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ORIGINAL ARTICLE  
Year : 2017  |  Volume : 60  |  Issue : 1  |  Page : 15-20
Histological evaluation of the possible transformation of peripheral giant cell granuloma and peripheral ossifying fibroma: A preliminary study


1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Eskişehir Osmangazi University, Eskişehir, Turkey
2 Department of Periodontology, Faculty of Dentistry, Ankara University, Ankara, Turkey
3 Gören Private Pathology Labratory, Private Gören Pathology Institution, Ankara, Turkey
4 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ankara University, Ankara, Turkey
5 Department of Pathology, Gülhane Military Medical Academy, Ankara, Turkey

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Date of Web Publication14-Feb-2017
 

   Abstract 

Aims: The objective of this study is to describe shared morphological features of peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF) in detail and discuss the possible relationship between them. Materials and Methods: Ten intermediate cases with features resembling to both POF and PGCG were selected and type 3 and 1 collagen immunostainings were performed for evaluation of the connective tissue maturation. Immunohistochemical staining percentage (SP) for stromal cells in the slides of POF and PGCG counterparts of intermediate lesions was scored as 1 when the SP was above 10%, 2 when the SP was above 25%, 3 when the SP was above 50% and 4 when the SP was above 75%. Staining intensity (SI) of immunuhistochemical staining was graded and scored as 1 - mild, 2 – moderate, and 3 - severe. An immunoreactivity score was calculated by multiplying SP and SI. Results: All intermediate lesions comprised osteoclast type multinucleated giant cells and partly mineralized hard tissue component. Parts of intermediate lesions resembling POF showed higher type 1 collagen immunoreactivity compared to the PGCG counterparts of intermediate lesions (P < 0.05). PGCG counterparts showed higher type 3 collagen immunoreactivity compared to the POF counterparts of the intermediate lesions (P < 0.05). Conclusion: POF may be a later stage lesion with morphologically more mature components. A possible transformation may be considered for these two lesions.

Keywords: Collagen type 1, collagen type 3, gingival overgrowth, peripheral giant cell granuloma, peripheral ossifying fibroma

How to cite this article:
Dereci , Akgün &, Celasun B, Öztürk A, Günhan &. Histological evaluation of the possible transformation of peripheral giant cell granuloma and peripheral ossifying fibroma: A preliminary study. Indian J Pathol Microbiol 2017;60:15-20

How to cite this URL:
Dereci , Akgün &, Celasun B, Öztürk A, Günhan &. Histological evaluation of the possible transformation of peripheral giant cell granuloma and peripheral ossifying fibroma: A preliminary study. Indian J Pathol Microbiol [serial online] 2017 [cited 2017 Apr 27];60:15-20. Available from: http://www.ijpmonline.org/text.asp?2017/60/1/15/200032



   Introduction Top


Reactive fibrous overgrowths of the oral mucosa are common tumor-like proliferations and they are usually defined as the result of abnormal healing processes. These nonneoplastic proliferations include a range of lesions such as peripheral ossifying fibroma (POF), peripheral giant cell granuloma (PGCG), focal fibrous hyperplasia, and pyogenic granuloma (PG).[1]

POF was previously called as peripheral fibroma with calcification or calcifying fibroblastic granuloma.[2],[3] They are usually gingival nodular masses and are regarded as reactive proliferations rather than a neoplasm due to their slow growth rate and nondestructive nature.[4],[5],[6] POF may be a sessile or pedunculated lesion and have pinkish-reddish color similar to the surrounding gingiva. Sometimes, the overlying mucosa may be ulcerated by masticatory press. It is a common concept that the lesion originates from the cells of periodontal ligament and is associated with local irritants, such as dental appliances, restorations, dental plaque, and calculus causing gingival injury.[5],[7],[8],[9] Most of them are smaller than 2 cm in diameter, though enormous ones have also been reported.[7],[8],[9],[10] Histologically, they are composed of cellular bundles of fibroblasts and collagen fibrils. Variable amounts of osteoclast type giant cells and foci of mineralized bone or cementum-like tissues are also present.[1] In some cases, giant cells may be numerous and the lesion may have features resembling those of PGCG.

