A Preliminary Study of the Role of Endothelial-Mesenchymal Transitory Factor SOX 2 and CD147 in the Microvascularization of Oral Squamous Cell Carcinoma.

INTRODUCTION: The aim of this study was to detect the possible endothelial expression of embryonic-type cancer stem cells (CSC) marker SOX2 and the stemness-type CSC marker CD147 in oral potential malignant disorders (OPMDs), oral leukoplakia (OL) in particular, and oral squamous cell carcinoma (OSCC). METHODS: This study focuses on the immunohistochemical pattern of expression of CSC protein-biomarkers SOX2 and CD147 in paraffin-embedded samples of 21 OSCCs of different grades of differentiation and 30 cases of OLs with different grades of dysplasia, compared to normal oral mucosa. RESULTS: The protein biomarker SOX2 was expressed in the endothelial cells, but without establishing any statistically significant correlation among OSCC, OL, and normal tissue specimens. However, SOX endothelial staining was noticed in 7/30 (23.3%) cases of OL (one non-dysplastic, one mildly dysplastic, one moderately dysplastic, and four severely dysplastic cases) and 5/21 (23.8%) cases of OSCC (two well-differentiated, one moderately differentiated, and two poorly differentiated cases). Although CD147 is expressed in normal oral epithelium, OL, and OSCC neoplastic cells, its vascular-endothelial expression was noticed in only 2/5 (40%) cases of normal oral epithelium, 1/30 (3.3%) cases of OL (one severely dysplastic case), and 4/21 (19%) cases of OSCC (two well-differentiated, one moderately differentiated, and one poorly differentiated case). Therefore, no statistically significant correlation among OSCC, OL, and normal tissue specimens was established. CONCLUSION: The endothelial presence of SOX2 both in oral potentially malignant and malignant lesions suggests that SOX2 may be implicated in the microvascularization process and associated with the degree of dysplasia in OL. The expression of CD147 may be attributed both to local inflammation and tumorigenesis. The implementation of CD147 in larger groups of tissue samples will shed some light on its role in cancer and inflammation. The evidence so far supports the need for more studies, which may support the clinical significance of these novel cancer stem cell biomarkers.

Gingival Enlargement Can Constitute the Only Diagnostic Sign of Leukemia: Report of an Unusual Case.

Gingival hyperplasia may arise due to microbial-related local irritation, mouth breathing, drug administration, genetic disorders, leukemia, Wegener granulomatosis, Crohn's disease, and sarcoidosis. The background may be inflammatory, fibrotic, or combined. The aim of this study was to present the diagnostic procedure for a case of gingival enlargement, which was the only sign of a severe systemic disease in a young male adult. The patient was referred, complaining of persistent gingival bleeding in the posterior area of the maxilla, bilaterally. Clinically, a diffuse gingival enlargement was noticed without regional lymphadenopathy. The histopathological examination revealed abundant neoplastic cells of hemopoietic origin with strong and diffuse positivity for CD45 and CD68, and in addition, scattered neoplastic cells exhibited mild to moderate positivity for c-kit (CD117), indicating the diagnosis of acute myeloid leukemia, which diffusely infiltrated the lamina propria of the gingiva. The numerous conditions leading to gingival enlargement other than gingivitis or periodontitis are a diagnostic challenge in clinical practices. From this point of view, the role of the dentist is crucial when commencing the diagnosis of severe systemic diseases like leukemia.

"Shot on Target": A Case of an Unusual Peripheral Ossifying Fibroma of the Edentulous Upper Jaw Irritated by the Only Teeth of the Lower Jaw.

