macrophages, which shows chromosomal abnormality
Touton giant cell - xanthoma
and altered cell surface which stimulates the fusion
Warthin-Finkeldey giant cell - measles
Aschoff giant cell - fibrinoid necrosis, rheumatoid heart disease process between old and young macrophages
3. Endocytic activity concept – two or more macrophages try to
Reed-Sternberg giant cell - Hodgkin’s lymphoma
ingest or engulf the same antigen the resulting phagocytosis
causes fusion of endosome margins between two cells.[1]
Table 2: Classification of giant cell lesions based on
etiopathogenesis
Inflammatory TYPES OF GIANT CELLS
Chronic osteomyelitis, orofacial granulomatosis, sarcoidosis,
periapical cyst Physiological giant cells
Infectious
Bacterial Megakaryocytes
Tuberculosis • Structure: They are large polypoidal cells present in the
Leprosy
Syphilis
bone marrow. It has a multinucleated or multilobed
Actinomycosis nucleus with the presence of prominent cytoplasm and
Cat scratch disease azurophilic granules [Figure 3]
Viral • Formation: Megakaryocytes are physiological giant cells
Herpes
arising from hematopoietic stem cells. They undergo
Measles
Fungal multiple endocytosis leading to the formation of
Histoplasmosis multinucleate giant cell. These are platelet precursors
Blastomycosis involved in platelet formation.[9]
Cryptococcosis
Paracoccidioidomycosis
Idiopathic‑ external root resorption Osteoclasts
Reactionary‑ peripheral giant cell granuloma
Destructive‑ central giant cell granuloma, giant cell fibroma
• Structure: They morphologically resemble foreign body
Metabolic‑ hyperparathyroidism giant cells but have less number of nuclei, usually each
Developmental‑ fibrous dysplasia cell has 10–20 nuclei present on the endosteal surfaces
Vascular‑ aneurysmal bone cyst within the Haversian system of bone [Figure 4]
Bone disease‑ Paget’s disease • Formation: they are terminally differentiated
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Sreeja, et al.: A review on giant cell lesions of the oral cavity

Figure 1: Flowchart depicting types of giant cells based on origin

Table 3: Classification of giant cell lesions based

on the etiopathogenesis, with pathognomonic and
nonpathognomonic association
Lesion where giant cells are pathognomonic
Giant cell fibroma
Peripheral giant cell granuloma
Giant cell tumor
Hodgkin disease
Lesion where GC is characteristic but not pathognomonic
Tuberculosis
HSV infection
Measles
Cherubism
Xanthoma
Lesions associated with the presence of giant cells
Figure 2: Formation of giant cells Orofacial granulomatosis
Fungal infection foreign body reactions
Neoplasms
Syphilis
Leprosy
Fibrous dysplasia
Paget’s disease of the bone
Aneurysmal bone cyst
Ossifying fibroma
Wegener’s granulomatosis
Actinomycosis
Chronic diffuse sclerosing osteomyelitis
Odontogenic giant cell fibromatosis
Heerfordt’s syndrome
GC: Giant cell, HSV: Herpes simplex virus 1

multinucleated cells which originate from the

mononuclear cells of the hematopoietic stem cell lineage.
Two cytokines are involved in the formation of osteoclasts,
Figure 3: Megakaryocytes namely Receptor Activator of Nuclear Factor Kappa

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Sreeja, et al.: A review on giant cell lesions of the oral cavity

β Ligand and macrophage colony‑stimulating factor.

In addition to these cytokines, several other systemic
hormones and growth factors influence the formation
and function of these cells. They play an important role
in bone remodeling and calcium homeostasis.[1]

Trophoblasts
• Structure: They have an outer layer of cytotrophoblast,
inner layer of syncytiotrophoblast, and an intermediate
layer
• Formation: Trophoblasts are the cells formed in the first
stage of pregnancy and are the first cells to differentiate from
the fertilized egg. From the blastomere, trophoectoderm
develops that gives extraembryonic ectoderm. This
gives rise to chorion and ectoplacental cone leading to Figure 4: Osteoclasts
spongiotrophoblast formation, which ultimately results
in the formation of trophoblast giant cells. They play an
important role in the implantation of the embryo in the
uterus and help in the exchange of nutrients, wastes, and
gases between maternal and fetal systems.[10]