PGCG is another common gingival overgrowth with uncertain pathogenesis. Similar to the POF, local irritants are possibly responsible for the occurrence of this lesion. Histologically; it consists of edematous, mitotically active, loose connective tissue proliferation, and numerous osteoclast-like multinuclear giant cells. In addition, hemosiderin accumulation with bleeding zones, an increased number of dilated vessels, chronic inflammatory cell infiltration, and bone formation may also be present.[11]

Oral mucosal overgrowths, particularly PGCG and POF, share histological features such as abnormal connective tissue proliferation with giant cells in varying amounts and focal bone formation. However, PGCG is composed of relatively more immature and loose components compared to POF. In some cases, there may be confusion in the histologic differentiation of these lesions. It seems likely that POF may be a later stage lesion with morphologically more mature components. It is also suggested that some PG cases may turn into a POF in the late regression stage.[12]

To our knowledge, only one case of hybrid POF-PGCG lesion has been reported so far.[13] In this study, we selected ten cases with histologic similarities to both POF and PGCG, among 112 cases of POF and 147 cases of PGCG. The evaluation of these intermediate and shared features is subjective and the lesions can be called as either POF or PGCG by other observers. Shared morphologic features of the lesions were described in detail and possible relationship between them were discussed.


   Materials and Methods Top


Study design

The data and histologic slides of a 112 cases of POF and 147 cases of PGCG diagnosed and treated between the years 1997 and 2012 were retrieved from the archieves of three institutions. Histologic slides were reexamined to define the shared features. Selection criteria were the presence of both loose and collagenized stroma, clusters of osteoclast type giant cells, and formation of bone or cementum within the same lesion [Figure 1]. Ten cases with features resembling to both POF and PGCG were selected.
Figure 1: Intermediate case, with peripheral ossifying fibroma and peripheral giant cell granuloma-like areas which contain loose and collagenized cellular stroma, clusters of osteoclast type giant cells (black arrows) and bone or cementum formation (H and E, ×100)

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POF was assumed to be a late stage or more mature lesion than PGCG. For evaluation of connective tissue maturation, the quantity of loose or collagenized cellular connective tissue stroma was assessed. In addition, the amount of osteoclast type giant cell clusters were noted. For further comparison of connective tissue maturation, type 1 and 3 collagen fibril immunostainings were evaluated semiquantitatively. The hypothesis of this evaluation was based on the fact that the type 3 collagen is typical element of granulation tissue and it is produced by young fibroblasts during early regeneration. The tougher type collagen 1 is considered to be typical of scar tissue and the final product during repair.

Immunohistochemical staining

Sections of 6 μm were taken from each paraffin block of 10 cases of the selected lesions. The streptavidin-biotin technique was used to analyze the immunohistochemistry reactions for collagen type 1 and 3 (type 1: Polyclonal, LifeSpan Biosciences, LS-B342., type 3: Polyclonal, LifeSpan Biosciences, LS-B693). Detection of the primary antibody was performed using the LSAB Kit (DakoCytomation, Carpinteria, CA, USA). Sections were incubated with biotinylated secondary antibody. Antibody-horseradish peroxidase complex was visualized by incubation with diaminobenzidine. Slides were briefly counterstained in Harris hematoxylin and covered.

In microscopical examination, four high-power, nonoverlapping, relatively cellular random fields were chosen under ×40 magnification in the slides of POF and PGCG counterparts of the intermediate lesions. Slides were evaluated by one researcher. Staining percentage (SP) and staining intensity (SI) scores were established for each selected microscopic areas. SP was scored as 1, when the SP of stromal cells in the selected area was above 10%, 2 when the SP was above 25%, 3 when the SP was above 50% and 4 when SP was above 75%.[14] The percentage of positively and clearly stained stromal cells was assessed. According to the density, extensity, and homogenity of staining, SI was semiquantitatively graded and scored as 1 - mild, 2 – moderate, and 3 - severe. Immunoreactivity score (IS) was obtained by multiplying SP and SI scores (IS = SP × SI) for each randomly selected area.[15] Mean IS value for randomly selected areas was calculated for each counterpart of intermediate lesions.

