Immune-mediated oral mucosal pathology: a comprehensive review and update for clinicians - part II.

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort, and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlap in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover recurrent aphthous stomatitis, pemphigus vulgaris and mucous membrane pemphigoid, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

Multidisciplinary Therapeutic Approach of a Patient With Sjogren's Syndrome: A Three-Year Follow-Up Study.

Sjögren's syndrome is a chronic, inflammatory autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands. Notably, the rehabilitation of partially edentulous patients with Sjögren's syndrome is limited by the scarce availability of studies that could inform therapeutic modalities and potential challenges during clinical procedures. This case report aimed to present the oral rehabilitation of a patient with Sjögren's syndrome who received fixed partial dentures (FPDs). A 28-year-old female patient sought treatment to restore her missing teeth. She was diagnosed with Sjögren's syndrome by a rheumatologist adhering to the revised version of the European criteria proposed by the American-European Consensus Group and was on a medication regimen including prednisolone, hydroxychloroquine, pantoprazole, pilocarpine, and tear substitutes to manage her condition. The final treatment plan consisted of extractions, management of gingivitis, post-and-core restorations, and a 2 mm vertical dimension increase with the placement of 15 porcelain-fused-to-metal (PFM) crowns and 4 short-span bridges. The patient underwent regular clinical and radiographic evaluations every 3 months since June 2020. Throughout this period, the fixed prostheses, teeth, and periodontal tissues demonstrated remarkable stability and exhibited no complications. This three-year case study provides evidence that meticulous planning and clinical execution can facilitate successful oral rehabilitation in young edentulous patients with Sjögren's syndrome. Tooth-supported fixed prostheses can effectively restore oral function and aesthetic appeal in these individuals, provided they undergo more frequent dental examinations than the general population and maintain a cooperative attitude throughout the treatment process.

Citalopram-Induced Oral Melanotic Macules in a Female Patient and a Review of the Literature.

Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology can be categorized as physiologic, reactive, neoplastic, idiopathic, or indicative of systemic illness. Several systemic drugs have been linked to the development of oral and/or cutaneous pigmentation, either by stimulating the production of melanin or by the accumulation of the drug or its byproducts. The medications most commonly associated with this condition include antimalarials, hormones, oral contraceptives, phenothiazines, chemotherapeutics, amiodarone, minocycline, zidovudine, clofazimine, and ketoconazole. The aim of this case report is to illustrate the drug-induced appearance of multiple melanotic macules in an 89-year-old female patient. The patient was referred to the Department of Oral Medicine and Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining of the recent and constant appearance of black spots in her oral cavity. Her medical history revealed a multitude of prescribed drugs, with citalopram being the most recently prescribed one, approximately one year prior to the examination. The clinical examination revealed multiple melanotic macules, on the upper and lower lip as well as on the hard and soft palate. Based on these findings, a biopsy of a melanotic macule of the lip was carried out. The histopathological examination showed that the basal layer of the stratified squamous epithelium exhibited hyperpigmentation (melanin-pigmented basal cells). In addition, scattered melaninophages were noted in lamina propria. Psychotropic drugs associated with cutaneous hyperpigmentation include citalopram. Therefore, our case constitutes an exception since citalopram induced intraoral and perioral, instead of cutaneous, hyperpigmentation.

An Unusual Case of Psoriatic Arthritis With Secondary Lingual Lesions, Resembling Geographic Tongue.

