Peripheral giant cell granuloma. 
A report of five cases and review of the literature

CHAPARRO-AVENDAÑO AV, BERINI-AYTÉS L, GAY ESCODA C. PERIPHERAL GIANT CELL GRANULOMA. A REPORT OF FIVE CASES AND REVIEW OF THE LITERATURE. MED ORAL PATOL ORAL CIR BUCAL 2005;10:48-57.

 

ABSTRACT

Peripheral giant cell granuloma (PGCG) is a relatively frequent benign reactive lesion of the oral cavity, originating from the periosteum or periodontal membrane following local irritation or chronic trauma. PGCG manifests as a red-purple nodule located in the region of the gums or edentulous alveolar margins, fundamentally in the lower jaw.
The lesion can develop at any age, though it is more common between the fifth and sixth decades of life, and shows a slight female predilection. PGCG is a soft tissue lesion that very rarely affects the underlying bone, though the latter may suffer superficial erosion.
The present study reviews 5 cases of PGCG, involving 3 males and 2 females between 19-66 years of age, and with presentation in the upper jaw in three cases. Two patients showed radiological concave depression images corresponding to bone resorption.
Treatment consisted of resection and biopsy, using a carbon dioxide laser in 2 cases and a cold scalpel in the remaining 3. There were no relapses during postoperative follow-up (range 10 months to 4 years). The differential diagnosis of PGCG includes lesions with very similar clinical and histological characteristics, such as central giant cell granuloma, which are located within the jaw itself and exhibit a more aggressive behavior. Only radiological evaluation can establish a distinction.
The early and precise diagnosis of these lesions allows conservative management without risk to the adjacent teeth or bone.

Key words: Peripheral giant cell granuloma, giant cells epulis, giant cells hyperplasia.

 

INTRODUCTION

Peripheral giant cell granuloma (PGCG) is the most frequent giant cell lesion of the jaws, and originates from the connective tissue of the periosteum or from the periodontal membrane (1-3), in response to local irritation or chronic trauma (4,5).

The condition has also been referred to as peripheral giant cell tumor, giant cell epulis, osteoclastoma, reparatory giant cell granuloma, and giant cell hyperplasia of the oral mucosa (6).

Clinically, PGCG manifests as a firm, soft, bright nodule or as a sessile or pediculate mass. The color can range from dark red to purple or blue, and the surface is occasionally ulcerated (1-3,5,7). The lesions range in size from small papules to enlarged masses, though they are generally under 2 cm in diameter, and are located in the interdental papilla, edentulous alveolar margin, or at marginal gum level (1,6,7).

Although incipient lesions may bleed and induce minor changes in gingival contour, gradual growth in some cases produces an important tumor mass that adversely affects normal oral function.

Pain is not a common characteristic, and lesion growth in most cases is induced by repeated trauma (4). These are soft tissue lesions that rarely affect the underlying bone, though the latter may suffer erosion (1-3).

Treatment comprises surgical resection, with extensive clearing of the base of the lesion to avoid relapses (6).

The present study describes 5 cases of peripheral giant cell granuloma and offers a review of the literature to define the clinical, radiological and histological characteristics of PGCG. Finally, the importance of these lesions in the differential diagnosis of gingival lesions is emphasized.

CLINICAL CASES

Case 1
A 63-year-old male with diabetes subjected to insulin treatment (Insulatard NPH®) for the previous year presented a history of cerebrovascular stroke with involvement of the right side of the body 10 years before. He was receiving antiplatelet treatment, with Triflusal 300 mg (1-0-1) and Nimodipine 30 mg (1-1-1). The patient had undergone surgery for benign prostate hyperplasia 5 years before. There were no known drug allergies, and the patient smoked one packet of cigarettes a day.

The patient was referred to our Service for resection-biopsy of a gingival tumor that had appeared one year before and was located between the upper central and left lateral incisors. The patient reported no pain, though the lesion tended to bleed when eating, and had grown in size in the last few months.

Clinical exploration revealed a nodular, pediculate gingival tumor located in the interincisal papilla of 2.1 and 2.2, and extending palatal. The lesion was purple in color, measured 1.2 x 1.6 cm in size, and had an ulcerated surface (figure 1).

The patient was partially edentulous, with deficient oral hygiene, advanced adult periodontitis, and grade II mobility of 2.2.

The periapical X-rays showed vertical alveolar crest loss between 2.1 and 2.2, with bone resorption to the middle third of the roots.

Treatment consisted of resection-biopsy of the lesion under infiltrating local anesthesia and using a cold scalpel.

The histological study confirmed the diagnosis of peripheral giant cell granuloma (figure 2).

