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Background: Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells that generally affects children; LCH onset is rare in adults; immunohistochemistry is essential to obtain the correct diagnosis, and treatment protocols are controversial. Objective: To describe two new cases of adult onset oral LCH. Case reports: Case 1: a 71-year-old woman, complaining of diffuse oral pain, presented with erythematous mucosal lesions; the panoramic radiograph and CT scan showed multiple mandible radiolucent areas. Immunohistochemical assay for S-100, CD1a and langerin test was essential in reaching the correct diagnosis. Case 2: a 77-year-old female patient presented with a non-painful, non-bleeding, slightly elevated erythematous palatal lesion of 6 months duration, together with a genital vulvar lesion of uncertain nature. The pathology confirmed the diagnosis of LCH. Many therapies (etoposid, radiotherapy) could induce only a clinical partial remission; Cladribine induced a complete recovery. Conclusion: The first case was difficult to diagnose: the clinical presentation and course of the disease (LCH) in the elderly are multiple and unpredictable. An immunohistochemistry study is often essential to obtain the correct diagnosis. The second case required several therapeutic interventions: even though some cases regress spontaneously, others require systemic chemotherapy.

Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed. Major aims of this review are to update the understanding of HPV activities with respect to oral oncology and to comment on the HPV DNA reported frequencies in OSCC and potentially malignant oral lesions. A computer database search was performed, through the use of MEDLINE (PubMED) and Cochrane Library, for the last three decades. Search key words used were: human papillomavirus, HPV and cancer, HPV and oral lesions, HPV and oral premalignant lesions, HPV and oral cancer, HPV and HNSCC, HPV and oral mucosa. The search was of all fields, all languages and all dates available.

Photodynamic Therapy (PDT) is a minimally invasive approach that has shown promising results in management of oral, head and neck lesions. PDT can be used alone or in combination with other conventional treatments (surgery, chemotherapy, radiotherapy). Oral Lichen Planus (OLP) is a mucosal and cutaneous chronic disease characterized by an autoimmune insult of basal keratinocytes. We aim to evaluate the feasibility of topical toluidine blue-mediated PDT for the treatment of oral cavity multifocal homogeneous white lesions by oral lichen planus without dysplastic features.

Calcium glucarate (CGT) is a promising chemopreventive agent. This study evaluated the in vivo efficacy of CGT in preventing 7,12-dimethylbenz(alpha) anthracene (DMBA)-induced oral carcinogenesis in the hamster. Matherials and Methods: Seventy-six Syrian hamsters were used, divided into four groups: group 1, untreated animals; 2, CGT controls; 3, DMBA-treated; 4, DMBA- and CGT-treated. Hamsters were painted three times weekly with 0.5% solution of DMBA and were fed a diet supplemented with CGT (64 mmol/kg, 2%). Animals were sacrificed at week 9 and 12 and pathology and histomorphometric analyses were performed.At week 9, four dysplastic lesions and six carcinomas were identified in group 3 while only three dysplasias and five carcinomas were detected in group 4. At week 12, five animals of group 3 displayed a dysplasia, which was only detected in one animal of group 4. Squamous carcinomas were identified in all animals of both group 3 and 4. However, in group 3 four of the animals displayed multifocal lesions and carcinomas displayed histological features indicative of increased aggressiveness.The results obtained suggest that CGT can exert an inhibitory effect on oral carcinogenesis in tha hamster and that further studies are warranted to evaluate its potential use as a chemopreventive agent in humans.

In recent years metagenomic analysis has become more accessible for the characterization of biological specimens. There has been an important increase of studies using this technique for subgingival human samples. To date, there are no updated systematic reviews on the relationship between oral microbiota and periodontal disease. The aim of the present systematic review was to update data about studies concerning the influences of changes in oral microbiota composition on the periodontal status in human subjects.An electronic search was conducted in four databases (MEDLINE, Scopus, CENTRAL and Web of Science) for articles published in English from January 2014 to April 2018. In vitro or animal studies, case reports, case series, retrospective studies, review articles, abstracts and discussions were excluded. Also, studies that evaluated less than 5 microbial species, only viruses or already known periodontal pathogens were excluded. Two independent researches selected the studies and extracted the data. The quality of evidence was assessed as high, moderate or low for each microorganism.Eight studies and three additional publications recovered from the bibliography search of the selected articles were included in the review. The Bacteria domain was the main detected among the others and it included 53 species. The review confirmed the presence of recognized periodontal pathogens such as the members of the red complex but also identified, with high weight of evidence, the presence of new pathogens.The results of this systematic review support high evidence for the association of 3 new species/genera with the etiology of periodontitis. Future investigations on the actual role of these new pathogens in the onset and progression of the disease are needed.