A peripheral ossifying fibroma (POF) is a benign, localized lesion that originates from the periosteum or periodontal ligament after traumatic or calculus irritation. The lesions typically manifest in females throughout their second and third decades of life. The diagnosis of a POF is challenging from both clinical and histological standpoints, as it exhibits overlapping features with numerous other clinical entities. This case describes an unusual occurrence of POFs in the anterior maxilla of a 66-year-old female patient who is edentulous at this jaw, but the last two teeth of the lower jaw affect it. The radiographic evaluation revealed no discernible alterations within the bone structure. The diagnosis of POFs was determined through histological investigation. The microscopic examination revealed scattered immature osteoid dystrophic calcified depositions in deep positions, whereas the overlying stratified squamous epithelium manifested frictional keratosis (hyperplasia). The stromal fibroblasts of the collagenous stroma displayed ovoid, normochromatic nuclei, without atypia. Interestingly, the particular importance of this POF case indicates the possibility of an atypical formation in terms of age and location suggesting the role of local chronic irritation as the most critical parameter. Regardless of the initial causative factor, which may be the remnants of the periodontal ligament, the periosteum, or the gingival fibroblasts, ultimately mechanical trauma constitutes the crucial prerequisite so that reactive hyperplasias may be induced.

Rare Case of Peripheral Myxofibroma of Anterior Maxillary Gingiva: A Diagnostic Challenge.

The myxofibroma (MF) constitutes an uncommon, non-malignant, odontogenic neoplasm with potential mesenchymal derivation. The occurrence rate of this particular tumor is estimated to be around 0.05 new cases per million individuals annually. MFs exhibit a higher incidence rate within the age range of 10 to 30 years. The prevalence of these tumors is higher among the female population, with a predominant localization in the mandible, specifically in the posterior region. A female patient, 66 years old, was referred to the Department of Oral Surgery, Surgical Implantology and Radiology, Thessaloniki, Greece, complaining of a tumorous lesion in the anterior area of the maxilla and mild pain. Clinically, a solid in palpation lobulated tumor, covered by normal coloured mucosa was observed at the left upper incisor. After the excisional biopsy, the microscopic appearance of abundant fibromyxoid stroma, in particular, myxoid stroma intermingled with collagenous tissue, covered by stratified squamous epithelium, suggested the diagnosis of peripheral myxofibroma. During a 2-year follow-up, no recurrence was referred. This case illustrates the necessity of proper differential diagnosis of every tumorous lesion of the gingiva and of using the histopathological examination.

Expression of the Embryonic Cancer Stem Cells' Biomarkers SOX2 and OCT3/4 in Oral Leukoplakias and Squamous Cell Carcinomas: A Preliminary Study.

INTRODUCTION: Cancer stem cells (CSCs) are incriminated for initiating the process of carcinogenesis either de novo or through the transformation of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of this study was to detect the expression of embryonic-type CSC markers OCT3/4 and SOX2 in OSCCs and oral leukoplakias (OLs), the most common of OPMDs. MATERIALS AND METHODS: The study type is experimental, and the study design is characterized as semiquantitative research, which belongs to the branch of experimental research. The experiment was conducted in the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. This study focuses on the semiquantitative immunohistochemical (IHC) pattern of expression of CSCs protein-biomarkers SOX2 and OCT3/4, in paraffin embedded samples of 21 OSCCs of different grades of differentiation and 30 cases of OLs with different grades of dysplasia, compared to five cases of normal oral mucosa in both terms of cells' stain positivity and intensity. Statistical analysis was performed through SPSS 2017 Pearson Chi-square and the significance level was set at 0.05 (p=0.05). The expression of the respective genes of SOX2 and OCT3/4 was studied through quantitative polymerase chain reaction (qPCR), in paraffin-embedded samples of 12 cases of OLs with mild/non dysplasia and 19 cases moderately/poorly differentiated OSCCs(n=19) and five normal mucosa using the Independent Paired T-test. RESULTS: The genes SOX2 and Oct3/4 were expressed in all examined cases although no statistically significant correlations among normal, OL and OSCC, were established. A nuclear/membrane staining of OCT3/4 was noticed only in three out of 21 OSCCs but in none of OLs or normal cases (without statistical significance). A characteristic nuclear staining of SOX2 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. SOX2 was significantly detected in the OSCCs group (strong positivity in 17/21) than in the OL group (30 cases, mostly mildly stained) (p-value=0.007), and the normal oral epithelium (mild stained, p=0.065). Furthermore, SOX2 was overexpressed in well differentiated OSCCs group (5/OSCCs, strongly stained) rather than in mildly dysplastic and non-dysplastic OLs samples (14/OLs, mildly stained) (p-value =0.035). CONCLUSION: The characteristic expression of SOX2 but not of OCT3/4 in OLs' and OSCCs' lesions suggests the presence of neoplastic cells with certain CSC characteristics whose implication in the early stages of oral tumorigenesis could be further evaluated. The clinical use of SOX2, as prognostic factor, requires further experimental evaluation in larger number of samples.