Pathological giant cells

a
Foreign body giant cells
• Structure: They have numerous nuclei of upto 100–200
with uniform size and shape. They are scattered
throughout the cytoplasm [Figure 5a and b][1]
• Formation: These are formed by the fusion of
macrophages (M2a), are involved in foreign body
response, and cause chronic inflammation and they
require matrix metalloproteinase. They are found at the
tissue‑material interface of implanted medical devices as a
b
foreign body reaction. They are observed in many foreign
body granulomas due to the presence of exogenous and Figure 5: (a) Foreign body giant cell. (b) Histopathological
picture of foreign body giant cells, low power, and high power*
endogenous materials such as silica, suture material, etc.,
also seen in borderline tuberculoid type of leprosy.[6] They
are positive for CD68+, DC‑STAMP+, and E‑cadherin.[8]

Langhans’ giant cell

• Structure: They consist of 15–20 nuclei and arranged on
the periphery of the cell and appear horseshoe‑shaped
or they can be arranged as a cluster at two poles of the
cell formed by the fusion of epithelioid cells. But in
low virulent organisms such as Mycobacterium avium
and Mycobacterium smegmatis have a low number of
nuclei [Figure 6][7]
• Formation: The factors essential for their formation
are interactions of cluster differentiation 40 with its Figure 6: Langhans giant cell
ligand (CD40 L), interferon‑gamma, and dendritic
cell‑specific transmembrane protein. They do not have Aschoff giant cells
phagocytic character but produce interleukins and help • Structure: They are found in Aschoff bodies surrounding
in the granulomatous inflammatory response centres of fibrinoid necrosis, containing more than 4
• Disease associated: Tuberculosis, tuberculoid leprosy, nuclei. These cells have more basophilic cytoplasm in
late syphilis, deep fungal infections, sarcoidosis, contrast to Anitschkow cells
Leishmaniasis, and Crohn’s disease.[6] • Formation: Earlier it was thought to be arising from
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Sreeja, et al.: A review on giant cell lesions of the oral cavity

connective tissue later found that they are derived from giant cells are positive to MIB1 and negative for TRAP[1]
cardiac myocytes • Disease associated: These giant cells are found in many
• Disease associated: Rheumatic heart disease.[11] epithelial and mesenchymal neoplasms like giant cell
tumor of bone.
Touton giant cells
• Structure: These cells have peripheral foamy or
vacuolated eosinophilic cytoplasm with a ring of
nuclei or wreath‑like arrangement in the center.
Touton giant cells are also called Xanthelasmatic giant
cell because of the presence of lipids in the cytoplasm
[Figure 7][1,6]
• Formation: They are formed by the fusion of
lipid‑containing macrophages in the presence of a
factor stimulating lipid uptake. They show positive to
lysozyme, ά1 antitrypsin, CD68, and factor XIIa[8,6]
• Disease associated: Xanthoma, fat necrosis, dermatofibroma,
fibrous histiocytoma, and xanthogranulomas.[6]

Reed–Sternberg cells
• Structure: These cells are different morphologically in Figure 7: Touton giant cell
different clinical types of Hodgkin’s disease.[6] Classic
Reed–Sternberg (RS) cells are large which has bilobed
nucleus appearing as a mirror image of each other
giving owl’s eye appearance, but occasionally can be
multinucleated, coins on the plate appearance seen
in mixed cellularity Hodgkin’s lymphoma. Lacunar
type is smaller with a pericellular lacuna found in the
nodular sclerosis type of HD. Polyphoid types are larger, a
lobulated giving popcorn appearance seen in lymphocyte
predominance type of HD [Figure 8a and b]
• Formation: Immunophenotyping of RS cells reveals
the monoclonal lymphoid origin of RS cells from
B‑cells of the germinal center in most subtypes of
Hodgkin’s disease.[12] RS cells in all types except in
lymphocyte predominance type express immune
reactivity positive for CD15 and CD30, negative for
CD 20 and CD 45 in nodal and extranodal disease. In
lymphocyte predominance type, RS cells are positive b
for CD20 Figure 8: (a) Reed–Sternberg cell. (b) Reed–Sternberg
• Disease associated: These are pathognomonic used cells – Variants in Hodgkin’s lymphoma
in the diagnosis of Hodgkin’s lymphoma, infectious
mononucleosis, and other lymphomas.