Background: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. Methods: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. Results: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values5) in K-OLPs and nK-OLPs, respectively. The PSQI’s validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. Conclusions: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Background The introduction of photodynamic therapy (PDT) in various branches of the dental field such as endodontics, implantology, periodontology, and restorative dentistry and oral medicine has become useful in recent decades. This systematic review presents an overview of the literature to evaluate the usefulness of topical PDT for the treatment of benign oral soft tissue lesions and to identify limitations in prior studies to improve PDT applications. Methods We performed a review of the literature using different search engines (PubMed, ISI Web of Science, and the Cochrane Library) employing MeSH terms such as "Photodynamic therapy" and "PDT" in conjunction with other terms. We utilized the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) method to define our study eligibility criteria. Results Initial results were 1513. Finally, there were only 21 studies that met our selection criteria. We divided the 21 selected items into two groups: inflammatory diseases and infective diseases. Conclusions Although topical PDT is an easy to perform and well-tolerated treatment and appears to be a valid method with promising results in the treatment of benign lesions of the oral cavity's soft tissues, further studies are needed to complete the current knowledge of this technique.

Objective: Aims of this study were to test the efficacy of anti-BP180-NC160 ELISA in the diagnosis of oral pemphigoid compared to the gold standard, represented by direct immunofluorescence and pathological examination, to correlate the antibody titers with the severity of the disease and the demographical data. Materials and Methods: Patients with a suspect of oral pemphigoid were enrolled and underwent biopsy and sera collection both, in order to perform histopathological examination, direct immunofluorescence and ELISA. The test outcomes were compared, and ELISA sensitivity, specificity, accuracy, and negative and positive predictive values were calculated. Results: ELISA showed good specificity (83.3%), while sensitivity was only 50%. A moderate correlation between antibody titers and disease severity was recorded. Conclusions: Mucomembranous Pemphigoid is an autoimmune autoantibody-mediated blistering disease, often affecting exclusively the oral mucosa. Currently, the biopsy is required to diagnose this disease, but serological tests are also commonly employed during clinical practice as adjunctive tools. BP180-NC160 ELISA should be considered an ancillary diagnostic test in course of oral pemphigoid; direct immunofluorescence+histologic examination remains the diagnostic gold standard.

Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway. Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway.

Pseudolesions are defined as physiological or paraphysiological changes of the oral normal anatomy that can easily be misdiagnosed for pathological conditions such as potentially malignant lesions, infective and immune diseases, or neoplasms. Pseudolesions do not require treatment and a surgical or pharmacological approach can constitute an overtreatment indeed. This review aims to describe the most common pseudolesions of oral soft tissues, their possible differential diagnosis and eventual related systemic diseases or syndromes. The pseudolesions frequently observed in clinical practice and reported in literature include Fordyce granules, leukoedema, geographic tongue, fissured tongue, sublingual varices, lingual fimbriae, vallate papillae, white and black hairy tongue, Steno's duct hypertrophy, lingual tonsil, white sponge nevus, racial gingival pigmentation, lingual thyroid, and eruptive cyst. They could be misdiagnosed as oral potential malignant disorders, candidiasis, Human Papilloma Virus (HPV)-related affections, oral autoimmune diseases, or benign and malignant tumors. In some cases, pseudolesions feature in a syndromic panel, for example, fissured tongue in Melkersson-Rosenthal syndrome. It is strictly fundamental for dentists to know and to distinguish oral pseudolesions from pathological conditions, in order to avoid overtreatment. Pseudolesions are defined as physiological or paraphysiological changes of the oral normal anatomy that can easily be misdiagnosed for pathological conditions such as potentially malignant lesions, infective and immune diseases, or neoplasms. Pseudolesions do not require treatment and a surgical or pharmacological approach can constitute an overtreatment indeed. This review aims to describe the most common pseudolesions of oral soft tissues, their possible differential diagnosis and eventual related systemic diseases or syndromes. The pseudolesions frequently observed in clinical practice and reported in literature include Fordyce granules, leukoedema, geographic tongue, fissured tongue, sublingual varices, lingual fimbriae, vallate papillae, white and black hairy tongue, Steno's duct hypertrophy, lingual tonsil, white sponge nevus, racial gingival pigmentation, lingual thyroid, and eruptive cyst. They could be misdiagnosed as oral potential malignant disorders, candidiasis, Human Papilloma Virus (HPV)-related affections, oral autoimmune diseases, or benign and malignant tumors. In some cases, pseudolesions feature in a syndromic panel, for example, fissured tongue in Melkersson-Rosenthal syndrome. It is strictly fundamental for dentists to know and to distinguish oral pseudolesions from pathological conditions, in order to avoid overtreatment.