Statistical analysis

SPSS version 20.0 (IBM, Chicago, IL, USA) was used for statistical analysis. A Shapiro–Wilk's test (P < 0.05) and a visual inspection histograms, normal Q-Q plots and box plots showed that the mean ISs were not normally distributed. A nonparametric Mann–Whitney U-test was performed to assess the significance of the difference between mean ISs of POF and PGCG counterparts for type 1 and 3 collagen staining. P < 0.05 was considered statistically significant.


   Results Top


Clinical features

Summary of clinical data and histologic findings of the 10 cases is shown in [Table 1]. Mean age was 25 ± 8.7. All cases shared a similar clinical appearance with exophytic, pedunculated or sessile, pinkish gingival overgrowths. All cases had been treated with surgical excision. No information about recurrence was recorded.
Table 1: Main clinical and histological data of selected ten cases

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Histopathological features

The selected cases had increased connective tissue stroma with spindle fibroblastic cells and contained collagen bundles throughout the proliferation [Figure 2]. There was also nodular aggregation or randomly distributed osteoclast type multinucleated giant cells within or around the connective tissue proliferation. Small trabeculae of nonlamellated bone or cementum like, partly mineralized hard tissue component were seen in all of the slides. Rarely, focal hemorrhage and mild subepithelial lymphocyte infiltration were seen. Two of the cases had ulceration of the overlying mucosa [Table 1].
Figure 2: Peripheral ossifying fibroma-like and peripheral giant cell granuloma-like components can be clearly seen in the transition area of the intermediate lesion. Numerous spindle fibroblastic cells are spread throughout increased collagenized connective tissue stroma in the peripheral ossifying fibroma-like component (H and E, ×200)

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Mean IS scores calculated for all cases were demonstrated in [Table 2]. Parts of the intermediate lesions resembling POF generally showed grade 2–3 SI for type 1 collagen [Figure 3] and [Figure 4]. However, parts resembling PGCG, were characterized by grade 1 SI for type 1 collagen [Figure 4]. Diffuse grade 1 SI for type 3 collagen was observed in POF counterparts of the intermediate lesion [Figure 5]. PGCG counterparts generally showed grade 3 SI for type 3 collagen [Figure 6]. Type 1 collagen immunoreactivity of POF counterparts was significantly higher compared to PGCG counterparts (P < 0.05). Type 3 collagen immunoreactivity of PGCG counterparts in intermediate lesions was significantly higher compared to POF counterparts (P < 0.05).
Table 2: Immunoreactivity score was calculated by multiplying staining percentage and staining intensity scores which were scored by one researcher for each counterpart of the hybrid lesions

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Figure 3: Type 1 collagen staining is more intense (grade 3) in peripheral ossifying fibroma counterpart of the mixed lesion. Staining intensity of peripheral ossifying fibroma counterpart is equvalent with submucosal staining intensity (IHC, ×200)

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Figure 4: Peripheral giant cell granuloma counterpart (left side of the slide) of the mixed lesion shows grade 1 staining intensity for type collagen. However, peripheral ossifying fibroma counterpart (right side of the slide) of the mixed lesion shows grade 2 staining intensity for type 1 collagen (IHC, ×200)

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Figure 5: Peripheral ossifying fibroma counterpart of the mixed lesion shows grade 1 staining intensity for type 3 collagen. Staining intensity of peripheral ossifying fibroma counterpart is lower than submucosal staining intensity (IHC, ×100)

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Figure 6: Grade 3 staining intensity for collagen is observed in the peripheral giant cell granuloma counterpart of the mixed lesion. Type 3 collagen is more prevalent in the peripheral giant cell granuloma counterpart (IHC, ×200)

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   Discussion Top


POF and PGCG are common, probably reactive, tumor-like oral mucosal overgrowths. PGCG was called as “reperative giant cell granuloma” reflecting the concept that it is nonneoplastic and is result of an abnormal regenerative process. Several previous reports suggested that PGCG might be neoplastic due to the recurrences and histological appearances.[16],[17],[18],[19]

POF is also considered as a nonneoplastic lesion. POF is different from jaw bone ossifying fibroma which is a neoplastic lesion. In fact, POF is quite similar to peripheral odontogenic fibroma, which is also different from central odontogenic fibroma.[7],[20],[21] Buchner et al.[7] suggested that it might be difficult to establish the diagnosis when the POF is in its early stage, in which the lesion consists mostly of cellular fibroblastic tissue and foci of mineralization. As a result, the lesion may be missed or misdiagnosed by the pathologist. Prasad et al.[12] stated that a recurred lesion which had been originally diagnosed as POF might actually be a PG and these two lesions may be components of the same histopathologic spectrum.

