Aggressive Central Giant Cell Granuloma – Five Cases With Review

Abstract

Central Giant Cell Granuloma (CGCG)of the maxillofacial region generally present as an asymptomatic slowly growing localised disease to aggressive neoplasm like rapid expansive progression typically present with localised disease. It is an uncommon benign lesion with a low incidence that occurs in the craniofacial region especially in jaw bones. It is a localised osteolytic lesion with varied biologic behavior of aggression which affects the jaw bones. There is much controversy regarding it arising as a result of trauma and its connection with the giant cell lesion seen in the long bones. As it is uncommon, it does not possess any characteristic clinical or radiologic features, and resembles neoplasms, the diagnosis is initially some odontogenic or non- odontogenic neoplasm till a definitive histologic diagnosis of CGCG is made. In this article, we sought to report five cases of aggressive form of CGCG with different sites of involvement of the lesion.

KEY WORDS: giant cells, multilocular radiolucency, calcitonin, granuloma

Introduction

Central giant cell granuloma (CGCG) is an uncommon benign but sometimes aggressive, osteolytic proliferation consisting of fibrous tissue with hemorrhage and hemosiderin deposits and presence of osteoclast like giant cells with reactive bone formation. Etiopathogenesis is not known but bone haemorrhage from past trauma has been suggested as a probable cause. Some considered it to be a reactive lesion to an unknown stimulus and some to a neoplastic lesion. Peak incidence is in the second decade and more common in female. Most common site is anterior to mandibular first molar and often crosses the midline. Radiographically well-defined uni/multilocular radiolucency is seen with lesions. Patients typically present with localised disease that has an insidious natural clinical course, with solitary lesions identified incidentally.

CASE NO. 1 A 24 yr old female patient reported with pain and swelling in the right back region since two months. No history of trauma was reported. On extra oral examination,a swelling was seen on the right side of the face extending from outer canthus of eye to lower border of mandible superior-inferiorly and anterio-posteriorly from the corner of mouth to angle of mandible, measuring approx. 5x4cm. The overlying skin was normal in color with no signs of bleeding or ulceration. On palpation, swelling was non-tender,firm in consistency. On intra-oral examination a single large growth was seen involving the upper and lower right posterior vestibular mucosa, attached gingiva, extending from distal aspect of 26 to 1cm beyond the pterygopalatine raphe and superior-inferiorly from upper buccal vestibule to lower buccal vestibule measuring approx 3x 4cm in size obliterating both the upper /lower vestibular mucosa. The overlying surface was irregular, bright red and ulcerated. Lingual tilt with 46, 47 was seen. On palpation the growth was tender, firm in consistency. It is non-fluctuant, non-compressible and non-pulsatile. Radiographically, CT showed a well-defined expansile multilocular lytic lesion measuring 5. 6 cm in mediolateral dimension, 4. 3cm in anteroposterior dimension and 5 cm in cranio caudal dimension, involving the right angle of mandible and coronoid process with enhancing soft tissue mass. Also, thinning and breach in the overlying cortex was seen.

CASE NO. 2A 26 year old female patient reported with a swelling in the upper left back region of the jaw since one month. She gave history of extraction of upper left mobile tooth after which the swelling appeared. Swelling was painful and initially was smaller in size which increased to the present size. The pain associated with swelling was dull and intermittent. On extraoral examination,no facial asymmetry was seen. On intraoral examination, a well defined swelling was seen involving the upper left posterior vestibular mucosa, attached gingiva, alveolar mucosa and palatal mucosa with respect to 24-27 with obliteration of buccal vestibule. On palpation, swelling was tender and firm in consistency. There was grade II mobility with 24,25,27,28. Radiologically on CT, a well defined mass evident in upper left maxilla with partial obliteration of left maxillary sinus and destruction of floor, medial and lateral wall of maxillary sinus.