Objectives: To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain. Methods: In this case–control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann–Whitney U test and hierarchical multiple linear regression analysis, were used. Results: Poor sleep quality (PSQI≥5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p&nbsp

Abstract: Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans, normally a saprophyte of the oral cavity, may become virulent and infect the oral mucosa with variegated clinical presentation, in case of imbalance of the oral microbiota, the presence of local predisposing factors and systemic conditions that weaken the immune system. Conventionally, oral candidiasis eradication is done with the help of antifungal drugs. However, the growing phenomena of drug resistance and the increase in infections sustained by non-albicans species being less responsive to common antifungals have orientied researches towards the experimentation of alternative therapies. The present review considered the most promising alternative therapeutic proposals. The use of plant derivatives with phytotherapy is a promising option, such as probiotics, to rebalance the oral microbiota in case of dysbiosis. Finally, antimicrobial photodynamic therapy (aPDT), with highly selective fungicidal activity and free of side effects, is also being studied as a powerful alternative to drug administration. All these therapies are alternatives or supportive to the conventional treatment of recurrent and non-drug-responsive forms of oral candidiasis. However, further studies are needed to define the most active compounds, the efficacy of the therapies compared with the conventional ones, and the planning of regulated and standardized protocols.

Objectives: The aim of this systematic review was to estimate the osteoradionecrosis rate in patients with head and neck cancer due to teeth extraction performed before radiotherapy and to identify possible risk factors. Material and Methods: PRISMA protocol was used to evaluate and present the results. PubMed, Scopus and Web of Science were used as search engines: English full-length papers of clinical studies, in peer-reviewed journals, were investigated. Cumulative meta-analysis was performed with a random effects model (PROSPERO registration code: CRD42018079986). Results: Among 2,020 records screened, 8 were included in this review. Sixteen of 494 patients who underwent tooth extraction before radiotherapy developed osteoradionecrosis, with an osteoradionecrosis incidence of 2.2% (95% Confidence of Interval=0.6–3.9, p&nbsp

Objectives: This review aimed to evaluate the correlation between viral infections (HPV, EBV, HSV-1, CMV) other than HCV and oral lichen planus to assess if there is sufficient evidence to establish if these viruses can play a role in the etiopathogenesis of the disease. Materials and methods: We reviewed the literature using different search engines (PubMed, ISI Web of Science, and the Cochrane Library), employing MeSH terms such as “oral lichen planus” and “OLP” in conjunction with other terms. We utilized the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) method to define our study eligibility criteria. Results: A total of 43 articles of the 1219 results initially screened were included in the study. We allocated the 43 selected items into four groups, according to each related virus: HPV, EBV, HSV-1, and CMV. Conclusions: Heterogeneous results neither confirm nor exclude a direct correlation between the investigated viral infections and oral lichen planus etiopathogenesis and its feasible malignant transformation. Many viral agents can cause oral lesions and act as cancerizing agents. Future studies could be desirable to produce comparable statistical analyses and enhance the quantity and quality of the outcomes to promote the translation of research into clinical practice.

Objective The purpose of this study was to describe an unusual case of intraoral juvenile xanthogranuloma (JXG) and to perform a systematic review to investigate the available literature regarding oral JXGs. Study design We present a new case of oral JXG arising in a 36-year-old Italian woman and conducted a systematic literature review in PubMed, Web of Science and Scopus, according to the PRISMA guidelines. Results Our review of the English-language literature yielded 34 cases of oral JXG, which are included in our case report. Conclusions JXG is a non-Langerhans cell histiocytosis. Oral JXG has been reported, but it is a rare manifestation. Because of the rarity of oral lesions and possible variations in the clinical and histological presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathological evaluation with adjuvant immunohistochemical studies.

