|Year : 2019 | Volume
| Issue : 2 | Page : 123-126
Quantification of mast cells in reactive oral lesions – A clue to the morphologic diversity
Saurabh Shekar1, Punnya V Angadi2
1 Department of Dentistry, Anugrah Narayan Magadh Medical College and Hospital, Gaya, Bihar, India
2 Department of Oral Pathology and Microbiology, KLEVK Institute of Dental Sciences and Hospital, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
|Date of Web Publication||4-Jun-2019|
Dr. Punnya V Angadi
Department of Oral Pathology and Microbiology, KLEVK Institute of Dental Sciences and Hospital, KLE Academy of Higher Education and Research, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
OBJECTIVE: Inflammatory fibrous hyperplasia (IFH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF), and peripheral giant cell granuloma (PGCG) are common oral soft-tissue reactive lesions that correspond to excessive connective tissue proliferation as a reaction to trauma or irritational factors local to the oral cavity. These lesions have specific differences in their histopathologic appearances and behavior in spite of having common etiologic factors. Mast cells (MCs) are immune-regulatory cells that have an important role to play in oral inflammation and have also been associated with tissue remodeling and fibrosis in various disorders.
METHODOLOGY: MCs were stained with toluidine blue in cases of IFH (20), PG (20), PGCG (20), and POF (20) along with normal gingiva tissue as control (5) for quantification and comparison among them.
RESULTS: The mast cell count was low in normal mucosa but a progressive increase was seen from PGCG to IFH to POF with maximum mast cells were evident in PG. There was a significant difference noted in the MC counts between the normal mucosa and the oral reactive lesions (P < 0.05). However, the difference in the MC count did not reach statistical significance among the reactive lesions (P = 0.400).
CONCLUSION: MCs emerged as significant players in the pathogenesis and histopathologic diversity of oral reactive lesions by their effects on fibroblasts and endothelial cells.
Keywords: Inflammatory fibrous hyperplasia, mast cell, oral reactive lesions, peripheral giant cell granuloma, peripheral ossifying fibroma, pyogenic granuloma
|How to cite this article:|
Shekar S, Angadi PV. Quantification of mast cells in reactive oral lesions – A clue to the morphologic diversity. Indian J Health Sci Biomed Res 2019;12:123-6
|How to cite this URL:|
Shekar S, Angadi PV. Quantification of mast cells in reactive oral lesions – A clue to the morphologic diversity. Indian J Health Sci Biomed Res [serial online] 2019 [cited 2019 Aug 24];12:123-6. Available from: http://www.ijournalhs.org/text.asp?2019/12/2/123/259637
| Introduction|| |
Reactive lesions affecting the oral mucosa are considered to be frequent lesions occurring in the oral cavity. Most of these lesions represent excessive connective tissue proliferation as a reaction to trauma or irritational factors local to the oral cavity. These lesions have specific differences in their histopathologic appearances and behavior in spite of having common etiologic factors. The main lesions included in this spectrum are inflammatory fibrous hyperplasia (IFH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF), and peripheral giant cell granuloma (PGCG). Histologically, IFH is characterized by abundant collagen with epithelial hyperplasia in a background of chronic inflammatory cells, while POF in addition has proliferating spindle-to-ovoid cells with metaplastic bone formation. PG has extensive proliferation of endothelial cells with numerous microvessels in an edematous connective tissue intermixed with acute and chronic inflammation; PGCG shows the presence of multinucleated giants cells dispersed in a cellular stroma of proliferating spindle-to-round cell associated with numerous blood vessels and extravasated red blood cells.
Mast cells (MCs) are granular immune cells originating from the bone marrow. They are also known as “unicellular endocrine glands” as they can release numerous chemical components with potent biological action on various target tissues. They are key players in oral inflammation and secrete numerous inflammatory mediators and vasoactive agents that have been associated with tissue remodeling and fibrosis in various disorders.,
The intricate communication between MCs and fibroblasts has been studied extensively which suggests that these interactions could contribute to excessive collagen deposition predisposing to fibrotic disorders such as scleroderma, renal fibrosis, and keloids. This interrelation has also been implicated in oral submucous fibrosis, gingival enlargements, as well as in fibrotic changes in the salivary glands.,,,, Thus, activation of MCs may be a distinctive attribute observed in chronic inflammatory reactions progressing to fibrosis due to increased collagenization.,, Thus, it appears that MCs may be responsible for the varied histopathologic appearance and progression of the lesions.
The present study aimed to quantify the MCs in oral reactive lesions to assess their possible role in the development and morphologic diversity of these lesions.
| Methodology|| |
After obtaining the Institutional Ethical Clearance, the study included 80 cases of previous histopathologically diagnosed cases of oral reactive lesion, i.e., IFH (20), PG (20), PGCG (20), and POF (20) along with normal gingiva tissue as control (5) (obtained while surgical removal of impacted third molars). Formalin-fixed and paraffin-embedded tissue blocks of the included cases and controls were retrieved from the archives of the Department of Oral Pathology and Microbiology.