A Novel Approach to Differentiating Erosive and Reticular Lichen Planus Based on the Percentage of Dental Surfaces With Metal Restorations.

Introduction Oral lichen planus (OLP) and oral lichenoid reaction (OLR) constitute clinical entities with strong but unclear etiologic relation to dental materials. The aim of this study was to evaluate a correlation between the clinical form of OLP/OLR and the number of dental metal restorations in the oral cavity thus utilizing an exposure to metal (EM) index.  Material and methods The study type is experimental, and the study design is characterized as semiquantitative research that belongs to the branch of experimental research. Twenty-nine patients were chosen based on clinical (either reticular or erosive clinical forms) and histologic findings suggestive of OLP/OLR. The files of patients were retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, during the period 2009-2019. The medical history of the patients did not include any disorder or medication associated with lichenoid lesions and the measurements took place concurrently with the establishment of the diagnosis, thus no treatment for the lichen planus had been administered prior to the measurements. Quantitative measurement of the percentage of dental surfaces restored through metal restorations and correlation with the clinical and histologic findings of OLP/OLR was evaluated. The EM index was evaluated on a scale of 1-3, which corresponds to the percentage of dental surfaces restored through metal restorations. The statistical analysis was performed with the Pearson chi-square test and the significance level was set at p≤0.05. Results The EM index was measured by dividing each tooth into five surfaces (occlusal, mesial, distal, buccal, lingual), subsequently multiplying the number of available teeth with the number 5 to calculate the total number of surfaces, and then counting the number of surfaces with metal restorations - both fillings and crowns (in case of metal-ceramic crowns, the respective dental surface is taken into account only in case of macroscopically exposed metal), dividing the number of surfaces with metal restorations with the total number of surfaces and multiply by 100 so that the results take the form of percentages (%) and finally classifying the percentages into three groups: 1: 0% metal restorations, 2: 1-25% metal restorations, 3: >26% metal restorations). The percentage in female patients ranged from 0% to 100%, whereas it ranged from 0% to 60% in male patients. According to the clinical form of the lichenoid lesion, the percentage ranged from 0% to 60% in reticular lichen planus cases and from 0% to 100% in erosive lichen planus cases. There was no statistical difference between lichen planus cases, in total, and in normal oral epithelium. However, the levels of EM were marginally similar between the reticular lichen planus and the erosive lichen planus (Fisher's exact test, p = 0.056). Therefore, it may be the case that the EM index is higher in erosive lichenoid lesions. Conclusion In our study, the EM index was higher in female patients and in erosive lichenoid lesions. These findings should be tested and supported by larger samples of patients since the aforementioned Fisher's Exact Test, p = 0.056 could fall below the threshold of 0.05 if more patients were included. This is the first attempt to establish a novel approach to differentiating erosive and reticular lichen planus based on the percentage of dental surfaces with metal restorations.

Cancer Stem Cells' Biomarker ALDH1&2 Increased Expression in Erosive Oral Lichen Planus Compared to Oral Leukoplakia.