Anaplastic tumor giant cells

• Structure: These giant cells contain pleomorphic
nucleus, hyperchromatic, usually diploid showing
abnormal mitosis, and closely resemble mononuclear
tumor population [Figure 9]
• Formation: Tumor cells possess abnormal surface and
they produce extracellular enzymes that might reduce
surface coat thickness, which approximates lipid bilayers
resulting in fusion or passenger viruses seen in some
tumors cause fusion of cells. They are mainly formed
by dividing the nucleus of neoplastic cells. These tumor Figure 9: Tumor giant cells

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Sreeja, et al.: A review on giant cell lesions of the oral cavity

Tzanck giant cells

• Structure: The cell is almost bizarre or atypical in shape.
The nuclei in these cells are crowded together with a
peripheral margin of chromatin condensation and the
nucleus appears like ground glass [Figure 10][6]
• Formation: These cells are epidermal in origin. Viruses
cause abnormal alteration in the epithelial cells and
result in the formation of multinucleated giant cells
• Disease associated: Herpes simplex, varicella and herpes
zoster, and cytomegalovirus.[6]

Melanocyte‑derived starburst giant cells

• Structure: These are multinucleated melanocytes which
appear stellate shape because of the prominent dendritic
process [Figure 11] Figure 10: Tzanck cells
• Disease associated: Diagnostic feature in identifying
lentigo maligna.[6]

Nevus balloon giant cells

• Structure: Balloon cells are altered melanocytes and are
multinucleated giant cells that are larger than normal
nevus cells. They have a clear cytoplasm or sometimes
contain small vacuolated melanin granules formed by
the union of degenerated melanosomes. The nuclei are
small, round, and finely granular [Figure 12][6]
• Formation: This unusual appearance of balloon cells is
probably resulting from the accumulation of protyrosinase
vesicles because of the defect in the synthesis of melanin
granules. These cells showed positive with the colloidal
iron method for acid mucopolysaccharides and were
faintly positive with PAS reaction[13] Figure 11: Starburst giant cells
• Disease associated: Blue nevus, malignant melanoma,
and melanocytic tumor of the eye.

Warthin–Finkeldey giant cells

• Structure: Irregular cell shape with ten or more
nuclei. Both intracytoplasmic and intranuclear
inclusion bodies are present that is composed of viral
nucleoproteins [Figure 13]
• Formation: This increased number of nuclei within the
cell is because of aberrant cleaving. Inactivated virus can
get fused onto the surface of the cell and reduce the cell
coat thickness, so cells come closer and fusion occurs.
Live viruses can penetrate the cell and form viral coded
proteins on the surface that leads to the fusion of cells[1]
• Disease associated: These cells are specific for measles.
Also, noted in lymphoma, Kimura disease, AIDS‑related
Figure 12: Balloon giant cells
lymphoproliferative disease, and lupus erythematosus.