The postoperative course was uneventful, with persistence of grade II mobility of 2.2. Control examination after 6 months showed grade I mobility of 2.2. One year after resection there are no signs of relapse.

Case 2
A 19-year-old male without disease antecedents of interest or known drug allergies was referred to our Service with a tumor lesion for the previous 6 months, located in an edentulous zone corresponding to the lower right second premolar. The patient referred no pain, though the lesion tended to bleed slightly with tooth brushing or chewing.

Inspection revealed an exophytic, blue-colored lesion with a large base, in the edentulous margin of 4.5. The tumor measured 1.8 x 1 cm in size, and was of a soft consistency.

The X-ray study showed slight bone resorption in the form of a concave depression, with a normal trabecular component.

The lesion was removed under infiltrating local anesthesia and using a cold scalpel. The histological report of the resection piece confirmed the diagnosis of peripheral giant cell granuloma. There were no complications in the immediate postoperative period. At the successive controls, and after 10 months, there is no evidence of relapse.

Case 3
A 66-year-old woman without disease antecedents of interest or known drug allergies was sent to our Service for removal of a two-month-old lesion located in the edentulous region of the right lower first premolar. She reported no pain, though the tumor bled while eating.

Intraoral examination revealed an exophytic lesion with a pediculate base, measuring 1.5 x 1.2 cm in size, of a soft consistency and purple in color (figure 3).

The patient showed partial lower jaw edentulism, and wore removable partial dentures. She suffered moderate periodontitis affecting the lower incisors. The X-ray study showed no signs of bone involvement.

Resection-biopsy was performed under infiltrating local anesthesia and using a carbon dioxide laser (5 W). The histological study showed the presence of peripheral giant cell granuloma. There were no complications in the immediate postoperative period, and no relapse has been observed during the subsequent two-year follow-up period.

Case 4
A 64-year-old male with a history of cardiac arrhythmia (atrial fibrillation, paroxysmal supraventricular tachycardia) and alcoholic live disease diagnosed at age 48 was receiving medication in the form of Atenolol 100 mg (1-0-1) and Diazepam 5 mg (0-0-1). He had been subjected to surgery at 50 years of age due to a perianal fistula. There were no known drug allergies.

The patient was sent to our Service for the removal of an exophytic lesions identified two months previously and located in the region of the hard palate, at upper right second molar level. The lesion caused pain in response to palpation.

The intraoral examination identified a pediculate indurated nodular lesion measuring 0.5 cm in diameter and of a pink color.

The patient was partially edentulous, with missing 1.6 and deficient oral hygiene. The periapical X-ray study showed no signs of bone involvement.

The lesion was removed under infiltrating local anesthesia and using a cold scalpel. The histological diagnosis was peripheral giant cell granuloma.

The postoperative control after 7 days showed very slow wound healing, but no associated symptoms. One month after resection, the wound presented an eroded appearance but no tumor mass was palpable. The wound subsequently healed completely and without sequelae two months after surgery.

There were no posterior signs of relapse during the four-year follow-up period.

Case 5
A 49-year-old woman without disease antecedents of interest or known drug allergies was referred to our Service with a tumor lesion for the previous year located in the edentulous alveolar margin corresponding to the zone of the upper right first premolar, palatal and distal to 1.3. She referred only slight discomfort on fitting her upper partial dentures.

Exploration revealed a soft, large-base exophytic purple-colored lesion measuring 1.4 x 0.7 cm in size.

The patient was partially edentulous and wore removable partial dentures. Oral hygiene was very deficient. The lesion zone coincided with a denture retainer. Tooth 1.3 was vital, non-painful to percussion, and showed no mobility.

The X-ray study showed bone resorption in the form of a concave depression in the edentulous region of 1.4.

The lesion was subjected to resection-biopsy under infiltrating local anesthesia, and using a carbon dioxide laser (5 W). The histological diagnosis was peripheral giant cell granuloma.

There were no postoperative complications or signs of relapse after three years of follow-up.

DISCUSSION

Peripheral giant cell granuloma (PGCG) is not a true neoplasm but rather a benign hyperplastic reactive lesion caused by local irritation or chronic trauma. PGCG originates from the periodontal ligament or mucoperiosteum (1-3). Although the etiology is subject to controversy, many authors consider the origin to comprise an abnormal proliferative response to aggression (6,7). Different local causal factors have been associated to PGCG, including complicated dental extractions, dental restorations in poor conditions, food impaction (dental malpositioning), plaque and tartar, etc. (2,3,8-11).