INTRODUCTION: ALDH1&2 has been considered an oral cancer stem cell (CSC) marker. Oral carcinogenesis is a process that usually passes through oral potentially malignant disorders (OPMD). Oral lichen planus (OLP) consists of immune-related chronic disorders that have been included in the OPMDs due to their possible transformation into oral cancer. The aim of this study was to investigate the early presence of ALDH1&2 in OLP compared to early oral leukoplakias (OL), especially mildly and non-dysplastic OL. MATERIALS AND METHODS: The study type is experimental, and the study design is characterized as semiquantitative research which belongs to the branch of experimental research. The study sample consisted of paraffin-embedded OLP biopsy samples from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, during the period 2009-2019. The study sample contained 24 cases of OLP (14 erosive and 10 reticular) and 30 cases of OL (16 cases of moderately and severely dysplastic OL and 14 cases of mildly and non-dysplastic OL). The CSC-related biomarker ALDH1&2 was examined using semiquantitative immunohistochemistry (monoclonal antibody sc-166362, Santa Cruz Biotechnology, Dallas, Texas, USA, 1:100). ALDH1&2 expression was evaluated through a scale of 1 to 3 depending on the percentage of positive epithelial cells and was compared to normal epithelium as well as cases of OL (the most prominent OPMD). The statistical analysis was performed with the Pearson chi-square test and the significance level was set at p≤0.05. RESULTS: The cytoplasmic staining of ALDH1&2 was observed mostly in the epithelial cells of the basal layer of the epithelium of OLP. Overall, this expression was significantly increased compared to normal epithelium. In addition, statistically significantly higher expression of ALDH1&2 was observed in the erosive form of OLP. Interestingly, this OLP positivity was higher compared to mild and non-dysplastic leukoplakias (p<0.001). CONCLUSIONS: ALDH1&2 is a confirmed CSC marker that was found to be clearly increased in OLP and characteristically in erosive OLP epithelium for the first time. Noteworthy, it was more prominent in erosive OLP rather than in mildly and non-dysplastic OL. Whether this pattern of expression raises the red flag of an early epithelial "CSC" phenotype in OLP or that ALDH1&2 expression indicates a response to the OLP inflammatory process requires further investigation.

Immunohistochemical Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Salivary Gland Cancer: Correlation with the Biological Behavior.

Salivary gland neoplasms comprise a diverse group of tumors with different biological behaviors and clinical outcomes. Understanding the underlying molecular alterations associated with these malignancies is critical for accurate diagnosis, prognosis, and treatment strategies. Among the many biomarkers under investigation, epithelial cell adhesion molecule (EpCAM) has emerged as a promising candidate in salivary gland cancer research. This article aims to provide a comprehensive overview of the differential expression of EpCAM in salivary gland cancer and its potential correlation with the biological behavior of these tumors. The clinical characteristics of 65 patients with salivary gland malignancy of different histopathological subtypes were included. We report the differential expression of EpCAM and the relationship between the clinical and histopathologic features of these tumors. Regarding the evaluation of the effect of EpCAM expression on survival, in our study, we showed that tumors with high EpCAM expression had reduced disease-free survival (DFS) and overall survival (OS) (p < 0.001) compared to patients with cancers with low EpCAM expression. In addition, the concurrent presence of perineural invasion and positive EpCAM expression appeared to be associated with shorter disease-free survival and overall survival. In conclusion, our study confirmed the prognostic value of detecting perineural invasion and EpCAM expression.

Cyclosporine-Induced Gingival Hyperplasia in a Patient With Lichen Planopilaris: Misfortunes Never Come Singly!

Cyclosporine A constitutes an immunosuppressive medication administered against various autoimmune and autoinflammatory disorders as well as against graft versus host disease. Its most well-known oral adverse effect is gingival hyperplasia. The aim of this study is to report a persistent case of a patient with lichen planopilaris with alopecia treated with cyclosporine leading to the manifestation of gingival hypertrophy. A female patient aged 38 years old was referred to the Department of Oral Medicine/Pathology, Dental School, Aristotle University of Thessaloniki, Greece complaining about gum bleeding, halitosis, and a persistent gingival enlargement, which appeared two months ago. According to her medical history, lichen planopilaris was diagnosed six months ago and was initially treated for 40 days with methylprednisolone 16 mg twice per day without improvement, and was replaced by cyclosporine A 200 mg per day. The clinical oral examination revealed gingival enlargement at areas #34-43, 22-23, and 25-27 without any lesion of lichen planus. The level of oral hygiene was satisfactory, with a limited amount of tartar and plaque. Bleeding on probing was also noticed, and pseudopockets of 5 mm were observed. The serum levels of cyclosporine were 473,60 µg/L, with a normal range, regarding repercussions in the oral cavity, up to 200 µg/L. A decrease of cyclosporine dosage to 150 mg was performed. After 15 days, the clinical appearance significantly improved, and a biopsy was done. The microscopic findings showed mild ulceration and inflammatory infiltrates, together with the abundant presence of collagen stroma, without any sign of malignancy. According to the literature, the high dosage of cyclosporine, its relevant high serum levels, and the presence of plaque were responsible for the manifestation of gingival hypertrophy.

