Expression of transforming growth factor-ß in oral submucous fibrosis: A systematic review.

Oral submucous fibrosis (OSF) is a potentially malignant disorder characterised by inflammation and progressive fibrosis. Transforming growth factor-ß (TGF-ß) has been established as a master regulator of fibrosis in various organs; however, lack of systematic review on expression of TGF-ß and its isoforms in OSF restrict the understanding of their behaviour in its pathogenesis. Online electronic databases, such as PubMed Medline, Cochrane Library, Embase, and Scopus, were searched from their respective dates of inception till 31st March 2022. Human studies related to TGF-ß expression in histopathologically diagnosed OSF cases, with or without malignant transformation, were included and assessed using a Cochrane risk of bias assessment tool: For non randomised studies of interventions (ACROBAT NRSI). The electronic literature search yielded 394 articles. Of those, ten articles met the inclusion criteria and involved total of 579 OSF patients. The risk of bias (RoB) was low to moderate. These studies demonstrated a significant positive expression of TGF-ß and its isoforms in OSF compared to that in normal tissue samples. An increased pan TGF-ß expression was observed in the early stages of OSF, and an increased expression of TGF-ß1 and TGF-ß2 were seen in advanced stages of OSF. Stage wise expression of TGF-ß3 has not been discussed in the included studies. No significant relationship was observed between epithelial dysplasia and TGF-ß expression in OSF. The distinct pattern in the expression of pan TGF-ß, TGF-ß1 and TGF-ß2 in various stages of OSF indicates their different roles in OSF progression. We believe isoform targeted studies exploring stage wise expression of the marker will open new treatment avenues for OSF.

Interplay of Transforming Growth Factor-Beta 1 and 3 in the Pathogenesis of Oral Submucous Fibrosis and Its Malignant Transformation: An Immunohistochemical Study.

Introduction Oral submucous fibrosis (OSF) is a chronic and potentially malignant oral condition that poses a significant public health issue due to its insidious nature. Transforming growth factor-beta (TGF-ß) is a key player in the pathogenesis of OSF and is responsible for fibrosis. This study aims to investigate the relationship between the expression of TGF-ß1 and TGF-ß3 in OSF and its malignant transformation by using immunohistochemistry. Materials and method The present study comprised of 120 formalin-fixed paraffin-embedded tissue samples, which included 20 normal oral mucosa (NOM), 80 OSF (20 each of stage 1- 4), and 20 oral squamous cell carcinoma (OSCC) (10 each of OSCC with and without OSF), and were stained for TGF-ß1 and TGF-ß3 by immunohistochemistry. Data were analyzed using R software version 4.1.2, GraphPad Prism 9.3.1 (GraphPad Software, San Diego, CA, USA) and Excel (Microsoft Corp., Redmond, WA). Results TGF-ß1 immunoexpression was negative in NOM with no significant difference among OSF and OSCC (with or without OSF). TGF-ß3 was significantly higher in OSCC (with or without OSF) than in OSF, and no significant difference was noted between OSF and NOM and between OSCC and NOM. A significant increase was seen in TGF-ß3 compared to TGF-ß1 in NOM, OSF (stage 1- 4), and OSCC with and without OSF. Conclusion TGF-ß3 has higher immunoexpression levels than TGF-ß1 in NOM, OSF, and OSCC. We speculate that quantitative or qualitative TGF- ß3 may be inadequate to prevent or attenuate fibrosis in OSF patients. There is also a modicum of probability that TGF-ß3 has a preventive rather than causative role in OSF pathogenesis. The role of TGF-ß3 in OSF needs further clarification.

Efficacy of anti-desmoglein 1 and anti-desmoglein 3 levels by enzyme-linked immunosorbent assay compared to biopsy of chronic oral ulcerative diseases with positive Nikolsky's sign to diagnose oral pemphigus vulgaris with or without skin involvement: a retrospective institutional observational pilot study.

