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A 29-year-old woman with no known allergies to any medicine and with a background of tonsillectomy, adenoidectomy and hepatitis A, attended our unit following referral by her dentist as she had what appeared to be cyst on her left mandible that had been developing for a year and a half. The patient complained of discomfort in this area but the oral aperture was not affected nor was there any paresthesia of the lower lip.

During the physical examination, a tumor on the left half of the mandible was observed that measured 4 x 3 cm. It was painless, with a hard consistency and it was causing a bulge of the external mandibular cortical layer. None of her teeth were giving her any pain nor did they show any pathological movement.

In the orthopantomography a unilocular image could be identified that was radiolucent and osteolytic. It had welldefined borders with small radiopaque areas in its interior. It was by the third mandibular section and it was affecting 4.1, 4.2 and from 3.1 to 3.5. This image appeared to partly encompass the dental canal (Fig. 1).

With the presumed diagnosis of radicular cyst of the mandible, the affected teeth received endodontic therapy before the definitive surgical treatment.

Giant cell tumor of the mandible
Tumor de células gigantes mandibular

G. Gómez Oliveira¹, A. García-Rozado González², J.L. López-Cedrún³

1 Médico Residente
2 Médico Adjunto
3 Jefe de Servicio
Servicio de Cirugía Oral y Maxilofacial
Complejo Hospitalario Juan Canalejo. La Coruña, España.

Correspondencia:
C/ Almirante Mourelle 29 2º
15011 La Coruña, España.
e-mail: guis@canalejo.org

The patient was operated on under general anesthesia in order to remove the lesion. An intraoral approach was made by means of a full-thickness gingival flap. The intraoperative image of the lesion did not correspond with the radiologic image previously obtained, as this appeared to be a solid tumor and it was causing the vestibular cortex to bulge together with erosion of the lingual surfaces. Given the diagnosis of ameloblastoma or mandibular myxoma, it was decided that the lesion should be resected and that the remaining cavity be trimmed back with a bur. Finally, an apicectomy was carried out of teeth 4.2, 4.1 and from 3.1 to 3.5.

The histological study of the sample showed the presence of multiple fragments of tissue with irregular shapes and with different characteristics. Some of these had a bonelike consistency while others were similar to cartilage. The microscopic analysis revealed a tumor-like proliferation of giant multinucleated cells that were evenly rounded, some of them with a prominent nucleolus tending to group together in clusters of small nests. At the same time tumor stroma was observed that was made up of a smaller cellular colony that had fusiform nuclei. Similarly, newly formed as well as degenerated bone trabeculae could be identified with osteoblastic-osteoclastic rimming. In areas further away there was a trabecular component with mature bone and basophilic degeneration (Fig. 2).

Following the surgical intervention the patient complained of hypoesthesia of the left dental nerve.

Six months after surgery the radiographic tests confirmed progressive bone fill of the lesion (Fig. 3). The hypoesthesia of the lower lip disappeared completely.

Discussion

Giant cell tumor is defined as a primary benign neoplasm of the bone that is locally aggressive.^1,3-6 It was first described by Sir Astley Cooper en 1818.⁶ It represents 5–15% of all benign bone tumors.^1,4,6 It more commonly affects women between the 2^nd and 3^rd decades in life.^2,4,5-8,13 Between 1 and 3% occur in children under the age of 14.⁶ It has a high prevalence in China and in Southern India (Andhra Pradesh State).⁶ It tends to be located in the epiphyses and metaphyses of long bones (knee, femur, tibia, radius).^4,7,8 In the maxillofacial area they are very uncommon and they arise, in order of frequency, in the mandible, upper maxilla, skull base and mandibular condyle.^1-4,8-10,13 Ruling out an association with Paget’s disease is essential in these cases.^6,8 It represents the most common lesion associated with secondary aneurismatic bone cysts (39%).⁶

There are various theories as to its etiopathogeny: inflammatory, angiogenic and osteoclastic, although none of these have been clearly demonstrated. Recently the role played by the suppressor gene p53 in its genesis has been confirmed.³

It usually appears as a solitary tumor, that is asymptomatic or painful, that expands rapidly tending to arise in the vestibular fold.^2,6,7,13 It can cause loss of teeth or shifting, limited oral aperture, pathological fractures (11-37%) or paresthesias.⁶ On other occasions it appears as an incidental radiolucency during conventional radiologic examinations.^2,6

Unusual multicentric shapes may appear (<1%), but these tend to be associated with Paget’s disease,³ affecting younger age groups and their behavior is much more aggressive. ^4,6