Aldehyde Dehydrogenase: An Off-Label Marker of Endothelial Activation in Oral Squamous Cell Carcinoma.

INTRODUCTION: The vascular endothelial (VE) expression of aldehyde dehydrogenase (ALDH) 1/2 family in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cases has not been studied so far. The aim of this study was to illustrate the "off-label" endothelial expression of cancer stem cell (CSC) biomarker, ALDH1/2, adjacent to oral potentially malignant and malignant lesions in order to shed some light on the mechanisms leading to oral carcinogenesis.  Materials and methods: The expression of CSC protein-biomarker ALDH1/2 was detected through immunohistochemistry (IHC) in 30 paraffin-embedded samples of OL and 21 samples of OSCC compared to five samples of normal oral mucosa. Statistical analysis was done using SPSS, Pearson Chi-square, and Fischer's exact test. The significance level was set at 0.05 (p≤ 0.05).  Results: In oral mucosal vessels, ALDH1/2 was not expressed. It was expressed significantly more in the vessels of OSCCs compared to the OLs (Fisher's exact test, p-value= 0,001). However, when endothelial expression of ALDH1/2 in the vasculature of OLs was compared with that of the normal oral mucosa, no significant change was noticed (Fisher's exact test, p-value=1.000).  Discussion: The IHC VE expression of ALDH1/2 in OSCC vasculature but not in OL indicates a possible significantly stronger activation of endothelial cells during carcinogenesis, which could be an indicator of the role of inflammation in the development of field cancerization and of prognostic value for (vascular/lymphatic) metastasis.

Oral Squamous Cell Carcinoma (OSCC) Imitates Denosumab-Induced Osteonecrosis of the Mandibular Alveolus: A Diagnostic Challenge.

Oral squamous cell carcinoma (OSCC) may arise in the the alveolar ridge (in a minority of cases). Smoking, chronic mucosal injuries, and poor oral hygiene are involved in its pathogenesis. It mostly occurs to men instead of women and affects the mandible on a 3:2 ratio to the maxilla. The objective of the current study is to present an interesting case of an OSCC of the alveolar ridge mimicking jaw osteonecrosis due to denosumab, resulting in differential diagnostic dilemmas. A 78-year-old female patient, edentulous and bearing total dentures, was referred with a persistent (four months), severely painful, ulcerative lesion in the anterior lateral (right) region of the residual alveolar ridge of the mandible. Medical history referred to a long-term systemic steroid use due to sarcoidosis as well as the subcutaneous use of denosumab for osteoporosis one/month for one year. Cone-beam CT (CBCT) examination was performed where bone resorption was detected and a differential diagnosis of osteonecrosis of the jaws (ONJs) from denosumab or neoplasia was made. A biopsy was carried out, and the histological examination showed that soft tissues and underlying bone were infiltrated by abnormal, confluent, compact islands of malignant squamous cells with intense atypia and numerous mitoses indicating a moderately differentiated OSCC. Denosumab inhibits the binding of receptor activator of nuclear factor ligand (RANKL) to receptor activator of nuclear factor-kappa (RANK); this decreases bone resorption and results in increased bone density. However, denosumab may induce ONJ. The area of exposed bone and abnormal soft tissue alterations may resemble both benign and malignant diseases. Osteonecrosis may mimic OSCC or may even provide the suitable substrate for the development of OSCC. Biopsy as well as bone imaging examination are required to accurately determine the possibility of neoplastic formation and its boundaries in cases of osteonecrosis especially in patients under treatment with denosumab or bisphosphonate-related ONJ (BRONJ).

Alport Syndrome and Oral Mucous Membrane Pemphigoid: An Interesting Case.