GIANT CELL LESIONS and Callihan in 1974. It is an asymptomatic sessile or

pedunculated nodule with a papillary surface.
Giant cell fibroma • Clinical features: Asymptomatic sessile or pedunculated
Giant cell fibroma is one of the rare fibrous hyperplastic and the surface of the lesion is pebbly
tumors. This lesion was first proposed by Weather • Histopathologic features: These lesions are
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associated with large stellate fibroblasts and multinucleated
giant cells in the loose connective tissue stroma
• Associated giant cell: In this lesion, there is fusion of
atypical fibroblast to form giant cell which contains
numerous cellular microfibrils is visible
• Marker: These giant fibroblasts are positive for vimentin
and negative for CD68[1]
• Treatment: Treatment will be surgical excision.
Recurrence is rare.
Peripheral giant cell granuloma
Earlier, it was called as peripheral giant cell reparative
granuloma. Peripheral giant cell lesions are reactive,
extraosseous (peripheral), and exophytic, occur as a result
of local irritants such as bacterial plaque, calculus, food
retention, chronic infections, irritation, trauma related
to exodontia, poorly finished fillings, poorly fitted dental
prostheses.[14]
• Clinical features: It is a asymptomatic sessile or
pedunculated lesion that appears as a red or reddish-blue
nodular mass
• Radiological features: It shows superficial erosion of
bone with cupping resorption of alveolar bone
• Histopathologic features: It shows proliferation of
multinucleated giant cells within the plump, ovoid, and
spindle‑shaped connective tissue stroma, multinucleated
giant cells with few nuclei or more with sometimes large,
vesicular nuclei. Acute and chronic inflammatory cells
are present with reactive bone formation
• Giant cell associated: There are many multinucleated
giant cells that do not have usual phagocytosis and bone
resorption function[1]
• Marker: They are positive for Ki‑67
• Treatment: Treatment involves local surgical excision.
The recurrence rate is 10%–18%.[13]
Central giant cell granuloma
Central giant cell granuloma was first described by Jaffe
in 1953.[14] This lesion is classified into aggressive and
Figure 13: Warthin–Finkeldey cell
SRM Journal of Research in Dental Sciences | Volume 12 | Issue 1 | January-March 2021
nonaggressive, based on their clinical and radiographic features.
• Clinical features: This lesion is well demarcated varies
from smaller lesion of 4 mm to larger lesion upto 10 cm
• Radiological features: The lesion may vary from an
incidental radiographic lesion of 5mm in size to a 10cm
or more destructive lesion.
• Histopathologic features: Many multinucleated giant cells
in the background of ovoid or spindle‑shaped mesenchymal
stroma with hemosiderin deposition. Focal areas of
osteoid formation are also present[1,14]
• Associated giant cell: Varying number of osteoclasts
like multinucleated giant cells are found that are not
proliferative, but they involve in bone resorption
• Marker: They are positive forCD68+, TRAP+,
V‑ATPase+, Rank +, and carbon anhydrase II+[8]
• Treatment: Treatment involves curettage, surgical excision,
intralesional steroid injections, calcitonin injections, alpha
interferons, IFB2a, and bisphosphonates. The prognosis
is good and the recurrence rate is 11%–49%.[15]
Orofacial granulomatous inflammation
This term was introduced by Wiesenfeld in 1965.
• Clinical features: It includes cheilitis granulomatosa,
facial nerve palsy, with fissured tongue presenting
Melkersson–Rosenthal syndrome
• Histopathologic features: Most of these granulomatous
lesions present as small, noncaseating granuloma with
peripheral epithelioid cells and lymphocytes. In silicone
granulomas, we can find clear spaces that might be
mistaken as lipoblast [Figure 14a and b]
• Giant cell associated: The epithelioid cells in the
granuloma fuse to form multinucleated giant cells
• Marker: They are positive for CD68 histiocyte marker[16]
• Treatment: Topical/intralesional corticosteroids, topical
tacrolimus, radiotherapy, sulfasalazine, methotrexate,
dapsone, etc.
Tuberculosis
Tuberculosis is a specific granulomatous infectious disease
caused by Mycobacterium tuberculosis. It commonly affects
the lungs but also affects the intestines, meninges, bones,
joints, lymph nodes, skin, and other tissues of the body
• Clinical features: Typical oral lesions are chronic painless
ulceration or swelling, non‑healing extraction sockets,
and intrabony mandibular swelling
a b
Figure 14: (a) Histopathological picture of Melkersson and
Rosenthal syndrome*. (b) Histopathological picture of cheilitis
granulomatosis*
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Sreeja, et al.: A review on giant cell lesions of the oral cavity
• Histopathologic features: Central caseous necrosis
and tubercle granuloma formation at the area of
infection with the collection of epithelioid cells,
histiocytes, lymphocytes, and multinucleated Langhans
type of giant cells are found that are indicative of
tuberculosis [Figure 15a and b][1,17]
