giant cell lesions of the maxillofacial area can vary from asymptomatic radiolucency of slowly growing lesion to aggressive tumours showing high recurrence rate as well as rapid expansive progression characterized by root resorption and pain .
gcgs of the jaws arise either peripherally in periodontal ligament , mucoperiosteum , or centrally in the bone .
the world health organization has defined the central giant cell granuloma as an intraosseous lesion consisting of cellular fibrous tissue that contains multiple foci of hemorrhage , aggregations of multinucleated giant cells and occasionally trabeculae of woven bone .
histologically , both peripheral and central variants of giant cell granuloma are characterized by the presence of numerous multinucleated giant cells ( mgcs ) in a prominent fibrous stroma .
foci of hemorrhage with liberation of hemosiderin pigment and newly formed osteoid or bone are often seen .
the mgcs are concentrated in the areas of hemorrhage and are adjacent to blood vessels .
jaffe separated cgcg from gct of the bone on clinical and histologic grounds and suggested that mgcs in cgcg represent a phagocytic response to hemorrhage .
however , it affects females more often than males , in a 2:1 ratio and is seen most frequently under the age of 30 years .
one study of 38 patients shows 74% to be less than 30 years of age and 61% to be less than 20 years of age .
the lesion commonly presents as a solitary radiolucency with a multilocular appearance or less commonly , a unilocular appearance .
it is more prevalent in the anterior than the posterior jaws , often crossing the midline , and the mandible is more commonly affected than the maxilla .
this lesion has also been reported in the small bones of the hands and feet .
the behavior of cgcg is variable , most commonly producing an asymptomatic expansion of the jaws .
however , it can be clinically aggressive , associated with pain , osseous destruction , cortical perforation , root resorption , and recurrence
. cases of cgcg occurring with neurofibromatosis ( type 1 ) , noonan - like syndrome , or both have been reported .
these lesions may possibly lead to a confusion in their correct diagnosis as many pathologists report them taking into consideration one of the prominent histopathologic feature .
such misinterpretation may be because of the small number of cases reported in the literature with uncertain clinical , radiographic and histopathologic features of these lesions .
so even surgeons may end up treating these lesions inadequately or patients may need to undergo multiple surgeries .
the present case report highlights a case of recurrent and aggressive form of cgcg in the mandible .
a 22-year - old man presented with a swelling in the left ramus of the jaw 2 years ago .
examination revealed a unilocular radiolucent lesion , with a scalloped inferior border [ figure 1 ] .
the ct scan revealed a well defined hyperdense soft tissue seen in the region of and below the left coronoid process of mandible , with suspicion of sclerosis .
a partial mandibulectomy was performed and a reconstruction plate with a mini plate at the anterior region along with a fibular graft in the jaw was inserted to repair the defect [ figure 2 ] .
the inferior border of the lesion is scalloped orthopantomograph showing the reconstruction plate repairing the defect in the left jaw after one year , the patient , now 23 years old , complained of a recurrent swelling in the same region .
intraorally , the patient presented with a growth in the left buccal mucosa at the level of the occlusal plane , which was excised and microscopically reviewed .
the first molar along with the premolars were removed , the region was curetted and a new reconstruction plate was given .
photomicrograph confirming the presence of granulomatous lesion ( h and e , 40 ) a year later , the patient now 24 years old , was referred to the department of oral surgery with the complaint of pain and recurrent swelling of the left jaw [ figure 4 ] .
extra oral swelling of the left lower jaw clinically the lesion extended from the corner of the mouth to the anterior part of tragus on the left side , which was 4  4 cm in size , irregular in shape with a rough texture .
the swelling was hard in consistency , showed no secondary changes and was non tender on palpation .
intraoral examination revealed an exophytic growth present posteriorly near the junction of the buccal mucosa and pterygomandibular fossa region , at the level of the occlusal plane , sized 1  1.5 cm and soft in consistency .
presently the ct scan revealed an evidence of an expansile destructive mass ( 4.3  3.8  4.3 cm in the maximum anteroposterior , transverse and superoinferior dimensions ) in the expected location of the left coronoid process , with thin residual septae like areas of osseous density seen in a large soft tissue mass .
