Immunocytochemical Study of Giant Cell Fibroma
 
 

Erica CAMPOS
Ricardo Santiago GOMEZ

Departamento de Cirurgia Buccal e Patologia, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Belo Horzonte, MG, Brasil


Braz Dent J (1999) 10(2): 89-92  ISSN 0103-6440

| Introduction | Material and Methods | Results | Discussion | Conclusion | Acknowledgments | References|


Giant cell fibroma (GCF) is a non-neoplastic lesion of the oral mucosa. The origin of stellate and multinucleate cells of GCF is not well known. The purpose of the present article was to investigate the immunoreactivity of these cells for leukocyte common antigen, vimentin, tryptase, HLA-DR, alpha-smooth muscle actin, CD68, and S-100. The results showed positive staining only for vimentin. This suggests that the stellate and multinucleate cells of GCF have a fibroblast phenotype.


Key Words: fibroma, immunohistochemistry, oral mucosa.


Introduction

Giant cell fibroma (GCF) is a benign non-neoplastic lesion first described by Weathers and Callihan (1974). It occurs in the first three decades of life and predominates in females (Houston, 1982; Bakos, 1992). Clinically, the GCF presents as an asymptomatic, papillary and pedunculated lesion. The most predominant location is the mandibular gingiva (Houston, 1982; Bakos, 1992). Histologically, the GCF is distinctive, consisting of fibrous connective tissue without inflammation and covered with stratified squamous hyperplastic epithelium. The most characteristic histological feature is the presence of large spindle-shaped and stellate-shaped mononuclear cells and multinucleated cells. These cells occur in a variety of lesions, such as the fibrous papule of the nose, ungual fibroma, acral fibrokeratoma, acral angiofibroma and desmoplastic fibroblastoma (Swan, 1988; Pitt et al., 1993; Karabela-Bouropoulou et al., 1999; Jang et al., 1999).
Despite many studies, the nature of the stellated multinucleate and mononuclear cell is not clear (Weathers and Campbell, 1974; Regezi et al., 1987; Odell et al., 1994; Magnusson and Rasmusson, 1995). The purpose of the present study is to describe immunohistochemical findings of GCF.


Material and Methods

Biopsies from 9 cases diagnosed as GCF were retrieved from the files of the Minas Gerais Federal University Service of Oral Pathology. Clinical information of the cases selected are presented on Table 1. Formalin-fixed, paraffin-embedded tissue blocks were cut at 5 µm and stained with hematoxylin and eosin. Sections of 3 µm were subjected to the biotin-streptavidin amplified system. Since formalin fixation and paraffin-wax embedding interfere with immunocytochemical detection of some antigens, microwave stimulation (citric acid, pH 6.0) was carried out to overcome these problems as described by Shi et al. (1991) and Cattoreti et al. (1993). As this pre-treatment did not improve the quality of the reactions for the detection of the antigens alpha-smooth muscle actin and S-100 protein, it was not used in these assays. The slides for HLA-DR detection were submitted to a microwave/citrate buffer pre-treatment for 10 min, while for the other antibodies the time was of 5 min. All sections were then immersed in 3% methanol-hydrogen peroxide for 10 min to block endogenous peroxidase activity and incubated with the primary antibody for 18 h at 4oC with 1% bovine serum albumin. Table 2 summarizes the antibodies, dilution, antigen and cell specificity of the primary antiserums used in this study. After washing in Tris-HCl buffer (pH 7.4), the sections were 1) incubated at room temperature with biotinylated anti-mouse and anti-rabbit immunoglobulin (Biogenex, San Ramon, CA, USA) diluted 1:50 in Tris-HCl (pH 7.4) for 20 min; 2) washed with Tris-HCl (pH 7.4) twice for 10 min; 3) incubated for 20 min with horseradish peroxidase-conjugated streptavidin (Biogenex) diluted 1:50 in Tris-HCl (pH 7.4) for 20 min; 4) washed with Tris-HCl; 5) incubated for 3 min with 0.03% diaminobenzidine tetrahydro-chloride and 0.3% H2O2 in 5 mM Tris-HCl buffer at pH 7.4; 6) rinsed in distilled H2O for 10 min and counterstained with hematoxylin. Appropriate positive control samples of oral tissues fixed and processed in the same manner were used. Omission of the primary antibodies were performed for negative controls.


