OBJECTIVE: To explore the role of fibrocytes in the recurrence and calcification of fibrous epulides.
METHODS: Different subtypes of fibrous epulides and normal gingival tissue specimens were first collected for histological and immunofluorescence analyses to see if fibrocytes were present and whether they differentiated into myofibroblasts and osteoblasts upon stimulated by transforming growth factor-β1 (TGF-β1). Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human peripheral blood mononuclear cells (PBMCs) were subsequently isolated from in vitro models to mimic the microenvironment in fibrous epulides to identify whether TGF-β1 as well as the calcium and phosphorus ion concentration in the extracellular matrix (ECM) of a fibrous epulis trigger fibrocyte differentiation.
RESULTS: Fibrous epulides contain fibrocytes that accumulate in the local inflammatory environment and have the ability to differentiate into myofibroblasts or osteoblasts. TGF-β1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner, while TGF-β1 stimulates the fibrocytes to differentiate into osteoblasts when combined with a high calcium and phosphorus environment.
CONCLUSIONS: Our study revealed fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the inhibition of recurrence of fibrous epulides.

UNASSIGNED: Understanding the role of hormones in periodontitis is important. Periodontal microscopic surgery approach in the treatment of fibrous epulis is not indicated. Wider flap access with root planning is indicated to control the lesion in one phase.
UNASSIGNED: We present a case of a 40-year-old female who presented with a gingival hyperplastic lesion around the maxillary left permanent central and lateral incisors. Patient\'s medical history reveals a recent pregnancy, hypothyroidism, ulcerative colitis, and schizoaffective disorder. All medical conditions were controlled by medications. The lesion was excised using a minimally invasive periodontal surgical technique, and the biopsy results confirmed a diagnosis of ulcerative fibrous epulis with osseous metaplasia. No curettage or local debridement was done under the assumption that the patient\'s oral hygiene was satisfactory and due to aesthetic concerns of gingival recession and creation of black triangles. The lesion recurred after 3 months and was removed using a traditional more invasive surgical technique. The patient was followed up for 2 years, and there was no further recurrence due to the complete excision of the lesion in the second surgery and the disappearance of the hormonal-related factors post-pregnancy that could have contributed to the gingival hyperplasia. The unique component of the case we are presenting is the comparison between two different surgical techniques and the conduction versus absence of local periodontal debridement after surgical excision as well as the possible correlation between oral supplements and the calcific nature of the lesion(s) reported. The case we present demonstrates that a more invasive traditional surgical approach together with local periodontal therapy provide an optimum treatment outcome in conjunction with elimination of any associated etiological factors. We also propose that hormones are more important as an etiological factor in developing fibrous epulis lesions than medical conditions and medications.

The association between clinicopathologic characteristics and the relapse of fibrous gingival hyperplasia is unknown.
The records of 211 consecutive patients with a clinicopathologic diagnosis of fibrous gingival hyperplasia were retrieved. Patients who experienced relapse after surgical excision of the lesion were considered case patients (n = 30). All control patients were informed that there was no recurrence (n = 181). Logistic regression was used to evaluate the associations among different characteristics and the recurrence. Stratified analyses on sex was applied to identify the different associations.
Binary logistic regression showed that patients with ulcer (odds ratio [OR], 3.23; 95% CI, 1.18 to 8.83) or mechanical stimulation (OR, 2.42; 95% CI, 1.03 to 5.68) had a higher risk of experiencing recurrence. Stratified analysis of sex identified significant association in females (ulcer: OR, 4.04; 95% CI, 1.14 to 14.34; mechanical stimulation: OR, 3.30; 95% CI, 1.15 to 9.42). No significant difference was observed in males (ulcer: OR, 2.44; 95% CI, 0.40 to 15.06; mechanical stimulation: OR, 1.62; 95% CI, 0.28 to 9.40). Male patients with larger epulides had fewer recurrence (OR, 0.13; 95% CI, 0.02 to 0.74). There was no significant difference in pathologic calcification between case and control patients (P > .05).
Patients with ulcer and mechanical stimulation may have a high risk of experiencing recurrent epulis.
More attention should be paid to patients with ulcer and mechanical stimulation. Apart from complete surgical removal, it is important to remove local stimulation to prevent recurrence of these lesions.

OBJECTIVE: Epulis is considered to be a massive reactive lesion rather than a true neoplasia. AhR is thought to be associated with inflammation and development of neoplasms. Here, we aimed to observe the expression of AhR in fibrous epulis and explore its role and possible mechanism in the pathogenesis of epulis.
METHODS: Epulis and normal gingival tissues were collected, and AhR expression was detected at the mRNA and protein levels by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. The expression levels of proinflammatory cytokines and apoptosis-related factor genes in human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs) transfected with AhR short interfering RNA (siRNA) or negative control siRNA, upon stimulation with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS), were then examined. Finally, the expression levels of the proinflammatory cytokines and apoptosis-related factor genes in the epulis tissues were observed by qPCR.
RESULTS: AhR expression in fibrous epulis was significantly increased at both the mRNA and protein levels. The expression of proinflammatory cytokines and apoptosis-related factor genes in hPDLCs transfected with AhR siRNA was significantly decreased when stimulated with Pg-LPS. The same trends were observed for hGFs. The opposite trend was detected in the epulis tissues.
CONCLUSIONS: AhR may be a key factor in fibrous epulis pathogenesis that acts by regulating the expression of BCL2 family genes and inflammatory factor-related genes.