this soft tissue mass showed near isodensity compared to the adjacent muscles of the left masseteric space .
the lesion expanded the insertion of the left temporalis muscle and bulged anteriorly into the left buccal space and posteriorly into the left condylar head and neck and left parotid gland .
medially , the lesion led to mild pressure erosion with thinning of the buccal cortex of the left maxillary tuberosity and bulged against the left medial pterygoid muscle [ figure 6 ] .
intra oral photograph depicting exophytic growth in the junction of the left pterygomandibular fossa region and buccal mucosa ct scan showing the extent of the lesion during the second recurrence routine hemogram and urine examination were normal .
on the basis of clinical and radiological examination a provisional diagnosis of cgcg was made .
the serum chemistry of calcium , phosphorous , parathyroid hormone was normal , there by excluding the possibility of hyperparathyroidism .
surgery was performed by a submandibular incision at the site of the previous scar , with the removal of the reconstruction plate , mini plate and graft , along with the condyloid process .
histopathological examination of excised specimen revealed evenly dispersed ( 2 - 3/hpf ) giant cells each having 2 - 8 nuclei in them , in close approximation with proliferating blood vessels admixed with areas of haemorrhage .
even the bone graft attached to the condyle showed the presence of tumor giant cells [ figure 8 ] .
no recurrence was noticed in post operative follow - up phase of 3 years [ figures 9 and 10 ] and further reconstruction of mandible using iliac crest graft is intended .
photomicrograph showing giant cells in a vesiculated fibroblast connective tissue stroma ( h and e , 40 ) photomicrograph showing presence of giant cells near the condylar region ( h and e , 40 ) post - operative follow up opg verifying the absence of lesion post - operative intraoral view
the etiopathogenesis of the cgcg of jawbones has not been clearly established but it has been suggested that it is the result of an exacerbated reparative process related to previous trauma and intraosseous hemorrhage that triggers the reactive granulomatous process .
donoff and rosenberg discussed a case record of an uncomplicated extraction because of pericoronitis in the area of the lesion and claimed the local changes in the blood flow throughout the bone and local bone dysplasia could be probable etiologic factors .
unal et al . , presented a 12-year - old girl cgcg in the mandible caused by a molar tooth extraction and explained the pathogenesis by a traumatic aetiology .
association of t ( x ; 4)(q22;q31.3 ) in the etiology of gcg has been reported .
although , cgcgs are benign osseous lesions , some authors separate cgcg into two types , referring to its clinical and radiographic features : ( a ) nonaggressive lesion is usually slow growing and asymptomatic , does not show cortical resorption by the lesion or root perforation in teeth affected , and it is significantly less likely to recur than the aggressive type ; and ( b ) aggressive lesions , is usually found in younger patients and is painful , grows rapidly , is larger , often causes cortical perforation and root resorption and has a tendency to recur .
predicting the behavior of cgcgs that will exhibit a higher risk of recurrence after treatment has been problematic .
waldron reported a mean interval between diagnosis and initial treatment and treatment of a recurrence was 21 months , and stated that very few recurrences were manifested after 2 years of initial treatment .
the most reliable factors related to an increased risk of recurrence include clinical activity of lesions ( 72% of recurrence in the aggressive forms , 3% of recurrence in the nonaggressive forms ) , younger patients , demonstrated perforation of cortical bone and tumor size
. there has been studies suggesting that the greater functional surface area occupied by giant cells and larger relative size of giant cells may identify tumors with aggressive behavior .
recently , kruse - loser et al . , also proved that the aggressive variant of cgcg presented a high number of giant cells , an increased mitotic activity , and a high fractional surface area .
however , other studies have not been able to predict the clinical course of cgcgs from known histological or immunohistochemical features .
we reviewed the archival cases of 10 cgcgs from our department which were nonaggressive and non recurrent , the demographical information , location , radiographic features and histopathological features of which are shown in table 1 .
the demographic information , location , radiographic features and histopathological features of 10 nonaggressive cgcgs are as follows the present case showed 2 - 3 giant cells per high power field , which was less compared to that seen in our archival cases .
the connective tissue was minimal , but with a high cellularity and a vesiculated fibroblast population .
the nonaggressive cases of cgcg showed a minimal - moderate cellularity and a non vesiculated fibroblast population .
the vascularity in the present case was minimal , which was not a differentiating factor , as cases in the archives showed a varied vascularity from minimal to marked .