The diagnosis is confirmed by the presence of acid‑fast
bacilli in the specimen collected, tuberculin skin test,
and molecular techniques like PCR.
• A s s o c i a t e d g i a n t c e l l : C l a s s i c a l l y a c t i v a t e d
macrophages (M1) and Langhans type of giant cell
• Marker: They are positive for CD68+, Langhans‑type
DC‑STAMP. The marker for acute tuberculosis is
CD40+, and for chronic tuberculosis the marker is
myeloid differentiated primary response 88[8]
• Treatment: Eight weeks regimen of isoniazid, rifampicin,
ethambutol, and pyrazinamide. 16 weeks regimen of
isoniazid, rifampicin, and ethambutol.[18]
Leprosy
Leprosy is a chronic granulomatous infection caused by
Mycobacterium leprae. It mainly not only affects skin,
peripheral nerves, upper respiratory tract, eyes, testes, but
also affects muscles, bones, joints.[1,19]
• Clinical features: Hypopigmented patches, partial or
total loss of cutaneous sensation in the affected areas.
Facial paralysis, leonine facies, plantar ulcers, and loss
of fingers and toes
• Histopathologic features: Depending on the immune
reaction, this disease is divided into two – Lepromatous
and Tuberculoid leprosy. Lepromatous leprosy
demonstrates illformed granuloma. The typical
finding is sheets of lymphocytes intermixed with
vacuolated histiocytes known as leprae or Virchow cell
a and cyclophosphamide. Also, antibiotics such as
b protein 2 in 4p16 chromosome.[23] This mutation results in
Figure 15: (a) Tuberculoid granuloma. (b) Histopathological
picture of tuberculoid granuloma in low power and high power*
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and numerous organisms are evident and tuberculoid
leprosy is where there is a paucity of organisms, shows
tubercles composed of epithelioid cells, Langhans giant
cells, histiocytes, and lymphocytes[1]
• Associated giant cell: Langhans type of giant cells can
be variably present
• Marker: They show positivity for CD68
• Treatment: Patients with multibacillary leprosy receive
rifampicin, dapsone, and clofazimine, and patients with
paucibacillary leprosy receive rifampicin and dapsone.[20]
Syphilis
Chronic infectious disease caused by Treponema pallidum. It
can be acquired or congenital. Acquired syphilis manifests
in three stages, primary, secondary, and tertiary.[21]
• Clinical features: Primary characterized by solitary or
multiple chancre. Secondary syphilis shows diffuse
mucocutaneous eruptions. Tertiary syphilis manifests
as gumma which occurs on the tongue and hard palate
• Histopathologic features: Gumma consists of
central coagulative necrosis surrounded by palisaded
macrophages. The surface epithelium is ulcerated
and underlying connective tissue shows chronic
inflammatory cells with predominantly of lymphocytes
and plasma cells, immunoperoxidase reaction shows
corkscrew‑like spirochetal organism in the epithelium
• Treatment: For primary and secondary stages, single
intramuscular dose of long‑acting benzathine penicillin
G is given. For the tertiary stage, intramuscular penicillin
G is administered for 3 weeks.[21]
Wegeners granulomatosis
It is an abnormal immune response to nonspecific infection
or aberrant hypersensitive response to inhaled antigen or
infectious agent involves vascular, renal, and respiratory
system.
• Clinical features: Strawberry gingivitis, diffuse ulcerative
stomatitis, spontaneous exfoliation of teeth, and failure
of tooth sockets to heal after extraction
• Histopathologic features: Mixed inflammation around
blood vessel, heavy neutrophilic infiltration and necrosis,
and leukocytoclastic vasculitis. Connective tissue
shows the collection of epithelioid cells, histiocytes,
lymphocytes, and multinucleated giant cells[22]
• Treatment: This lesion can be treated with prednisolone
sulfamethoxazole and trimethoprim are successful in
localized cases.
Cherubism
It is a rare genetic disease affecting the jawbones of children,
introduced by Jones in 1933. They have an autosomal
dominant triat with mutations in SH3domainbinding
the differentiation of osteoclast progenitor cells, resulting in
hyperactive osteoclasts produce lytic bone lesion
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Sreeja, et al.: A review on giant cell lesions of the oral cavity
• Clinical features: Painless, bilateral symmetrical
enlargement of the maxilla and mandible
• Radiological features: It shows bilateral, multilocular,
and expansile root resorption and thinning of cortical
bone of jaws
• Histopathologic features: It shows vascular fibrous
stroma with numerous multinucleated giant cells with
hemorrhage. The most specific feature is eosinophilic
cuffing around the blood vessels
• Associated giant cell: Osteoclast like multinucleated
giant cells in cherubism differentiates into macrophages
in nonaggressive and osteoclasts in aggressive type
• Marker: They are positive for CD68+, TRAP+,
V‑ATPase+, cathepsin K+, and carbon anhydrase II+[14]
• Treatment: Cherubism regresses gradually after puberty.
Partial or complete surgical resection can be done in
aggressive lesions.[23]
Fibrous dysplasia
A developmental tumor‑like condition characterized by