CASE NO. 3 A 24 yr old male patient reported with a swelling in his lower front region of jaw since 25 days. He gave history of trauma 5yrs back. Swelling was small in size and enlarged to the present size and was associated with pain, following a trauma 25 days back. On examination, facial asymmetry was present. A diffuse swelling was seen extending superioinferiorly from lower lip to about 2cm below the anterior lower border of the mandible and mediolaterally from right corner of the mouth to left corner of the mouth. Intraoral examination revealed a diffuse swelling in region of mandible extending from 36 on the left side, crossing the midline up to 46 on the right side. The swelling was extending to involve the labial and lingual mucosa. On palpation the swelling was tender and firm in consistency. There was displacement of lower anterior teeth i. e, 31,32,41,42 were labially tilted whereas 33, 34, 35, 36, 43, 44, 45, 46 were lingually tilted(fig 8). Radiographically, CT scan demonstrates a lytic lesion within the mandible in the antero-posterior direction with erosion of buccal cortex of the mandible(Fig 9a and 9b). CASE NO. 4A 58 yr old male patient reported with the swelling in the upper front region of jaw since 3 months. He gave a history of pain since 2 months. No history of trauma was reported. On extraoral examination, a swelling was seen in relation to the upper lip. On intraoral examination a diffuse swelling was seen in the upper anterior region extending from 11-24 regions with obliteration of labial vestibule. Overlying mucosa was normal. Swelling was tender and firm in consistency. Displacement with 21, 22 and 23 was seen. Radiographically on CBCT, an ill defined expansile osteolytic defect was seen in the maxillary anterior region with partial loss of buccal cortication. Haziness in the left maxillary sinus was seen.

CASE NO. 5A 27 year old female patient reported with pain in the lower front region of jaw since 4 years. She also noticed a nodular swelling on the inner side of her lower front teeth. She underwent surgical excision of the lesion along with surrounding bone and the histopathological diagnosis was CGCG. Three months prior to reporting, she again noticed a similar nodular swelling in the lower left anterior region of the jaw. On extraoral examination, no facial asymmetry was seen. On intraoral examination, the swelling extends from 33 to 35 lingually. Overlying mucosa is bluish red with few haemorrhagic spots. On palpation, swelling was firm superiorly and hard inferiorly and associated with mild tenderness. Missing teeth were 31, 32, 41,42,43,44,45 and grade II mobility with 33,34 was seen. Lingual tilting of 33,35 was present. On CT examination, an expansile, multiloculated lytic lesion was present in the left side of mandible involving the sympysis menti. Associated enhancing soft tissue seen within the lesion. Bicortical expansion was also present. After correlating the findings, a provisional diagnosis of benign odontogenic cyst/tumor was made for all cases. Blood investigations such as serum calcium, serum Phosperous, serum alkaline phosphatase were carried out which were within the normal limit for all the cases. On histopathological examination, all the above cases were found to be central giant cell granuloma. The above cases were treated as follows: the first three cases were managed with enbloc resection, whereas the other two were managed with surgical curettage.

Discussion

CGCG was first described by Jaffe in 1953. CGCG is considered to be reparative and reactive in nature. It is not considered to be a benign neoplasm. Jaffe coined the term ‘Giant cell reparative granuloma. ’ However the word ‘Reparative’ has been removed since the condition is not reparative in nature. The WHO has defined it as an intra-osseous lesion consisting of cellular fibrous tissue that contains multiple foci of haemorrhage, aggregations of multinucleated giant cells and occasionally trabeculae of woven bone. CGCG is bony lesion mainly affecting adolescence and young preferably younger than 20 yrs and involves mandible more than maxilla, predominantly the region anterior to the 1st molar in the mandible and anterior to cuspids in the maxilla. Some believed CGCG to be related to the teeth in some way, though they were not truly thought to be an odontogenic lesion. The giant cells involved in the lesion may have been derived from the odontoclasts which led to resorbtion of the deciduous teeth.

This might explain why they were found in a certain age group and generally found in areas of the jaws that had previously held deciduous teeth. In our series, all patients were young; expect one who was a 58 yr old male patient. The oldest reported case in literature was a 94 yr old patient.

The F: M ratio was 3:2 as seen in literature wherein females are more commonly affected. The presented cases here had a different site of occurrence of the lesion i. e, in two patients maxilla was involved (1-anterior, 1-posterior) and in two patients mandible was involved (1-anterior, 1-posterior) and in one patient the lesion was crossing the midline in the mandible. The epicenter is usually anterior to first molar in young patients but there is a tendency for the epicenter to occur in the posterior region of the jaws after the first 2 decades of life. Whereas in our case series,one patient who was an 58 yr old patient had the lesion in the anterior region of maxilla which is not in accordance with studies in the literature. The most common presenting sign is a pain less swelling whereas, all the cases presented here had presence of pain associated with swelling. Few may complain of pain, paresthesia and displacement of teeth.

