PÁGINA DEL RESIDENTE

The case is presented of a 63- year-old male patient with no known drug allergies, a personal history of arterial hypertension as a result of a renal transplant, ischemic cardiopathy, neuro-sensorial deafness, and gingival hypertrophy due to immunosuppressive medication.

He presented with a gingival lesion in the right side of the maxilla that had been growing rapidly over the previous months. He commented that he had had a similar lesion some years previously that had been treated surgically in another hospital.

On examination he was found to have a lesion that measured 3 x 2 cm in diameter that was bulging through the vestibular gingiva on the upper right side. It was soft in consistency and it had poorly defined margins (Fig. 1). An OPG was requested that showed a lesion encompassing tooth Nº 13 which in turn had a possible periapical cyst.

Peripheral granuloma of giant cells

M.L. Maniegas Lozano¹, J. Giner Díaz¹, V. Ordoñez Soblechero¹, S. González Luque¹, J.M. García Rielo¹, R. Martín-Granizo²

1 Médico residente
2 Médico adjunto
Servicio de Cirugía Oral y Maxilofacial. (Jefe de Servicio: Dr. A Berguer)
Hospital Clínico San Carlos, Madrid, España

Correspondence

As there was a suspicion that this was a more aggressive recurrence of the previous lesion, a second surgical intervention was decided on. Under general anesthesia and with nasotracheal intubation, the lesion was resected with safety margins. Tooth Nº 13 was included and curettage of the bed was carried out. For closing the defect a pedicled flap was harvested of Bichat’s fat pad (Figs. 2, 3 and 4). The postoperative period was favorable and complication-free. The patient was followed at two weeks and at 3, 6 and 12 months. He was always asymptomatic and free of recurrence (Fig. 5).

The anatomopathological study revealed an ulcerated oral mucosa and underlying bone with a proliferation of multi-nucleated giant cells and atypical histiocytes and the presence of two mitoses per field at x 400 magnifications. Among the bone trabeculae there were proliferative spindle cells. The ulcerated area had necrotic detritus and suppuration. The ulcer base was made up of multi-nucleated proliferative cells (Figs. 6, 7 and 8). The lesion was finally diagnosed as peripheral granuloma of giant cells.

Discussion

Giant cell lesions constitute a group of pathological processes that is very wide and diverse from the biological as well as morphological point of view. Histologically they can resemble each other as a result of the presence of giant cells. When trying to choose suitable treatment in order to obtain a favorable prognosis, the key for their correct classification and diagnosis lies in their clinical behavior and in their radiological and histological features. From a pathological point of view they can be divided into three large groups:¹

1. Reactive Lesions. Brown tumor of hyperparathyroidism, hemophilic pseudotumor and intraosseous hemorrhage.

2. Benign lesions. Giant cell granuloma or reparative granuloma, non-ossifying fibroma, giant cell tumor, aneurysmal bone cyst, chondroblastoma, chondromyxoid fibroma, Langerhans cell histiocytosis, pigmented villonodular synovitis.

3. Malignant lesions: Osteosarcoma, malignant fibrous histiocytoma, clear cell chondrosarcoma, metastatic carcinoma.

Giant cell granuloma was first described by Jaffe² in 1953 as a lesional reaction with a reparative purpose. However, later studies have since shown that the reparative characteristics are minimal. It is a benign lesion that constitutes 7% of all benign tumors that appear in the mandible.³ It has been defined by the WHO as an intraosseous lesion consisting of cellular fibrous tissue that contains multiple hemorrhagic foci and multinucleated giant cell aggregates and occasionally bony trabeculae. ⁴

It is found more frequently in the mandible than in the maxilla (2:1) although it can also appear in the orbit, paranasal bones, cranium and the small bones of the hands and feet. It has a predilection for the anterior region of the mandible, although it can also appear from premolars to molars. However, in the maxilla, finding it distally to the canines is unusual. It manifests more frequently in females (2:1) and during the first three decades in life, and it affects mainly children and young adults.^5,6 Its origin is unknown, although it is thought to have a genetic determinant and to be related to previous trauma and/or inflammation.

