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 Table of Contents  
Year : 2021  |  Volume : 12  |  Issue : 1  |  Page : 27-36

Giant cell lesions of the oral cavity

1 Departments of Oral and Maxillofacial Pathology, Chettinad Dental College and Research Institute, Kelambakkam, Chennai, Tamil Nadu, India
2 Department of General Pathology, Chettinad Hospital and Research Institute, Kelambakkam, Chennai, Tamil Nadu, India

Date of Submission11-Oct-2020
Date of Decision23-Dec-2020
Date of Acceptance13-Jan-2021
Date of Web Publication30-Mar-2021

Correspondence Address:
Dr. Sreeja Chellaswamy
Department of Oral and Maxillofacial Pathology, Chettinad Dental College and Research Institute, Kelambakkam, Chennai - 603 103, Tamil Nadu
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DOI: 10.4103/srmjrds.srmjrds_106_20

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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.

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

How to cite this article:
Chellaswamy S, Manohar P, Rajakumari B, Ramalingam SM, Ragavan V, Nachiappan N. Giant cell lesions of the oral cavity. SRM J Res Dent Sci 2021;12:27-36

How to cite this URL:
Chellaswamy S, Manohar P, Rajakumari B, Ramalingam SM, Ragavan V, Nachiappan N. Giant cell lesions of the oral cavity. SRM J Res Dent Sci [serial online] 2021 [cited 2021 Jun 25];12:27-36. Available from:

  Introduction Top

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

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] based on pathognomonic and nonpathognomonic association [Table 3], and[4],[5] based on origin in the form of flowchart [Figure 1].[6]
Table 1: Classification of giant cells based on their functional characteristics

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Table 2: Classification of giant cell lesions based on etiopathogenesis

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Table 3: Classification of giant cell lesions based on the etiopathogenesis, with pathognomonic and nonpathognomonic association

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

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  Formation of Giant Cell Top

Monocytes or macrophages are leukocytes which functions as a phagocytic cell and aids in the removal of the pathogenic antigens and foreign materials from the body. They are large mononucleated cells that play an important role in innate as well as acquired immunity. They are involved commonly in the chronic inflammation and sometimes in the later stage of acute inflammation. The important function of these cells is to remove the pathogenic antigens or foreign material from the body, when the individual macrophages are unable to remove the foreign particles they join or fuse together to form large multinucleated giant cells.[7] There are a series of steps involved in the giant cell formation, which include recognition, adhesion, fusion, and activation.

The fusion of the macrophages was described by different authors and various theories were put forth. There are a few proposed mechanism by Singer and Nicolson, 1872 – the lipid bilayer present in the cell wall is responsible for the attachment between two cells and Heine and Schnaitman, 1971 – direct interaction between the viral envelop and cell surface in which antigens from the viral envelop gets incorporated into the polykaryon membrane, which forms the bridge between two cells resulting in fusion.[8]

The two theories of giant cell formation are;

  1. Nuclear division of monocytes with the absence of cytoplasmic division
  2. Fusion between monocytes.

These theories were explained by experiments conducted by Forkner in 1930 – two giant cells were formed in which one showed a rosette pattern of nuclear arrangement at the periphery (Langhans type) and other showed an irregular arrangement of nuclei (foreign body type), from this he stated that peripheral arrangement of nuclei can be due to nuclear division of monocytes and the irregular pattern can be due to fusion of monocytes [Figure 2].[3]
Figure 2: Formation of giant cells

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Concepts on the fusion of giant cells;

  1. Immune-mediated concept – lymphokines and cell surface changes facilitate fusion of macrophages
  2. Young and old macrophage concept – recognition of old macrophages, which shows chromosomal abnormality and altered cell surface which stimulates the fusion process between old and young macrophages
  3. Endocytic activity concept – two or more macrophages try to ingest or engulf the same antigen the resulting phagocytosis causes fusion of endosome margins between two cells.[1]

  Types of Giant Cells Top

Physiological giant cells


  • Structure: They are large polypoidal cells present in the bone marrow. It has a multinucleated or multilobed nucleus with the presence of prominent cytoplasm and azurophilic granules [Figure 3]
  • Formation: Megakaryocytes are physiological giant cells arising from hematopoietic stem cells. They undergo multiple endocytosis leading to the formation of multinucleate giant cell. These are platelet precursors involved in platelet formation.[9]
Figure 3: Megakaryocytes