The swelling may cause facial asymmetry and difficulty in mastication. The radiographic appearance of the lesion can be unilocular/multilocular. Because it is a slow growing lesion, it produces a well defined margin. In our case series all the cases showed well defined margins expect one that was seen in a 58 yr old male patient wherein the margins were ill defined. The internal structure may show granular pattern of calcification which is organised into ill defined, wispy septa which emanate at right angles to the periphery of the region. The aggressive forms of CGCG may displace anatomical structures like teeth,mandibular canal and floor of maxillary antrum.

All cases showed tooth displacement and two cases involved the maxillary antrum. CGCG must be differentiated from aneursymal bone cyst (ABC), OKC and unicystic ameloblastoma. ABC involves ramus and molar region of mandible more than the maxilla, is symptomatic, seen in younger age group and radiographically appears unilocular with thinning, wherein OKC is asymptomatic seen in mandible 3rd molar region and epicentre is superior to alveolar canal, presents as multilocular radiolucency. Unicystic ameloblastoma is asymptomatic, occurs in mandibular third molar region and radiographically appears unilocular. Usually CGCG is unifocal in appearance, multifocal lesions should alert the clinician to the possibility of hyperparathyroidism. If bilateral then Cherubism and Noonan’s syndrome should be considered.

Although CGCG are considered as benign osseous lesions, some authors divide CGCG into 2 categories based on its clinical and radiographic features.

1. Non-aggressive: Lesions are usually slow growing, asymptomatic and do not show cortical perforation/root resorption with less chances of recurrence.
2. Aggressive: Are usually seen in young patients, are painful, grow rapidly, larger overall, often cause cortical perforation, root resorption and tendency to reoccur. As all the cases showed an acute onset, pain,rapid in growth, overall larger and radiologically showed tooth displacement,cortical expansion and perforation and involvement of the maxillary antrum. One case also showed recurrence suggestive of its aggressive nature. Hence,it can be concluded that the present cases are aggressive form of CGCG. CGCG presents with 2 major histological features, firstly, a highly cellular fibroblastic stroma with plump spindle-shaped cells with high mitotic rate. Secondly, the prominent multinucleated giant cells throughout the fibroblastic stroma, distributed irregularly often located most numerously around areas of haemorrhage. The number of nuclei ranges from only a few to several dozen.

Both aggressive and non-aggressive type of lesions appear same histologically, many authors have considered biomarkers as a means of differentiating these lesions. (9) Clinical and radiographic findings dictate the management of CGCG. Well defined localised regions are treated with curettage and show a low rate of recurrence where as for extensive multiple lesions,a more radical excision is necessary.

Many treatment modalities such as simple curettage, curettage with peripheral ostectomy, enucleation and en bloc resetion have been done, as well as alternative medical treatments. First described in 1988, the protocol suggested is the 50/50 mixture of 2 percent lidocaine with 1:1,00,000 epinephrine with triamcinolone hexacetonide 20mg/ml and to inject 2 ml/1cm of lesion as seen on a Panorex X-ray and to repeat this six times at weekly intervals, works more successfully in unilocular lesions than multilocular lesions. Calcitonin injections with varied results have been reported wherein subcutaneous injections of 100 units of calcitonin daily has been done. These injections are available as human and salmon calcitonin. Calcitonin is also available as a nasal spray (200 IU/ day) controls the osteoclasto genesis and interferon alpha injection (3x10 6 IU/day) used as adjunct to surgery, acts as antiangiogenic and inhibits bone resorption.

Conclusion

In literature, case reports mention the non-aggressive form of CGCG, the present case series have shown massive lesions with varied location and are aggressive in nature. Despite the chacteristic histologic and immunohistochemical features,CGCG remains a diagnostic challenge to both clinicians and radiologists. There are no studies larger than individual case reports to explain the radiographic features of CGCG. Thus, we would emphasise the need the need of advanced imaging modalities such as CT,CBCT to facilitate the diagnosis in cases of aggressive forms of CGCG.