BACKGROUND: The pathogenesis of fibrous epulis is still quite unclear. Our recent genome-wide RNA sequencing analysis revealed that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway regulates the expression of Bcl-2 family and IAP family genes, leading to increased proliferation and the inhibition of apoptosis. The PI3K/AKT signaling pathway can promote autophagy in human gingival fibroblasts; therefore, the purpose of the present study was to identify whether autophagy is involved in the pathogenesis of fibrous epulis.
METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were identified using the PCR array. The expression levels of eighteen autophagy-related (ATG) family genes, twelve B-cell lymphoma 2 (Bcl-2) family genes, and eleven cysteine-dependent aspartate-directed protease (caspase) family genes were validated using quantitative real-time PCR (qRT-PCR). Autophagy induction was determined by measuring microtubule-associated protein light chain 3 (LC3) conversion (LC3-I to LC3-II) by immunoblot analysis.
RESULTS: The PCR array identified six upregulated genes, whereas no genes were expressed at significantly lower levels. The upregulated genes were BCL2, BCL2L1, CXCR4, HSP90AA1, HSPA8, and IGF1, which all belong to the \"regulation of autophagy\" group but not the \"autophagy machinery components\" group. qRT-PCR verified that the expression levels of BCL2, BCL2L1 (also known as BCL-XL), and BCL2L2 (also known as BCL-W) were significantly increased in fibrous epulis. No LC3-I to LC3-II conversion was observed.
CONCLUSIONS: The present study reveals that in fibrous epulis, Bcl-2 and Bcl-xL coordinately mediate gingival cell escape from apoptosis, leading to uncontrolled proliferation. Moreover, ATG family genes are not activated, and autophagy is not involved in this process.

Ossifying and non-ossifying peripheral oral fibromas (POF) of the gingival and alveolar mucosa are localized, cellular, small fibrous nodular lesions likely resulting from diverse external/ internal physical and chemical irritation or injuries. A central nidus of metaplastic woven bone characterizes and defines the ossifying variant. The inherent tendency of these lesions to ossify remains elusive. We herein analyze SATB2 expression as osteoblastic transcription and differentiation factor in 28 gingival POFs (10 of them ossifying) and compare them to 28 fibrous lesions from different non-gingival intraoral sites. Strong to moderate diffuse nuclear SATB2 immunoreactivity was detected in all ossifying (10/10; 100%) and in 8/18 (44%) non-ossifying gingival POFs, but in only 1/28 (3%) non-gingival oral reactive nodular fibrous lesions. This study illustrates for the first-time consistent expression of the osteoblastic marker SATB2 in ossifying and most of non-ossifying POFs of the gingival area but lack of this marker in reactive fibrous lesions from other oral cavity sites. This finding is in line with the proposed origin of gingival POFs from periodontal ligaments and may explain the frequent ossification observed in them. It is mandatory to consider this finding when assessing biopsies from SATB2-positive oral cavity neoplasms to avoid misinterpretation.

BACKGROUND: Epulis has a tumor-like appearance but is considered to be a massive reactive lesion rather than a true neoplasia. Limited information about the pathogenesis of epulis is available. The purpose of our study was to identify potential signaling pathways in fibrous epulis through transcriptome profiling.
METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were detected using RNA sequencing (RNAseq). The expression levels of eighteen genes were validated using quantitative real-time PCR (qRT-PCR).
RESULTS: RNAseq identified 533 upregulated genes and 732 downregulated genes. The top 10 upregulated genes were IL11, OSM, MMP3, KRT75, MMP1, IL6, IL1B, IL24, SP7, and ADGRG3. The top 10 downregulated genes were BCHE, TYR, DCT, KRT222, RP11-507K12.1, COL6A5, PMP2, GFRA1, SCN7A, and CDH19. KEGG pathway analysis further indicated that the DEGs were enriched in \"Pathways in cancer\" and the \"Ras signaling pathway\". quantitative real-time PCR verified that the expression levels of SOS1, HRAS, PIK3CA, AKT3, IKBKA, IKBKB, NFKB1, BCL2, BCL2L1, XIAP, BIRC2, and BIRC3 were increased significantly.
CONCLUSIONS: The current transcriptomic profiling study reveals that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes, leading to increased proliferation and apoptosis inhibition.

Peripheral odontogenic fibroma (POF) is a relatively rare odontogenic tumor of the gingiva. Although its histological differential diagnosis from fibrous epulis (FE) is important, no study has reported the differences in their expression of immunohistochemical markers. Here, we compared the expression of tumor markers that are frequently used for the differential diagnosis of fibroproliferative lesions between POF and FE.
Forty cases were selected, including 20 POF and 20 FE cases. CD34, B cell lymphoma (Bcl)-2, and Ki-67 were used as markers for immunohistochemical examination. The positive cell ratio was calculated, and Mann-Whitney U test was performed for statistical analysis.
POF and FE were negative for CD34 expression but showed Bcl-2 and Ki-67 expression. The ratio of Bcl-2- and Ki-67-positive cells was significantly higher in POF than in FE (p < 0.001).
POF is CD34 negative, and Bcl-2 and Ki-67 positive-cell ratio differs between POF and FE, suggesting that these proteins may serve as immunohistochemical markers for the differential diagnosis of POF.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable \"periodontitis patient\" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a \"case\" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable \"periodontitis patient\" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a \"case\" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.