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  • Structure: They morphologically resemble foreign body giant cells but have less number of nuclei, usually each cell has 10–20 nuclei present on the endosteal surfaces within the Haversian system of bone [Figure 4]
  • Formation: they are terminally differentiated multinucleated cells which originate from the mononuclear cells of the hematopoietic stem cell lineage. Two cytokines are involved in the formation of osteoclasts, namely Receptor Activator of Nuclear Factor Kappa 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]
Figure 4: Osteoclasts

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  • 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 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

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 5]a and [Figure 5]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 foreign body reaction. They are observed in many foreign body granulomas due to the presence of exogenous and 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]
Figure 5: (a) Foreign body giant cell. (b) Histopathological picture of foreign body giant cells, low power, and high power*

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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 ligand (CD40 L), interferon-gamma, and dendritic cell-specific transmembrane protein. They do not have phagocytic character but produce interleukins and help in the granulomatous inflammatory response
  • Disease associated: Tuberculosis, tuberculoid leprosy, late syphilis, deep fungal infections, sarcoidosis, Leishmaniasis, and Crohn's disease.[6]
Figure 6: Langhans giant cell

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Aschoff giant cells

  • Structure: They are found in Aschoff bodies surrounding centres of fibrinoid necrosis, containing more than 4 nuclei. These cells have more basophilic cytoplasm in contrast to Anitschkow cells
  • Formation: Earlier it was thought to be arising from connective tissue later found that they are derived from cardiac myocytes
  • Disease associated: Rheumatic heart disease.[11]

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]
Figure 7: Touton giant cell

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Reed–Sternberg cells

  • Structure: These cells are different morphologically in 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, lobulated giving popcorn appearance seen in lymphocyte predominance type of HD [Figure 8]a and [Figure 8]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 for CD20
  • Disease associated: These are pathognomonic used in the diagnosis of Hodgkin's lymphoma, infectious mononucleosis, and other lymphomas.
Figure 8: (a) Reed–Sternberg cell. (b) Reed–Sternberg cells – Variants in Hodgkin's lymphoma

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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 giant cells are positive to MIB1 and negative for TRAP[1]
  • Disease associated: These giant cells are found in many epithelial and mesenchymal neoplasms like giant cell tumor of bone.
Figure 9: Tumor giant cells

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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]
Figure 10: Tzanck cells

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Melanocyte-derived starburst giant cells

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

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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]
  • Disease associated: Blue nevus, malignant melanoma, and melanocytic tumor of the eye.
Figure 12: Balloon giant cells

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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 lymphoproliferative disease, and lupus erythematosus.
Figure 13: Warthin–Finkeldey cell

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  Giant Cell Lesions Top

Giant cell fibroma

Giant cell fibroma is one of the rare fibrous hyperplastic tumors. This lesion was first proposed by Weather and Callihan in 1974. It is an asymptomatic sessile or pedunculated nodule with a papillary surface.

  • Clinical features: Asymptomatic sessile or pedunculated and the surface of the lesion is pebbly
  • Histopathologic features: These lesions are 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 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 14]a and [Figure 14]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.
Figure 14: (a) Histopathological picture of Melkersson and Rosenthal syndrome*. (b) Histopathological picture of cheilitis granulomatosis*

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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
  • 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 15]a and [Figure 15]b[1],[17]
  • Figure 15: (a) Tuberculoid granuloma. (b) Histopathological picture of tuberculoid granuloma in low power and high power*

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    The diagnosis is confirmed by the presence of acid-fast bacilli in the specimen collected, tuberculin skin test, and molecular techniques like PCR.

  • Associated giant cell: Classically activated 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 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 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]


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 and cyclophosphamide. Also, antibiotics such as sulfamethoxazole and trimethoprim are successful in localized cases.


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 protein 2 in 4p16 chromosome.[23] This mutation results in the differentiation of osteoclast progenitor cells, resulting in hyperactive osteoclasts produce lytic bone lesion

  • 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 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].
Figure 16: Histopathological picture of giant cell tumor of tendon sheath low power and high power*

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  • 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]

  Conclusion Top

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.


*Histopathologic pictures were collected from Chettinad Dental College and Research Institute and Chettinad Hospital and Research Institute Kelambakkam, Chennai.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16]

  [Table 1], [Table 2], [Table 3]


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