Most patients are asymptomatic, although there may be swelling around the face or in the oral cavity. There may be an onset of pain, tooth mobility, facial asymmetry and, more unusually paresthesias. This is as a result of the lesion not invading the perineural sheath, despite showing an expansive growth pattern.^7,8 The slower growing lesions are asymptomatic and they tend to be diagnosed by chance in routine radiographies. Those with more aggressive growth are painful, and there is facial swelling and obvious tissue destruction. They are more likely to recur and their treatment is more contested.⁷

Radiological diagnosis can vary substantially from welldefined unilocular lesions to multilocular areas with a soap bubble pattern, cortical thinning, irregular borders or rhizolysis.⁶ The layer of bone around the lesion tends to be thin and there may or may not be bone destruction. It is common to find bone lysis in the orthopantomography, although there may be areas of "hour glass" radio-condensation in the maxilla.⁵ The unspecific signs in the radiological pattern found in the OPG as well as in the CT scan result in giant cell granuloma being indistinguishable from other radiolucid bone lesions such as the odontogenic cyst, aneurysmal bone cyst, ameloblastoma, odontogenic myxoma and odontogenic fibroma.⁹ The lesion is highlighted in MR images when iodinated contrast material or intravenous gadolinium is used. A low signal will appear on T1 weighted sequences, which will be more intense on T2. Fibrous hypointense walls have also been described. Cystic areas are uncommon and they make up just a small percentage of the lesion when they do appear. Calcification areas can also be appreciated in the interior.⁹

Histologically a fibrocellular stroma can be observed with giant multinucleated cells (5- 10 nuclei per cell), fibroblasts and spindle cells surrounded by hemorrhagic foci. The formation of reactive bone and a large amount osteoblastic activity is typical. Atypia tends not to be observed. Spindle cells tend to have osteoclastic activity.

The differential diagnosis should be carried out with the following entities: aneurysmal bone cyst, cherubism (bilateral multifocal lesions are typical in the mandible),⁵ brown tumor of hyperparathyroidism (an increase of serum calcium, alkaline phosphate and parathyroid hormone and a reduction of serum phosphate),⁹ ameloblastoma, fibrous dysplasia and giant cell tumor (located chiefly in the epiphysis of long bones, the cranium, facial bones and paranasal sinuses, it appears around the 40 to 50 age mark. The histological section will show many more nuclei in giant cells and a more regular distribution through out the tumor).¹

Treatment for giant cell granuloma is initially surgical, although there are currently other therapeutic options that are equally recommendable. Surgery consists in carrying out a resection of the lesion and exhaustive curettage of the dental roots and the remaining bony walls. The teeth enveloped by the lesion should have root canal treatment prior to the surgery in order to guarantee their preservation. This treatment has achieved high cure rates with few cases of recurrence. ^8,10 Despite this, a small percentage of these lesions are aggressive and they will destroy or perforate cortical bone resulting in the need for more aggressive treatment such as local excision and wide resection margins. Teeth may be lost and there may be defects in tissue continuity making aesthetic and functional reconstruction necessary. As a result of this, non-surgical therapeutic alternatives have arisen over the last few years that have had good results with regard to aggressive lesions.^5,12-18

• Intralesional corticoids: The possibility of using these arises as a result of the microscopic similarity observed in sarcoidosis and in giant cell lesions. The action mechanism is based on the inhibition of osteoclastic activity leading to faster bone regeneration to include the contours that have been lost. The treatment protocol consists of 6 weekly injections.¹¹ Some studies have demonstrated good results despite being contraindicated in certain medical situations (DM, peptic ulcer, immunodepressive conditions, etc.).^12,13

• Subcutaneous calcitonin: This was first described in 1993 and numerous references have since appeared in the literature with regard to its use when treating giant cell granuloma.¹² It has an action mechanism that is similar to that of the brown tumor of hyperparathyroidism, based on the presence of calcitonin receptors in lesions with giant cells that inhibit osteoclastic bone resorption and that act on a type of cell that is present in the lesion. The hormone responsible, should it exist, has yet to be identified.^11,14 After a year of treatment with calcitonin, complete remission of the lesion has been observed with no apparent signs of recurrence.^15,16 Calcitonin therapy is still unpleasant and lengthy, which results in it being poorly tolerated by some patients such as children.¹⁵ In a study, Pogrel concludes that, while it is still a viable therapy for treating these lesions, given the handicap concerning treatment length, it would be appropriate to reserve it for multiple, aggressive or for recurrent lesions.¹¹

• Interferon Alpha: The action mechanism assumes the vascular nature of the lesion. Interferon suppresses angiogenesis provoking the involution of the lesion.¹⁷

The role played by these therapies should be further investigated so that satisfactory results permitting complete cures can be achieved and recurrences avoided. Finally, periodic follow-ups should be carried out over a 1-2 year period given the possibility of recurrence (11-49%), which increases in aggressive lesions causing local destruction, rapid growth, rhizolysis and paresthesias, also in young people and in lesions located in the maxilla5 as occurred in the present case report.

Correspondence:
Lourdes Maniegas
Servicio de Cirugía Oral y Maxilofacial
Hospital Clínico San Carlos
C/ Prof. Martín Lagos s/n
28040 Madrid, España
Email: lmaniegasl@yahoo.es

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