Two sections of 4 μm each were obtained from each block and stained with routine hematoxylin and eosin as well as with 1% toluidine blue for MCs.
Preparation of toluidine blue
One percent of toluidine blue was taken in 50% of isopropanol. MCs stained metachromatically purple on using toluidine blue due to sulfated proteoglycans present in the secretory granules.
Connective tissue MCs in ten high-power fields were counted by two independent observers using microscope. The entire section was examined thoroughly, and ten fields with maximum number of MCs were selected and MCs were counted in all these ten fields. The total count in all the fields was considered as MC count for that case.
Descriptive statistics, i.e., mean and standard deviation will be generated, and the data were analyzed using Students t-test and on one-way analysis of variance.
| Results|| |
Connective tissue showed that the presence of MCs was seen, especially localized in the vicinity of the blood vessels and sometimes scattered throughout the connective tissue. They appeared purple and granular mononucleated round-to-ovoid cells. The MC count showed variation among the study groups [Table 1].
|Table 1: Mean and standard deviation of mast cell counts in various oral reactive lesions|
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The mast cell count was low in normal mucosa but a progressive increase was seen from PGCG to IFH to POF with maximum mast cells were evident in PG. There was a significant difference noted in the counts of MCs among the oral reactive lesions and normal mucosa (P < 0.05). However, the difference in the MC count did not reach statistical significance among the reactive lesions (P = 0.400) [Figure 1] and [Figure 2].
|Figure 1: Mast cells evident as purple metachromatic cells in inflammatory fibrous hyperplasia and peripheral giant cell granuloma|
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|Figure 2: Abundant purple-stained mast cells pyogenic granuloma and peripheral ossifying fibroma|
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| Discussion|| |
MCs are granular immune-regulatory cells that are derived from the bone marrow found usually in the connective tissue of most mucosa as well as in the nervous systems. MCs on activation by various stimuli release from their granules numerous inflammatory mediators, cytokines, interleukins (ILs), vasoactive compounds, and enzymes that play an important role in tissue inflammation and its sequelae. The granules of the MCs stain metachromatically purple with toluidine blue as evidenced on light microscopic visualization.,
The mediators released by the MCs can stimulate, inhibit, or have toxic effects on the surrounding cells with resultant inflammatory reaction in the oral mucosa as well as in numerous other target tissues. The key mediators released by MCs include serine proteases tryptase, chymase, histamine, heparin, serotonin, acid hydrolases, tumor necrosis factor-alpha (TNF-alpha), and IL-16.,,,
Oral reactive lesions occur in response to local irritation and are characterized by neovascularization, inflammation, and fibrosis depending on the stage of development as well as metaplastic bone formation. In this study, the MC counts were significantly higher in the oral reactive lesions as compared to normal mucosa suggesting that MCs are upregulated in these lesions predisposing to the inflammatory reaction and the pathogenesis of these lesions.,
The maximum MC count was evident in PGs and POF followed by IFH and least in PGCG. This highlights the varied role played by MCs in these individual lesions. There was, however, no statistically significant difference noted among the reactive lesions similar to that reported by Parizi et al. and Farahani et al.
In IFH, the enhanced MC count in a background of fibrosis may signify the interaction of MCs and the fibroblasts, predisposing to release of factors responsible for fibrosis. MCs can activate fibroblasts through tryptase thus enhancing collagen synthesis by production of hyaluronic acid. In addition, enhanced release and expression of chymase leading to activation of transforming growth factor (TGF-beta) has also been implicated in fibrosis of the lung, skin, and kidneys as well as in scleroderma and bladder fibrosis.,,,
In POF, the MCs in addition to stimulation of fibroblasts through release of TGF-beta may release bone morphogenetic protein-4 which may predispose to ossification. This is corroborated by studies that have shown the association between increased MC counts with heterotopic ossification in patients with fibrodysplasia ossificans progressiva. The MCs may thus predispose to fibrosis and bony metaplasia.
In PG, MCs may contribute to the vascularity by release of several angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, TNF-alpha, IL-8, and heparin, leading to endothelial proliferation and neoangogenesis.
The low MC count observed in PGCG is in concordance with Parizi et al. and Farhadi et al. The MCs have been shown to interact with fibroblasts and involved in morphogenesis of multinucleated giant cells which are thought to arise from the endothelial cell precursors. In addition, they may be responsible for the angiogenesis and vascularity evident in this lesion.
| Conclusion|| |
MCs have an important role in the pathogenesis and histopathologic diversity of oral reactive lesions by their effects on fibroblasts and endothelial cells. However, the interaction of MCs with other connective tissue components validates further study at the molecular level. In addition, future studies can highlight on evaluating the MCs role in the clinical course and aggressiveness of these reactive lesions.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]