. it may be well - defined or ill - defined and shows variable expansion and destruction of the cortical plate .
the radiological appearance of the lesion is not pathognomonic and may be confused with that of many other lesions of jaws .
the final diagnosis eventually rests on histopathology because the clinical and radiological features are not specific .
cgcg of the jaw usually presents as a painless solitary radiolucent expansion in most of the cases .
rankl ( receptor activator of nuclear factor kb ligand ) present on stromal cells influences the differentiation of giant cells from rank expressing mononuclear cells . amongst all , gct is most difficult to differentiate from cgcg without clinical and histological aids .
histologically , cgcg has a hemorrhagic background with presence of plump bland fibroblast , hemosiderin and fewer giant cells with smaller number of nuclei , which are less uniformly distributed . while in case of gct , giant cells are uniformly scattered with larger number of nuclei and absence of fibroblasts and hemorrhage .
diffuse sheets of large giant cells and polygonal mononuclear cells seen in gct are lacking in cgcg .
cystic areas ( the aneurysmal bone cyst component ) are lesser as compared to gct .
differential diagnosis from brown tumor is based mainly on clinical and laboratory data , as well as age of onset and multiplicity of lesions .
immunohistochemical studies on cgcg have helped to establish the lineage of the cells , but not to predict the aggressiveness of the lesion .
supporting the theory that the multinucleated giant cells are derived from macrophages is the immunoreactive response to muramidase , -1antichymotrypsin , and -1antitrypsin .
aggressive and nonaggressive cgcgs stained for antibodies to cd34 , cd68 , factor xllla , and smooth muscle actin , prolyl 4-hydroxylase , ki-67 , p53 protein , rank , and glucocorticoid receptor alpha have revealed no phenotypic differences between the types .
calcitonin receptor expression , however , has been found to exhibit a statistically significant difference with more expression in the aggressive type .
generally , curettage of well - defined localized lesions is associated with a low rate of recurrence . in extensive lesions with radiographic evidence of perforation of cortex ,
the medical management of cgcg as an adjunct to surgery includes treatment with steroids or calcitonin which inhibits osteoclastic activity .
interferon - alpha appears useful in the management of aggressive cgcg , presumably due to its anti - angiogenic effects .
although extensive literature has been made available to the readers who envisage a keen interest in cgcg of the jaw , clarity to this entity with respect to terminology , behavior and its adjunctive nature to the gct occurring in long bones has rarely been lucid in its understanding . the concomitant presence or initiation of this entity with various other diseases like aneurysmal bone cyst and also its histopathological similarities to diseases associated with hormonal imbalances like
the present case highlights the perplexity in diagnosing cgcgs , which are aggressive in nature due to its close proximity with respect to pathology , behavior and prognosis from gct .
the recurrent nature of the present case and the extensive destruction caused in the hard and soft tissues convinces us the need of exploring the possibilities of the so called true 
 central giant cell granuloma is a fairly common lesion in the jaws aetiology of which is still completely unknown but thought to be of a reactive process to some unknown stimuli . 
 it usually arises either peripherally in periodontal ligament , mucoperiosteum , or centrally in the bone . 
 the histological hallmark for both peripheral and central giant cell granuloma ( cgcg ) is the presence of distinctive multinucleated giant cells ( mgcs ) in a prominent fibrous stroma . 
 central giant cell granuloma is an uncommon benign proliferative lesion that almost exclusively occurs within the jaw . 
 eventually , it may become aggressive leading to the expansion and perforation of cortex resulting into mobility and displacement of teeth with root resorption . 
 the present case focuses on the dilemma and perplexity in diagnosing aggressive cgcgs , due to its close proximity with respect to pathology , behavior and prognosis from giant cell tumors ( gct ) . 
 central giant cell granuloma persuaded extensive destruction to the hard and soft tissues with high rate of recurrence encourage us the need of exploring the possibilities of giant cell tumors having a definitive presence in the jaws . 
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