OBJECTIVE: We assessed the efficacy of anti-desmoglein 1 (anti-DSG1) and anti-DSG3 levels by enzyme-linked immunosorbent assay (ELISA) as a preliminary diagnostic test in the diagnosis of oral pemphigus vulgaris (OPV) with or without skin involvement compared to biopsy. STUDY DESIGN: We retrospectively analyzed data collected from 23 patients (mean age 45.13 years) who had presented with chronic oral ulcerations, desquamative gingivitis, and a positive Nikolsky's sign. We performed ELISA, histopathologic examination, and direct immunofluorescence (DIF) and then calculated the sensitivity and specificity of the results of ELISA, histopathology, DIF, and the presence of a positive Nikolsky's sign in diagnosis. RESULTS: The ELISA results showed that 18 patients had elevated anti-DSG3 levels, of whom 8 also had elevated anti-DSG1 levels. The histopathology results indicated that 18 patients had OPV, of whom 4 had oral lichen planus, and 1 had sub-epithelial blistering disease confirmed to be mucous membrane pemphigoid MMP by DIF. ELISA, histopathology, and DIF had a 100% sensitivity and specificity, and the presence of a positive Nikolsky's sign had a sensitivity and specificity of 100% and 78.26%, respectively. CONCLUSIONS: Measurement of anti-DSG1 and anti-DSG3 levels by ELISA warrants consideration as a first-line diagnostic test for early detection of OPV with or without skin involvement over biopsy.

A Comparative Clinicopathological Study of Giant Cell Tumour (GCT), Central Giant Cell Granuloma (CGCG) and Peripheral Giant Cell Granuloma (PGCG).

Objective: To evaluate and compare the clinicopathological features of giant cell tumour (GCT), central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG). Material and methods: From 2006 to 2016, all histopathologically diagnosed cases of GCT were retrieved from the Department of Pathology, T.N.M.C, Mumbai and CGCG and PGCG were retrieved from the Department of Oral Pathology, Nair Hospital Dental College, Mumbai. Statistical analysis of the clinicopathological features was done using SPSS v 21.0, IBM. Intergroup comparison of all variables was done using t test for two groups, whereas, Kruskal-Wallis test and one-way ANOVA were done for more than two groups. Results: Twelve cases of GCT, 31 cases of CGCG and 39 cases of PGCG were reported over 11 years. The mean age of occurrence for GCT, CGCG and PGCG was 30.41 years, 27.69 years and 34.03 years, respectively. GCT was seen in long bones and CGCG and PGCG showed mandible predilection. Histologically, GCT showed evenly distributed giant cells with aggregated nuclei, whereas CGCG and PGCG showed aggregated giant cells with evenly distributed nuclei. The mean value of the number of giant cells and nuclei within giant cells was maximum in GCT (27.33, 33.50) followed by CGCG (23.56, 15.51) and PGCG (21.45, 11.32). Conclusion: The clinicopathological differences between GCT, CGCG and PGCG suggest that each one of these entities represent biologically different lesions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01724-3.

Persistent Buccopharyngeal Membrane - A Systematic Review of Case Reports and Case Series.

OBJECTIVE: Persistent buccopharyngeal membrane (PBM) is a rare anomaly associated with failure of ecto-endodermal resorption of the buccopharyngeal membrane on the 26th day of intrauterine life. The current literature has insufficient information about PBM. DESIGN: Systematic Review. PATIENTS, PARTICIPANTS: Online electronic databases such as PubMed-MEDLINE, Embase, and Scopus were searched using appropriate keywords from the earliest available data until 30th August 2022, with no language restriction. Additional sources such as Google Scholar, major journals, gray literature, conference proceedings, and cross-referencing were also explored. MAIN OUTCOME MEASURES: The present systematic review evaluated and analysed the data available on PBM along with its treatment options and clinicopathological findings, prevalence, and prognosis of the patient. RESULTS: Thirty-four publications with 37 reported cases were included in this systematic review. The majority of patients had dyspnea (n = 18), followed by dysphagia (n = 10). Approximately 16 patients suffering from PBM reported orofacial abnormalities. Seventeen patients reported complete PBM, and 18 patients had partial PBM. The treatment modality followed by most patients (n = 15) was surgical excision of the membrane, along with stent placement in four patients. Oropharyngeal reconstruction was performed in four cases. The overall prognosis and survival rate of this rare condition is good. CONCLUSION: This review suggests that PBM is poorly understood, and the diagnosis of partial PBM is confirmed only when the patient complains of difficulty in breathing or eating. In-depth analysis and follow-up of the reported cases should be performed to diagnose the disease early so that clinicians can provide adequate treatment to the patients.