To assess (i) the prevalence of oral colonization by Candida spp. in patients with psoriasis and (ii) the prevalence of oral lesions associated with Candida spp. in patients with psoriasis and identify the risk factors for oral lesions. A systematic review was conducted in accordance with PRISMA criteria. The PROSPERO registration code is CRD42019127178. PubMed, Scopus and Web of Science were used as search engines. Meta-analyses and trial sequential analyses were performed. Among the 5805 retrieved records, nine articles were included. Among 530 psoriatic patients, 255 patients had an oral Candida spp. colonisation with an odds ratio (OR) = 3.44 (95% CI:2.38-5.00). Among 490 psoriatic patients, 43 patients developed oral Candida spp. lesions with an OR = 5.31 (95% CI:1.04-27.23). Among the patients without the main predisposing factors for infections, psoriatic patients had a higher OR (3.48, 95% CI: 2.0-6.0) for Candida spp. colonization, but not for Candida spp. infection, when compared with healthy controls (p-value > 0.05). Meta-analysis showed a higher risk of Candida spp. colonisation in patients with psoriasis. Patients who received immunosuppressive therapies were also at higher risk of developing oral lesions. Further studies are needed to understand these associations.

Simple Summary Oral squamous cell carcinoma (OSCC) accounts for 90–95% of malignant tumors of the lip and oral cavity and is associated with high mortality in the advanced stages. Early diagnosis is a challenge for oral pathologists and dentists, due to the ambiguous appearance of early OSCC, which is often misdiagnosed, mistreated, and associated with diagnostic delay. The gold standards for OSCC diagnosis are biopsy and histopathological assessment, but these procedures are invasive and time-consuming. Adjunctive noninvasive techniques allow the definition of the malignant features of a suspicious lesion in real time and noninvasively, thus improving the diagnostic procedure. The present review aimed to focus on some of the main promising noninvasive imaging techniques, to highlight their perspective adoption in a three-step diagnosis, which is idealistically faster and better, as well as enables the patient’s compliance. Abstract Oral squamous cell carcinoma (OSCC) is the most prevalent form of cancer of lips and oral cavity, and its diagnostic delay, caused by misdiagnosis at the early stages, is responsible for high mortality ratios. Biopsy and histopathological assessment are the gold standards for OSCC diagnosis, but they are time-consuming, invasive, and do not always enable the patient’s compliance, mainly in cases of follow-up with the need for more biopsies. The use of adjunctive noninvasive imaging techniques improves the diagnostic approach, making it faster and better accepted by patients. The present review aims to focus on the most consolidated diagnostic techniques, such as vital staining and tissue autofluorescence, and to report the potential role of some of the most promising innovative techniques, such as narrow-band imaging, high-frequency ultrasounds, optical coherence tomography, and in vivo confocal microscopy. According to their contribution to OSCC diagnosis, an ideal three-step diagnostic procedure is proposed, to make the diagnostic path faster, better, and more accurate.

Background: Saprochaete clavata infection is an emerging issue in immunosuppressed patients, causing fulminant fungaemia. The purpose of this systematic review of cases is to retrieve all cases of S. clavata infection and describe oral lesions as the first manifestation of S. clavata infection. Methods: We report the first case of intraoral S. clavata infection in Acute Myeloid Leukemia (AML) affected subject, presenting as multiple grayish rapidly growing ulcerated swellings, and provide a review of all published cases of infection caused by S. clavata, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, conducted by searching SCOPUS, Medline, and CENTRAL databases. Only articles in English were considered. Individual patient data were analyzed to identify risk factors for S. clavata infection. Results: Seventeen of 68 retrieved articles were included in the review reporting data on 96 patients (mean age 51.8 years, 57 males and 38 females). Most cases were disseminated (86) with a 60.2% mortality rate. Ninety-five were hematological patients, with AML being the most common (57 cases). Conclusions:S. clavata infection in immunosuppressed patients has a poor prognosis: middle-age patients, male gender and Acute Myeloid Leukemia should be considered risk factors. In immunosuppressed patients, the clinical presentation can be particularly unusual, imposing difficult differential diagnosis, as in the reported case.