Psoriatic arthritis (PsA) is a chronic inflammatory condition that impacts a significant proportion of individuals diagnosed with psoriasis. This report presents a rare case of a patient diagnosed with PsA who never had active psoriatic skin lesions but only a family history of psoriasis, with secondary lingual lesions, resembling geographic tongue (GT). A male patient, 24 years old, was referred with two painless erythematous areas resembling (without whitish borders, as in GT) rounded atrophic lesions on the dorsal surface of the tongue, resistant to any kind of antimicrobial/antifungal treatment for more than six months. The patient was diagnosed with PsA two years ago fulfilling the CASPAR (ClASsification for Psoriatic ARthritis) criteria. The patient never had active psoriatic skin lesions, but his father had psoriasis. The biopsy of lingual lesions showed moderate hyperkeratosis, spongiosis, and diffuse inflammatory infiltration of lymphocytes and neutrophils in the lamina propria as well as in the stratified squamous epithelium forming Munro's microabscesses at the superficial layers. The manifestation of the atypical psoriasiform, GT-like lingual lesions was considered as part of psoriasis manifestations and the patient was advised to follow regular checkups so that any major exacerbation of the systematic symptoms could be preemptively avoided. Not only GT but also atypical lingual GT-like reddish oral lesions may be considered as transient forms of psoriasis supporting an early diagnosis and monitoring of psoriasis/PsA.

The Occurrence of Etoricoxib-Induced Stevens-Johnson Syndrome With Oral Manifestations in a Female Patient: A Case Study.

Stevens-Johnson Syndrome (SJS) constitutes a rather uncommon, and rarely fatal hypersensitivity reaction that primarily impacts the skin and mucous membranes and in certain cases may be attributed to drug administration. The aim of this article is to present a case of etoricoxib-induced SJS in a 46-year-old, female patient. The patient presented herself, as a medical emergency, to the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, reporting pain, especially acute pain while eating certain foods, discomfort, dysphagia, and a wound in the left half of the hard palate. The clinical examination revealed a broad ulcer, in the left half of the hard palate as well as multiple ulcerations and erosions in the upper and lower lip. Her medical history was clear; however, the patient mentioned to have received etoricoxib, due to severe back pain, one day prior to our clinical examination. The patient received methylprednisolone 16 mg, twice per day, for two days, followed by methylprednisolone 8 mg, twice per day, for two more days. Her symptoms resigned and since the connection between etoricoxib and SJS was established, the patient was advised to avoid etoricoxib and be wary of adverse effects, when taking drugs especially non-steroidal anti-inflammatory medication. This is one of the first case reports in the literature, linking etoricoxib administration with the emergence of SJS, highlighting the importance of pharmacovigilance. The up-to-date registration of drug-induced adverse effects is of immense importance to protect future patients. SJS does not have a defined treatment strategy. Therefore, most patients are given supportive care and symptomatic treatment, which most commonly involves corticosteroids and antivirals such as acyclovir.

Investigation of the Vascular-Endothelial Pattern of Expression of DAPK-1 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders Through Immunohistochemistry.