Radiologically a multilocular radiolucent "soap-bubble- like" image will appear that is similar to that of the ameloblastoma. More unusually a unilocular image will appear. Sometimes cortical expansion and thinning appears together with a sclerotic rim and root resorption. In half of the cases there is destruction of the bone cortex.^1,2,4,6,13

CAT scans and NMR enable a better definition of the real extension of the tumor and they help differentiate it from other bone lesions.^1,3,6 Angiographic studies are of great assistance as in most cases a hypervascular lesion is shown (60-65%), although there are hypovascular cases (26-30%) or even avascular cases (10%).⁶

It is a neoplasm with malignant potential, especially when affecting elderly males.⁶ The primary form is rare,³ occurring as a result of sarcomatous degeneration secondary to radiotherapy (5-10% of cases).^1,6 Less frequently they will appear following long latency periods or following repeated surgical resection.⁶ Metastases is unusual, tending to consolidate in the lungs. (1-10 %).^4,5,7

Campanacci (1987)¹¹ divided the tumors into 3 stages: Stage I: the lesion is intraosseous and inactive histologically and radiologically; Stage II: the lesion is intraosseous and there is expansion and cortical thinning, but the periosteum remains intact and it is histologically benign; Stage III: the lesion is aggressive and extraosseous but with benign histology. ^4,6 The large majority (70-80%) correspond to stage II.⁶

Other authors classify them as either aggressive or nonaggressive. The most common aggressive form consists of large, rapidly growing, painful tumors that produce bleeding and tooth movement. There can be root resorption and perforation of the bone cortex. The recurrence rate is high, especially during the first 3-4 years following treatment and if simple curettage has been carried out (40-60%),^1,4,6-8 while en bloc resection reduces this to 7-10%.^6,7

The non-aggressive form corresponds to asymptomatic tumors that are smaller, there being much lower recurrence rate following treatment.^1,2,5

The diagnosis is complicated and it should be based on clinical, radiological and histological findings in unison. It is often necessary to study calcium, phosphate and serum PTH in order to differentiate them from the brown tumor in hyperparathyroidism.^4,6,8

The tissue of the tumor is friable and highly vascular,¹³ with small cystic areas, grayish white necrotic foci, hemorrhages, fibrosis and xanthomatous areas.⁶

The characteristic cell is giant and multinucleated. It is thought to represent a neoplastic osteoclast.^3,4,6 It is positioned on a stroma of mesenchymal spindle-shaped cells that are fusiform and highly vascular, that contain capillary veins with fine walls and small hemorrhagic areas.⁶ There are areas of ossification as well as small trabeculae of residual lamellar bone and hemosiderin deposits. FNA studies have demonstrated the existence of calcitonin receptors in the cytoplasm of giant multinucleated cells.⁴

The differential diagnosis should be established including benign giant cell entities such as aneurismal bone cysts, central giant cell reparative granulomas, cherubism and brown tumors of hyperparathyroidism with similar radiological entities such as the odontogenic myxoma, osteoblastoma, chondroblastoma and the ameloblastoma.⁸ Other lesions that should be taken into account are foreign body reactions, vascular lesions and malignant lesions, especially the osteosarcoma and the much less common histiocytoma of Langerhan’s cells and leukemia.^1,2,4,6,7

The only prognostic factors that have been described are the histological type and degree of expression of the suppressor gene p53, which is related to the probability of developing lung metastasis and local recurrence.³

The treatment of choice is surgical, and en bloc resection is recommended with wide security margins, given the high degree of recurrence and the potential shown for malignant transformation.^3,4 In cases where a histological diagnosis is carried out following surgical excision with free margins, a following involving periodic check-ups is recommended. ⁴

In the case of larger sized lesions or those that are more aggressive, coadjuvant therapy can be used in order to reduce the size and risk of tumor bleeding during surgery. Of these presurgical embolization stands out,⁶ together with intralesional injection of corticoids,^2,3,5,12 and the systemic administration of calcitonine.³ It should be pointed out that with a daily subcutaneous injection of interferon alpha 2a, complete tumor regression has been achieved, as well as bone filling in the residual cavities.^2,5,6

Radiotherapy on its own is not recommended due to the possibility of malignization, unless patients have rejected surgery, although some authors have reported that it has been used successfully in primary tumors as well as in recurrences. ^3,4,6

Conclusions

Giant cell tumor is a benign primary bone neoplasm that behaves aggressively. Its appearance radiologically and histologically can be confused with other entities that are benign as well as malignant and it has to be differentiated from these. The diagnosis is based on radiologic and histologic examination as well as on clinical and serologic tests. The recommended treatment is en bloc surgical resection in order to avoid its frequent recurrences, except when the diagnosis has been reached following surgical excision.

References

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