The lesions can appear at an age, though the highest incidence (40%) is in the fourth to sixth decades of life (5,6,19). In 20-30% of cases they manifest in the first and second decades (2,12,13). Reichart and Philipsen (14) consider the peak incidence to be between 20-60 years of age, with an average of 30 years according to Shafer and Levy (4) and Giansanti and Waldron (12). Andersen et al. (9), in a series of 97 cases of PGCG, reported a marked prevalence between 5 and 15 years of age. In our series, the age of the patients was in the 19-66 years interval, with an average at initial manifestation of 52 years, and an increased incidence in the sixth decade of life (Table 1).

PGCG affects females more often than males (1,2,7,15), with a proportion of 1:1.5 or 1:2 according to Reichart and Philipsen (14) or Giansanti and Waldron (12), respectively. However, Bhaskar et al. (8) in a review of 50 cases, reported a slight predilection for the male sex. Three of our 5 patients were men (Table 1).

PGCG is more common in the lower jaw (55%) than in the upper jaw (7,12) - the reported proportion being 2.4:1 (14). Gándara et al. (15), in a series of 13 cases of PGCG, found 8 lesions to be located in the upper jaw. In our own series, three lesions were found in the upper jaw – though this distribution may be attributed to the few cases involved (Table 1).

The lesions generally develop in the gingival tissue or alveolar processes (1,3,14) of the incisor and canine region (4,12), though according to Pindborg (16) the preferential location is the premolar and molar zone. Of our 5 cases, three were located in the edentulous alveolar margins of the premolar region, with one case palatal to the molars and another in the attached gums between upper incisors and extending palatal (Table 1).

Lesion size varies from 0.5 to 1.5 cm in diameter (1,3), though there have been reports of masses in excess of 5 cm, where factors such as deficient oral hygiene or xerostomia appear to play an important role in lesion growth (7). None of our cases exceeded 2 cm in size (Table 1).

The X-ray features are nonspecific, with foci of bone metaplasia in some cases (6). Some patients may present evidence of bone involvement beneath the lesion (1,17), in the form of superficial alveolar bone resorption – observable on periapical X-rays (4,5,18). Widening of the periodontal ligament space is often a finding (17,19-21) associated to dental mobility (4,5,18), though in some situations it may represent lesion spread around the root (4). Detailed examination of the zone can reveal small bone spicules extending vertically towards the base of the lesion. In edentulous areas the cortical bone exhibits a concave resorption zone beneath the lesion, - a feature that may be referred to as a “leveling” effect (1,17). When the tumor is located in dentate areas, the X-ray study may show superficial destruction of the alveolar crest or margin at interdental bone level (1,22).

X-rays are important for determining whether the lesion is of gingival (i.e., peripheral) origin or of bone (central) origin with spread towards the surface (17). In our series of PGCG, two patients showed radiological evidence of bone resorption in the form of a “leveling” image (Table 2).

Case 5 presented such a “leveling” image corresponding to bone resorption – the differential diagnosis being established with central giant cell granuloma. The common X-ray presentation of this latter type of lesion is an ovoid or rounded and well defined radiotransparent image which may be uni- or multilocular. Case 2 in urn showed slight concave resorption, with a normal bone trabecular component. Case 1 was located between two upper incisors. and the lesion induced alveolar crest resorption. Clinically, this patient presented grade II mobility of the lateral incisor that decreased after removal of the tumor. Nevertheless, such mobility could also be attributed to the advanced periodontal disease identified in this patient.

Cases of PGCG have been documented in children, where the lesion appears to be more aggressive, with absorption of the interproximal crest area, displacement of the adjacent teeth (4,5,18,23), and multiple recurrences (23).

A range of disorders should be considered in the differential diagnosis of peripheral granuloma, including pyogenic granuloma, fibrous epulis, peripheral ossifying fibroma, inflammatory fibrous hyperplasia, peripheral odontogenic fibroma, hemangioma cavernosum and papilloma. The histological study of the resected tissue establishes the definitive diagnosis.

From the histopathological perspective, the principal differential diagnosis is established with central giant cell granuloma, though the clinical and radiological findings offer a clear and conclusive distinction between central and peripheral giant cell granuloma. The X-ray features are very important for determining whether the lesion is of gingival origin or arises centrally with spread towards the surface. In the case of central lesions it is essential to discard other possibilities such as giant cell tumors, ameloblastoma and aneurysmal bone cysts, before establishing the definitive diagnosis (24).

Histologically, PGCG is described as a non-encapsulated mass of tissue composed of a reticular and fibrillar connective tissue stroma containing abundant young connective tissue cells of ovoid or fusiform shape, and multinucleated giant cells (1). In some cases the giant cells are reminiscent of osteoclasts (17), while in other cases they are considerably larger than typical osteoclasts – though only rarely do these cells have normal bone resorptive functions (1).