replacement of bone by the recessive proliferation of cellular
fibrous connective tissue intermixed with irregular bony
trabeculae. It is caused due to postzygotic mutation of GNAS1.[24]
• Clinical features: Two types: Monostotic and polyostotic,
with typical leonine facies
• Radiological features: Healthy bone is replaced by
more radiolucent bone with thick sclerotic border and
is called rind sign. Early lesions show unilocular or
multilocular radiolucencies, whereas mature lesions
show radiopaque spicules giving ground glass or orange
peel appearance
• Histopathologic features: Fibrous connective tissue
stroma contains irregular bony trabeculae. The bony
trabeculae are curvilinear shaped– Chinese letter pattern
and osteoblastic rimming is absent
• Associated giant cell: Osteoclast like giant cell
• Markers: They are positive for CD45, CD68+, TRAP+,
V‑ATPase+, Rank +, and carbon anhydrase II+
• Treatment: Conservative treatment. Larger lesion
surgical contouring is done.
Pagets disease
Chronic progressive disease of bone named after the British
surgeon Sir James Paget in 1877 who first described it
as “OsteitisDeformans”. The disease is characterized by
abnormal resorption and deposition of bone resulting in
distortion and weakening of affected bone. Inflammatory,
genetic, paramyxovirus could be reasoned out but the exact
cause is unknown. The increased bone resorption is due to
the increased Vitamin‑D receptor binding affinity among
osteoclasts leading to increased osteoclastogenesis is seen.[25]
• Clinical features: Asymptomatic, sometimes presents
with bony pain, bone deformity, musculoskeletal and
cardiovascular anomalies
• Radiological features: Earlier lesions show osteoclastic
phase, destructive radiolucent areas are seen, followed
SRM Journal of Research in Dental Sciences | Volume 12 | Issue 1 | January-March 2021
by mixed osteoclastic and osteoblastic phase that
shows patchy radiolucent areas. Finally, more of bone
formation, the osteoblastic phase is seen that gives
cotton wool appearance
• Histopathologic features: There are numerous
multinucleated giant cells resembling osteoclasts.
Surrounding bony trabeculae showing resorption and
a highly vascular connective tissue stroma replace the
marrow. Osteoblastic rimming is present. Basophilic
resting and reversal lines give “jigsaw puzzle or mosaic”
appearance of bone
• Associated giant cell: Osteoclast like giant cell
• Marker: They are positive for CD45, CD68+, TRAP+,
V‑ATPase+, Rank +, and carbon anhydrase II+
• Treatment: Treatment involves bisphosphonate therapy,
single infusion of zoledronic acid, and oral risedronate
administered daily for several months.
Giant cell tumor
Cooper first reported it in the 18th century. Jaffe and
Lichtenstein defined it as giant cell tumor in 1940. This is
considered to occur, de novo but also as a complication of
Paget’s disease.
• Clinical features: Extragnathic giant cell tumors are
symptomatic unlike giant cell lesions of jaws
• Histopathologic features: Multinucleated giant cells and
spindle‑shaped mononuclear cells are seen. There is a
similarity in the size of nuclei of MGC and connective
tissue stroma contains little collagen and marked
hemorrhage. Giant cells are diffuse or focally clustered
with typical mitotic figures[1]
Histomorphometric study on GCT and GCG found that
statistically significant difference between the two lesions
with regard to stromal cellularity, even distribution of GC,
number of nuclei, presence of tumor necrosis, presence of
inflammatory cells [Figure 16].
• Associated giant cell: Osteoclast‑like giant cells
• Marker: They are positive for CD45, CD68+, TRAP+,
V‑ATPase+, Rank +, and carbon anhydrase II+[8]
• Treatment: Treatment involves simple or aggressive
curettage and tumor resection and reconstruction. Low
recurrence rate.[1]
Figure 16: Histopathological picture of giant cell tumor of
tendon sheath low power and high power*
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Sreeja, et al.: A review on giant cell lesions of the oral cavity
CONCLUSION
Giant cells are important recognizable cells in histopathology,
that aids in the diagnosis of a disease, or it can function as a
reactive cell to remove or eliminate the pathogen involved in
the disease. Many authors have given different approaches to
classify these giant cells, all of which help the pathologist by
giving a hint to diagnose and for proper treatment planning.
To emphasize new, in this article, we have provided basic
information about the clinical, radiological, histopathological
features, and treatment planning of various giant cell lesions,
the information about giant cells and giant cell lesions are
very useful diagnostic tool for the physicians, clear cut
histochemical markers also give a clue for pathologists in
diagnosing such lesions.
Acknowledgement
*Histopathologic pictures were collected from Chettinad
Dental College and Research Institute and Chettinad
Hospital and Research Institute Kelambakkam, Chennai.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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