Alport syndrome (AS) is a hereditary progressive glomerular disease associated with sensorineural hearing loss and ocular abnormalities. It is attributed to the altered structure and the subsequent dysfunction of the glomerular basement membrane (GBM) due to the mutated type IV collagen a3/a4/a5 chains. It may emerge either as an X-linked disease, the most common, or as an autosomal disease, both recessive and dominant. A female patient, 26 years old, came in 2023 to the Department of Oral Medicine/ Pathology, Dental School, Aristotle University of Thessaloniki, complaining about pain and a burning sensation in her right cheek. Her medical history revealed the diagnosis of Alport syndrome in 2016 and kidney transplantation in 2022 with extensive post-transplantation drug administration. The clinical examination revealed an ulcer, partially covered by a pseudomembrane, on the oral mucosa of the right cheek, surrounded by an erythematous border. A biopsy was taken, and the histopathological examination showed the oral manifestation of mucous membrane pemphigoid. After communicating with the attending nephrologist, the prescription of methylprednisolone was decided, and the lesions receded. The differential diagnosis included both AS-induced pemphigoid and drug-induced pemphigoid. The thorough medical history, detailed clinical investigation, lesion biopsy, and collaboration of different dental and medical specialties constitute necessary prerequisites for a successful treatment, even in immunosuppressed patients.

Preliminary Study of the Cancer Stem Cells' Biomarker CD147 in Leukoplakia: Dysplasia and Squamous Cell Carcinoma of Oral Epithelial Origin.

Objectives Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis de novo, as well as through the transformation of oral potential malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of our study was to detect the expression of stemness-type CSC marker CD147 in oral leukoplakias (OLs), the most common OPMD, and OSCCs as well. Materials and methods This study focuses on the semiquantitative immunohistochemical pattern of the expression of the CSC protein biomarker CD147 in paraffin-embedded samples of 20 OSCCs of different grades of differentiation and 30 cases of OLs without or with different grades of dysplasia, compared to the normal oral epithelium in terms of cells' stain positivity. Statistical analysis was performed through Statistical Package for Social Sciences (SPSS) version 25.0 (IBM SPSS Statistics, Armonk, NY) with Pearson chi-square test, and the significance level was set at 0.05 (p=0.05). In addition, the study clarified the expression of the respective gene of CD147 through quantitative polymerase chain (qPCR), in paraffin-embedded samples of the two extreme graduations: OLs of mildly dysplastic or non-dysplastic cases (n=10 cases) and OSCCs of moderately/poorly differentiated cases (n=17). Statistical analysis was then performed through SPSS version 25.0 with an independent paired t-test, and the significance level was set at 0.05 (p=0.05). Results The gene CD147 was expressed in all cases, although no statistically significant correlations were established. Regarding its protein products, the characteristic membranous staining of CD147 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. CD147 was upregulated significantly in the moderately and severely dysplastic OLs than in the mildly dysplastic and non-dysplastic OLs (p=0.008). Also, CD147 was upregulated significantly in the mildly dysplastic and non-dysplastic OLs than in the normal oral epithelium (p=0.012). Discussion The characteristic expression of CD147 in OLs and OSCCs' lesions suggests the presence of stemlike cancer cells, illustrating an underlying effect on the early stages of oral dysplasia, in the OL stage. The clinical application of CD147 as prognostic factor requires the experimental evaluation in larger number of samples. Conclusion Stem cells play an important role in the process of carcinogenesis. A major goal in cancer research is the identification of specific biomarkers for the detection of cancer stem cells. CD147 is considered as an innovative stem cell marker. Our findings in oral mucosal potentially malignant disorders showed that CD147 is expressed more intensely in parallel with the progression of the grade of dysplasia in OL. On the other hand, in oral squamous cell carcinoma, CD147 expression remains stable regardless of the degree of differentiation.

Minor salivary gland stem cells: a comparative study of the biological properties under clinical-grade culture conditions.