Introduction Potentially malignant disorders, like oral lichen planus (OLP) and oral leukoplakia (OL) of several degrees of dysplasia, manifest a significant potential of malignant transformation being a precursor of oral squamous cell carcinoma (OSCC). The role of microvascularization in carcinogenesis is critical; therefore, microvascularization constitutes a major therapeutic target. DAPK-1 constitutes a possible cancer marker, with proven implications in other human cancers, and there isn't any study on its vascular endothelial expression in the oral cavity, particularly in oral cancer and oral potentially malignant diseases. The present study aims to investigate the vascular endothelial expression of the DAPK-1 in paraffin-embedded tissue samples of oral leukoplakia, oral squamous cell carcinoma, and oral lichen planus. Materials and methods The study focuses on the immunohistochemical, vascular-endothelial, expression pattern of biomarker DAPK-1 (NBP2-38468, Novus Biologicals, Centennial, CO, US). Tissue samples were obtained from six cases of oral lichen planus (OLP) (3 of reticular and 3 of erosive form), 30 cases of oral leukoplakia (OL) (10 with no dysplasia, 10 with mild dysplasia, and 10 with moderate/severe dysplasia), 22 cases of OSCC (2 well-differentiated, 17 moderately differentiated, and 3 poorly differentiated), as well as 5 cases of normal oral epithelium. The tissue samples were retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, as well as from St Lukas Hospital of Thessaloniki, Greece, from 2004-2019. In accordance with the Research and Ethics Committee guidelines of the Aristotle University, School of Dentistry, and the Helsinki II declaration, the study was conducted. The primary inclusion criteria for the study focused on the presence of sufficient precancerous or cancerous tissue. Conversely, inadequate tissue served as the exclusion criteria. The staining was evaluated exclusively in a quantitative manner. The vascular endothelial staining was evaluated as either positive or negative. If at least one endothelial cell exhibited positive staining, the section was classified as positive. Statistical analysis was carried out using SPSS Statistics v25.0 (IBM Corp., Armonk, NY, US) utilizing Pearson's chi-square or Fisher's exact test, depending on the sample size, to compare OLP to OL, OLP to OSCC, OLP to normal, OL to OSCC, OL to normal, and OSCC to normal. The significance level was established at 0.05 (p=0.05). Results A prevalence of positive OL cases may be noticed. The comparison between OLP and OL yielded Fisher's exact test of p>0.999, OLP and OSCC p=0.389, OLP and normal oral epithelium p>0.999, OL and OSCC p=0.226, OL and normal oral epithelium p>0.999, as well as OSCC and normal oral epithelium p=0.342. Conclusions The role of DAPK in tumorigenesis is already supported by limited literature. However, its implication in the development of OSCC and oral potentially malignant disorders (OPMDs) has yet to be elucidated. Its elevated expression in OL suggests a role in affecting the microenvironment, the vessels, in particular, surrounding oral potentially malignant lesions, possibly assisting their transition into cancer. The evaluation of the vascular-endothelial immunohistochemical profile of DAPK-1 in OL, OLP, and OSCC requires further studies in more tissue samples to illustrate its possible implications.

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.

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).

Altered Presence of Cancer Stem Cell ALDH1/2 in Oral Leukoplakias and Squamous Cell Carcinomas.

INTRODUCTION: Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis by enabling the self-renewal and self-proliferation of the cancer cells. This study aimed to investigate the presence of epithelial cells with cancer stem cells characteristics (ALDH+) in the early stages of oral precancerous lesions (Oral Leukoplakias) and the frequency of these cells in the different stages of oral squamous cell carcinomas (OSCCs). MATERIALS & METHODS: The aim of this study was the detection of the immunohistochemical pattern of expression of CSC protein-biomarker ALDH1&2 (sc-166362, Santa Cruz Co, Dallas, Texas, USA) in paraffin-embedded samples of 30 cases of leukoplakia of all degrees of dysplasia and 21 cases of oral squamous cell carcinomas (OSCC) of all degrees of differentiation compared to the histologically normal oral epithelium. The samples were retrieved from 2009-2019 from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. The samples were evaluated through a three-tier scale (positive cells Ι: 6-35%, ΙΙ: 36-70%, ΙΙΙ: 71-100%). Statistical analysis was performed through SPSS Pearson Chi-square, and the significance level was set at 0.05 (p=0.05).  Results: The staining of ALDH1&2 was observed mildly in the cell membrane of cells in the stratum spinosum of the normal epithelium and the cell membrane of cells in the stratum basale of the normal epithelium, characteristically at the interface point with the basal membrane. ALDH1&2 were expressed significantly more in the OSCC than in the leukoplakia (p-value=0.0001) and the normal epithelium (p-value=0.0001). Mainly, ALDH1&2 were expressed significantly more in the severely and moderately dysplastic oral leukoplakia compared to the mildly dysplastic and non-dysplastic leukoplakia (p-value=0.001). DISCUSSION: The characteristic expression of ALDH in potentially malignant oral and OSCC lesions suggests the presence of CSCs and their possible implication in the early stages of oral tumorigenesis, even at the stage of oral leukoplakia.

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.

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.

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.

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.

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.

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.

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.

"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.

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.