Results

The GCF samples were characterized by the presence of large stellate cells with basophilic cytoplasm with dendritic-like processes. The cells showed a single nucleus, but two and occasionally several nuclei were also seen (Figure 1). A retraction space around these cells was seen. The stroma was composed of immature cellular fibrous tissue covered by hyperplastic and papillary epithelium. Inflammatory cells infiltrate was often mild.
Immunoreactivity in the stellate and multinucleate cells was consistently positive only for vimentin (Figure 2). All specimens were negative for CD68, HLA-DR, tryptase, leukocyte common antigen (LCA), and S-100 protein.


Discussion

It has been suggested that the mononuclear and multinucleated cells of GCF might be melanocytes and Langerhans’ cells (Weathers and Callihan, 1974; Houston, 1982). However, the negative staining for S-100 excludes this hypothesis. Similar results were also reported by Odell et al. (1994) and Magnusson and Rasmusson (1995). An endothelial or myofibroblastic origin is unlikely by the negative reaction for alpha-smooth muscle actin observed in our data.
The possibility that these cells are derived from macrophage-monocyte lineage is not supported by the negative staining for CD68, LCA and HLA-DR. These results have been previously reported (Odell et al., 1994; Magnusson and Rasmusson et al., 1995). A mast cell origin is incompatible with a negative reaction for tryptase.
Our results are consistent with fibroblast origin. Magnusson and Rasmusson (1995) reported that stellate and angular cells of GCF were also only vimentin-positive. Odell et al. (1994) found that these cells were positive for prolyl-4-hydroxylase and vimentin, indicating a functional fibroblast differentiation. These authors also observed that most of these fibroblasts were negative for factor XIIIa, excluding the possibility of dendrocyte phenotype.
It is difficult to determine whether these stellate and multinucleate fibroblasts are a functional or a degenerative change. Further studies are necessary to address these questions.


Conclusion

Our study suggests that the stellate and multinucleate cells of GCF have a fibroblast phenotype.


Acknowledgments

This study was supported by CNPq, FAPEMIG and PRPq-UFMG.


References

Bakos LH: The giant cell fibroma: a review of 116 cases. Ann Dent 5: 32-35, 1992
Cattoreti G, Pileri S, Panavicini C, Becker MHG: Antigen unmasking on formalin-fixed paraffin-embedded tissue sections. J Pathol 171: 83-98, 1993
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Jang JG, Jung HH, Suh KS, Kim ST: Desmoplastic fibroblastoma. Am J Dermatopathol 21: 256-258, 1999
Karabela-Bouropoulou V, Liape-Avgeri G, Mahera H, Magiassis V, Anagnostopoulos D, Bourli A, Kokka H, Sawa S: Giant cell fibroblastoma: an entity or a reactive phenomenon. Pathol Res Pract 195: 413-419, 1999
Magnusson BC, Rasmusson LG: The giant cell fibroma. A review of 103 cases with immunohistochemical findings. Acta Odontol Scand 53: 293-296, 1995
Odell E, Lock C, Lombardi T: Phenotypic characterization of stellate and giant cells in giant cell fibroma by immunocytochemistry. J Oral Pathol Med 23: 284-287, 1994
Pitt MA, Roberts ISD, Agambu JA, Eyden BP: The nature of atypical multinucleated stromal cells: a study of 37 cases from different sites. Histopathol 23: 137-145, 1993
Regezi JA, Zarbo RJ, Tomich CE, Lloyd RV, Coutney RM, Crissman JD: Immunoprofile of benign and malignant fibro-histiocytic tumors. J Oral Pathol 16: 260-265, 1987
Shi SR, Key ME, Kalra KL: Antigen retrieval in formalin-fixed paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39: 741-748, 1991
Swan RH: Giant cell fibroma. A case presentation and review. J Periodontol 59: 338-340, 1988
Weathers DR, Callihan MD: Giant cell fibroma. Oral Surg Oral Med Oral Pathol 37: 374-384, 1974
Weathers DR, Campbell WG: Ultrastructure of the giant cell fibroma of the oral mucosa. Oral Surg Oral Med Oral Pathol 38: 550-561, 1974


Correspondence: Dr. Ricardo Santiago Gomez, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Rua Conde Linhares, 141, 30380-030 Belo Horizonte, MG, Brasil. E-mail: rsgomez@net.em.com.br


Accepted August 20, 1999
Eletronic publication: April, 2000


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