Development of clinical-grade, cell preparations is central to cGMP (good manufacturing practice compliant) conditions. This study aimed to investigate the potential of two serum/xeno-free, cGMP (StemPro, StemMacs) culture media to maintain "stemness" of human minor salivary gland stem cell (mSG-SC) cultures compared to a complete culture medium (CCM). Overall, StemMacs resulted in higher proliferation rates after p.6 compared to the conventional serum-based medium, while StemPro showed substantial delays in cell proliferation after p.9. The mSG-SCs cultures exhibited two distinct cell populations at early passages a mesenchymal subpopulation and an epithelial-like subpopulation. Expression of several markers (CD146, STRO-1, SSEA-4, CD105, CD106, CD34, K 7/8, K14, K18) variably decreased with prolonged passaging (all three media). The percentage of SA-ß-gal positive cells was initially higher for StemMacs compared to StemPro/CCM and increased with prolonged passaging in all cases. The telomere fragment length decreased with prolonged passaging in all three media but more pronouncedly for the CCM. Expansion under serum-free conditions caused pronounced upregulation of ALP and BMP-2, with parallel complete elimination of the baseline expressions of LPL (all three media) and ACAN (serum-free media), therefore, showing a preferential shift of the mSG-SCs towards osteogenic phenotypes. Finally, several markers (Nanog, SOX-2, PDX-1, OTX2, GSC, HCG) decreased with prolonged culture, indicating successive loss of "stemness". Based on the findings, it seems that StemPro preserve stemness of the mSG-SCs after prolonged culture. Nevertheless, there is still a vacant role for the ideal development of clinical-grade culture conditions.

A Differential Clinical Diagnostic Challenge of a Recurrent, Oral Fibrosarcoma Resembling a Periapical Lesion of Endodontic Origin.

A fibrosarcoma is a neoplastic growth originating from malignant, fibroblast-like mesenchymal cells. This malignant tumor shows an increased tendency for expansion and recurrence and a propensity to metastasize, especially to the lungs. Despite their rarity, fibrosarcomas have the potential to manifest in any anatomical location. An oncologist referred their patient due to reported mandibular discomfort, ache, and swelling. The biopsy revealed a fibrosarcoma resembling a periapical lesion of endodontic origin. The timely intervention and the collaboration among different but complementary medical and dental specialties ensure that the patient may enjoy a prolonged life expectancy as symptom-free as possible.

A Case Report of Ibandronic Acid Induced Non-Exposed BRONJ Involving the Maxillary Sinus.

Background: The aim of this case report is to present an interesting case of bisphosphonate-related osteonecrosis of the jaw, involving the maxilla and the maxillary sinus, as a result of per os administration of ibandronic acid. Methods: A female patient, 62 years old, was referred to the Department of Dentoalveolar Surgery, Surgical Implantology and Radiology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining about pain in the first quadrant. Her medical history revealed per os bisphosphonate administration for the past four years. Subsequently, the cone-beam computed tomography examination revealed a small sequestrum of bone, surrounded by radiolucency, in proximity with the sinus floor. The clinical examination didn't reveal any pathological clinical signs. Results: Based on the radiological examination, a surgical approach was implemented to remove the necrotic bone, irrigate the alveolar process and the sinus with saline, and finally achieve primary closure, after which, the patient healed uneventfully. The osteonecrosis was attributed to the bisphosphonate administration. Conclusions: Bisphosphonate-related osteonecrosis of the jaw without obvious or with minor implication of gingival tissues is a diagnostic challenge indicating an early stage of this adverse reaction. Imaging is critical for the early detection of those cases. After careful choice of the case the proper surgical intervention could be effective to eliminate a future advancement of bone destruction. The prevention of osteonecrosis of the jaw can be achieved through the provision of adequate education to dental medicine practitioners, medical doctors, and patients.

Ultrasonographic Diagnosis of Osteochondroma of the Mandible: A Case Report.

Aim of the study: The aim of the present paper is to determine the diagnostic features of the rare presentation of osteochondroma in the mandible. The unusual aspect in this case is that the diagnosis was not established with cone beam computer tomography, which is a commonly used radiographic technique in dentistry, but with the use of ultrasonography. Case description: Ultrasonography is very useful for initial examinations, avoiding patient exposure to additional radiation and setting the diagnosis in debatable soft tissue involvement of various lesions. In the presented case, even though the clinical presentation was indicative, the cone beam computer tomography evaluation could not confirm the diagnosis, so the final diagnosis was made by ultrasonography. Conclusions: With the latest advances in the applications of ultrasonography in the maxillofacial region, an examination of lesions on the floor of the mouth or in the neck area may set the diagnosis in cases where hard tissue imaging does not provide enough information.