Schaumann bodies: The basophilic inclusion body.

Schaumann bodies are the inclusion bodies usually seen in sarcoidosis, but can also be found in other conditions like tuberculosis, chronic beryllium diseases and Crohn's diseases. Histopathologically, these bodies appear as round to oval shell-like basophilic calcifications usually considered to be as a residuum of lysosomal organelles activity.

Granular cell ameloblastoma as a solitary peripheral growth after twenty years of segmental resection of the mandible: A rare case of recurrence.

The ameloblastoma is a slowly growing, locally invasive, benign epithelial odontogenic neoplasm of the jaws with a high rate of recurrence if not removed adequately. We report an interesting case of granular cell ameloblastoma, which presented as a solitary, peripheral, soft tissue growth 20 years after initial segmental resection of the left mandible. The basal layer of oral mucosa could be the possible source of peripheral ameloblastoma in our case. In order to reduce the chances of recurrence, we suggest to incorporate mucosal stripping along with the conventional treatment as a mandatory rather than an elective procedure while treating ameloblastoma.

Analysis of 55 cases of adenomatoid odontogenic tumor in an Indian population and review of literature

Background: This study reviews the demographic, clinical and radiographic features of adenomatoid odontogenic tumor(AOT) diagnosed in an Indian population over 50 years and also evaluate and compare follicular AOT(F-AOT) and extra-follicular AOT(EF-AOT). Material and Methods: 55 diagnosed cases of AOT from 1971-2020 were studied retrospectively. The data regarding the age, sex, location, variant of AOT, duration, clinical features, radiographic appearance, treatment and recurrence were collected and analysed. Results: Of the 722 odontogenic tumors diagnosed, 7.6% were AOTs with higher prevalence of extra-follicular (67.3%) than follicular (32.7%) variant. All the tumors were intraosseous with a marked predilection for maxilla over mandible, ratio 2:1. The patients mean age was 19.8 years with slightly higher female predilection (male:female ratio - 1:1.5). The anterior region (76.4%) was more frequently affected and entire quadrant was involved in 21.8% cases. Clinically, asymptomatic, slow-growing swelling was seen in 81.8% cases with duration of 15 days to 10 years. Radiographically, AOT appeared as well-corticated radiolucent lesion. Canine was the most commonly impacted tooth. Recurrence was seen in 3 cases. Conclusions: Interestingly, in this series extra-follicular was twice more common than follicular AOT. Few cases involved the entire quadrant or crossed the midline of either jaws.(AU)

Non-Surgical Ciliated Cyst of the Maxilla - An Unconventional Variant.

The term surgical ciliated cyst of the maxilla is a designation for cysts of the maxillary sinus conventionally associated with surgery and trauma. Surgical ciliated cysts with a noncontributory history of surgery or trauma can pose a diagnostic challenge. We report an interesting case of ciliated cyst of the maxilla in a 54-year-old male patient. The present case provides a plausible explanation for the occurrence of ciliated cyst of the maxilla lacking history of surgery or trauma.

Oral Amelanotic Melanoma: A Systematic Review of Case Reports and Case Series.