Sometimes, it can be challenging to differentiate a POF from PGCG, both clinically and histologically since they share many features. Histologically, lamellar or woven bone, can be seen in especially the older lesions of PGCG. Bone trabeculae seen in PGCG usually show continuity with the underlying alveolar bone. Dayan et al.[11] reported that 35% of their 62 PGCG cases contained mineralized material and the source of the mineral was predominantly lamellar host bone. It is suggested that mineralization in the lesion can be due to the presence of mononuclear stromal cells of PGCG that are considered to be latent proliferative osteoblasts.[22],[23] Bone or cementum-like material that is seen in POF is usually nonlamellated and shows no connection with the alveolar bone.

Morphological similarities seen in the present cases suggest that these two lesions may transform into each other [Figure 1]. Some long-standing cases of PGCG can contain more bone tissue. However, we do not have information regarding the factors that trigger this transformation. Buchner et al.[7] also suggested that the specific histopathological features of reactive lesions of the gingiva may evolve as the lesion gets older.[7]

POF has a very peculiar mesenchymal component with spreading bundles of fibroblasts and collagen fibers. It is unusual to find this component in typical PGCG cases. Most of the selected intermediate lesions in our series contained numerous osteoclast type giant cells in connective tissue and also contained nodules of them as seen in PGCG. However, the number of giant cells were not as much as in PGCG cases. Additionally, ulceration of the overlying epithelium and inflammatory cell infiltration within the lesion is less frequent in POF cases compared to PGCG. This observation supports the hypothesis that POF may be the more mature and late stage of the proliferative lesion.

Collagen type 1 forms the main component of bone and tendons and has great resistance to the tension forces.[24] On the other hand, collagen type 3 is organized as a loose mesh.[25] During the early and immature phases of wound healing, there is an increase in the deposition of collagen type 3.[26] Based on these data, collagen type 1 and 3 immunostainings were also performed to evaluate the maturity of each lesions in the current study. Higher SI for collagen type 1 in POF-like areas compared to PGCG-like areas in selected intermediate cases suggests that the stroma of POF is more organized and firm (P < 0.05). Accordingly, SI for type 3 collagen in PGCG-like regions in intermediate lesions was observed higher than POF-like areas (P < 0.05).

The main clinical and demographic information in our cases such as site, age distribution, and gender predilection are consistent with those of the previously reported series.[4],[5],[7] These variables are of no help for the differential diagnosis. Both POF and PGCG are usually exophytic gingival overgrowths and they may have no direct relation with jaw bones. Ossification in gingival lesions of both POF and PGCG is metaplastic in nature and they probably occur due to similar inorganized regenerative processes. Heterotopic calcification and ossification within a connective tissue may be a sign of previous injury and seem as neutralizing processes.

In this study, we tried to focus on intermediate lesions which show similar histological characteristics of both the POF and the PGCG. Reactive overgrowths of the gingiva are regarded as closely related processes with similar etiology such as chronic inflammatory irritation and trauma. However, the clinical and histological presentations may be different. Some authors suggested that it may be logical to consider that the reactive lesions can transform into each other under several precipitating factors or changes in physiological mechanisms such as aging of the lesion.[6],[12],[22] A hypothesis of transformation between POF and PGCG can be supported by the histopathological evidence which we obtained from these 10 cases. However, a solid understanding of the linkage between these lesions still remains elusive. Larger case series of mixed or intermediate POF-PGCG lesions are needed to investigate potential factors responsible from overlapping histopathologic features. These are also needed to understand whether these lesions can show transformation into another. The duration of these lesions can be another factor contributing to the morphologic appearances. At the present state, we might assume that at least some cases of POF might have started as lesions with histopathological features of PGCG.

Acknowledgment

The authors thank Dr. Olgu Nur Dereci for statistical analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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Correspondence Address:
mr Dereci
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Eskişehir Osmangazi University, Meşelik Campus, 26480 Eskişehir
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.200032

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
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