IL-10 and TGF-beta1 gene polymorphismsin Greek patients with recurrent aphthous stomatitis

Background: Recurrent aphthous stomatitis (RAS) is one of the most frequent inflammatory disorders of theoral mucosa. Cytokines, which play an important role in RAS pathogenesis, participate directly or indirectly innormal, immunological and inflammatory processes and are secreted from cells belonging to innate and adaptiveimmunity as a consequence of microbial and antigenic stimuli. Gene polymorphisms in specific cytokines maypredispose to RAS development. The aim of this study was the investigation and association of IL-10 and TGF-β1gene polymorphisms with RAS.Material and Methods: Study’s cohort consisted of 60 Greek patients diagnosed with RAS, including 40 patientswith minor, 10 patients with major and 10 with herpetiform aphthous ulcers. Forty age- and sex-matched controlsubjects were included in this study. DNA was extracted from whole blood samples of all patients and sequencespecific primers (SSP)-based polymerase chain reaction (PCR) was used for genotyping. Gene polymorphisms forcytokines IL-10 at loci -592 and -819 and for TGF-β1 at codon 10 were detected.Results: Significant differences between patients with minor RAS and healthy controls were recorded for IL-10genotypes distribution at position -592 (p=0.042) and -819 (p=0.045) with predominance of C/A and C/T genotypes in RAS patients, respectively. Also, in patients with minor and herpetiform aphthous ulcerations, heterozygousTGF-β1 genotype C/T at codon 10 was associated with increased risk of RAS (p=0.044 and p=0.020, respectively).Conclusions: These data provide evidence that genetic predisposition for RAS and possibly its specific clinical variants is related with the presence of gene polymorphisms for specific cytokines, including IL-10 and TGF-β1, which,in turn, may vary according to geographic origin and genetic background. (AU)

Primary Sjögren's Syndrome Presenting with Rapidly Progressive Dementia: A Case Report.

BACKGROUND: Rapidly progressive dementias (RPDs) are dementias that progress subacutely over a time period of weeks to months. Primary Sjögren's syndrome (pSS) is an autoimmune disease that can affect any organ system and may present with a wide range of clinical features that may mimic a plethora of medical conditions and, in rare cases, may manifest as RPD. We describe a unique case of pSS, in which rapidly progressive dementia (RPD) was the first disease manifestation, and the patient's radiological and electroencephalogram findings were compatible with Creutzfeldt- Jakob disease (CJD). CASE PRESENTATION: Here, we report a 58-year-old woman who presented with cognitive impairment rapidly deteriorating over the last 6 months prior to admission. Brain MRI and EEG were indicative of CJD. However, CSF 14-3-3 and tau/phospho tau ratio were within normal limits and therefore alternative diagnoses were considered. Blood tests were significant for positive antinuclear antibodies, anti-ENA, and anti-SSA and a lip biopsy was consistent with pSS. The patient was started on intravenous steroids followed by oral prednisone taper, which prevented further deterioration. CONCLUSION: This rare case expands the spectrum of neurological manifestations in pSS and highlights the importance of considering pSS in the differential diagnosis of RPDs in order to avoid misdiagnosis and provide appropriate treatment in a timely fashion.

A Review on Xerostomia and Its Various Management Strategies: The Role of Advanced Polymeric Materials in the Treatment Approaches.

The medical term xerostomia refers to the subjective sensation of oral dryness. The etiology seems to be multifactorial with the most frequently reported causes being the use of xerostomic medications, neck and head radiation, and systematic diseases (such as Sjögren's syndrome). Xerostomia is associated with an increased incidence of dental caries, oral fungal infections, and difficulties in speaking and chewing/swallowing, which ultimately affect the oral health-related quality of life. The development of successful management schemes is regarded as a highly challenging project due to the complexity of saliva. This is why, in spite of the fact that there are therapeutic options aiming to improve salivary function, most management approaches are alleviation-oriented. In any case, polymers are an integral part of the various formulations used in every current treatment approach, especially in the saliva substitutes, due to their function as thickening and lubricating agents or, in the case of mucoadhesive polymers, their ability to prolong the treatment effect. In this context, the present review aims to scrutinize the literature and presents an overview of the role of various polymers (or copolymers) on either already commercially available formulations or novel drug delivery systems currently under research and development.