Oral amelanotic melanoma (OAM) is a rare, non-pigmented mucosal neoplasm representing less than 2% of all melanoma. The present study analyses the available data on OAM and describes its clinicopathological features, identifying potential prognostic factors. Online electronic databases such as PubMed-Medline, Embase, and Scopus were searched using appropriate keywords from the earliest available date till 31st March 2021 without restriction on language. Additional sources like Google Scholar, major journals, unpublished studies, conference proceedings, and cross-references were explored. 37 publications were included for quantitative synthesis, comprising 55 cases. The mean age of the patients was 59.56 years, and the lesions were more prevalent in males than in females. OAM's were most prevalent in the maxilla (67.2%) with ulceration, pinkish-red color, nodular mass, and pain. 2 patients (3.36%) were alive at their last follow-up, and 25 were dead (45.4%). Univariate survival analysis of clinical variables revealed that age older than 68 years (p = 0.003), mandibular gingiva (p = 0.007), round cells (p = 0.004), and surgical excision along with chemotherapy & radiation therapy (p = 0.001) were significantly associated with a lower survival rate. Oral Amelanotic Melanoma is a neoplasm with a poor prognosis, presenting a 6.25% possibility of survival after 5 years. Patients older than 68 years, lesions in the mandibular gingiva, round cells, and surgical excision along with chemotherapy and radiotherapy, presented the worst prognosis. However, they did not represent independent prognostic determinants for these patients.

A comparative immunohistochemical analysis of cortactin in orthokeratinized odontogenic cyst (OOC), sporadic odontogenic keratocyst (OKC), and syndromic OKC.

OBJECTIVES: To evaluate and compare the immunohistochemical expression of cortactin in the epithelial lining of orthokeratinized odontogenic cyst (OOC), sporadic odontogenic keratocyst (OKC), and syndromic OKC. METHODS: Formalin-fixed paraffin-embedded tissue blocks of histopathologically diagnosed cases of OOC, OKC, syndromic OKC, normal buccal mucosa (NBM), and oral squamous cell carcinoma (OSCC) were examined for immunohistochemical expression of cortactin. Clear brown cytoplasmic and membranous staining was considered positive. RESULTS: A statistically significant difference was observed between OOC and syndromic OKC (p < 0.001), as well as between sporadic OKC and syndromic OKC (p < 0.001). Although not statistically significant, the expression of cortactin was slightly higher in the basal layer of NBM (mean = 0.47), OOC (mean = 0.27), sporadic OKC (mean = 0.47) syndromic OKC (mean = 1.53), and OSCC (mean = 0.67) than in the parabasal layers of NBM (mean = 0.27), OOC (mean = 0.20), sporadic OKC (mean = 0.47), syndromic OKC (mean = 1.27), and OSCC (mean = 0.60). CONCLUSION: The expression of cortactin in the basal layer may suggest the formation of invadopodia in the basal layer where the invasion mechanism occurs. This finding is further supported by the higher localization of cortactin in areas of epithelial budding and daughter cysts in syndromic OKC, thereby reaffirming its possible association with recurrence.

The Role of Increased Connective Tissue Growth Factor in the Pathogenesis of Oral Submucous Fibrosis and its Malignant Transformation-An Immunohistochemical Study.

Connective tissue growth factor (CTGF), a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins, is highly expressed in various organ fibrosis and several malignant tumors. Although a few studies have been conducted using CTGF in oral submucous fibrosis (OSF) and oral squamous cell carcinoma, no study has demonstrated its relation with various stages of OSF and its malignant transformation. The present study investigated the possible role of CTGF in the pathogenesis of OSF and its malignant transformation by using immunohistochemistry. Ten formalin-fixed paraffin-embedded tissue blocks, each of Stage 1 OSF, Stage 2 OSF, Stage 3 OSF, Stage 4 OSF, well- differentiated squamous cell carcinoma (WDSCC) with OSF and WDSCC without OSF were stained for CTGF by immunohistochemistry. Ten cases of healthy buccal mucosa (NOM) were included as controls. The present study demonstrated a statistically significant expression of CTGF in the epithelium and connective tissue of OSF and WDSCC with and without OSF cases against its complete absence in NOM. We observed an upregulation of CTGF expression from NOM to various stages of OSF to WDSCC with or without OSF. A gradual upregulation of the CTGF expression in various stages of OSF to WDSCC (with and without OSF) against its complete absence in NOM suggests that CTGF plays an important role in the pathogenesis of OSF and its malignant transformation.