The lesions typically contains abundant capillaries, particularly in the more peripheral zones, and giant cells are sometimes identified in the internal wall of these vessels. Hemorrhagic foci are also typical, with the release of hemosiderin pigment and posterior invasion by mononuclear phagocytes and inflammatory cells (1). The giant cells are immersed within the stromal component of fibroblasts, immature cells and ground substance (collagen fibers, reticulin and ground substance proper) – the composition of which varies according to the evolutive stage of the lesion (6).

The histological study centers on three points: epithelium, connective tissue zone and medullary or core region:

- The lining epithelium corresponds to the squamous structure of the gums, which may suffer ulcerative changes.
- The subepithelial connective tissue zone is composed of connective tissue with abundant small-caliber blood vessels. An acute inflammatory infiltrate is often seen.
- The medullary or core region is where the giant cells are located. These may be of two types (11):

Type A cells: polynuclear eosinophilic cells with a diffuse and abundant cytoplasm. The nucleus is prominent, and the chromatin is distributed along the internal membrane.
Type B cells: cells with a regular and well defined, more chromatic and larger cytoplasm. The nuclei present poorly defined limits and show a central accumulation tendency, with intense hyperchromatism.

The origin of the giant cells has not been established, though some investigators suggest that they arise from the endothelial cells of the capillaries (1). Two theories have been proposed to explain the origin of these cells: a traumatic mechanism on one hand and a proliferative origin on the other, in which the lesion does not arise a consequence of prior trauma but secondary to alterations of the vascular endothelium (25,26).

Ultrastructural and immune studies have shown the giant cells to derive from macrophages, though these cells are not functional in terms of phagocytosis and bone resorption (24).

Souza et al. (27) conducted immunohistochemical studies to show the existence of increased proliferative activity and greater growth of peripheral lesions compared with central giant cell granulomas.

On the other hand, Gunhan et al. (28), in their study of 26 cases of PGCG, considered that these lesions could be influenced by sex hormones. These authors found the giant cells to be a potential target for estrogen (but not progesterone) action.

In rare cases, giant cell granulomas are an oral manifestation of hyperparathyroidism (4,19,29). The latter can be suspected when multiple lesions are identified and the patient suffers recurrences despite adequate treatment (4,5). The lesions typically associated with hyperparathyroidism appear centrally in bone (30) and are referred to as brown tumors (30). In the lower jaw, these intrabony lesions can perforate the cortical layer, spreading towards the soft tissues and imitating a peripheral lesion (30).

A parathyroid tumor or chronic renal failure primarily or secondarily can give rise to increased parathyroid hormone (PTH) production, which in turn favors the formation of giant cell lesions. Children with hypophosphatemic rickets – a condition associated to subclinical hyperparathyroidism – are also at an increased risk of developing such lesions (12). Histologically, brown tumors cannot be distinguished from giant cell granulomas (31).

Giansanti and Waldron (12), in a review of 720 cases of peripheral giant cell granuloma, observed no relation to hyperparathyroidism. In general, fewer than 10% of cases of hyperparathyroidism are associated to peripheral or central giant cell lesions (30).

The treatment of PGCG comprises surgical resection and suppression of the underlying etiologic factors (1,5) – with elimination of the entire base of the lesion. If resection is only superficial, the growth may recur (1). Most lesions respond satisfactorily to thorough surgical resection, with exposure of all the bone walls. When the periodontal membrane is affected, extraction of the adjacent teeth may prove necessary to ensure full resection (17), though this is initially contraindicated (1).

Recurrence is infrequent and is observed in 5% and 11% of cases according to Eversole (11) and Mighell et al. (13), respectively. In our series, resection was carried out in three cases with a cold scalpel, while a carbon dioxide laser was used in the remaining two cases – no differences in postoperative course being observed according to the type of technique used. None of our patients showed relapse after a follow-up period of between 10 months and 4 years (Table 2).

The literature reports no differences between cold scalpel or carbon dioxide laser resection of PGCG. The advantages of laser resection are that it causes less intraoperative bleeding, sterilizes the wound, requires no suturing and affords improved postoperative patient comfort (32). In contraposition, the carbon dioxide laser is of limited applicability in lesions with adjacent bone involvement, where careful surgical curettage is required. Laser resection is not indicated in such cases.

In conclusion, the early and precise diagnosis of PGCG, based on the clinical and radiological findings and histological study, allows conservative management with a lesser risk for the teeth and adjacent bone.

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