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Objectives To compare the percentage of mean root coverage (MRC%) obtained in the treatment of multiple Miller class III/RT2 gingival recessions using the modified VISTA (m-VISTA) technique versus the coronally advanced flap (CAF) technique, using a connective tissue graft (CTG) in both cases. Materials and methods Twenty-four patients were randomly treated with m-VISTA (test group (TG) = 12) or CAF (control group (CG) = 12). A calibrated, experienced, and blinded examiner collected data related to multiple periodontal clinical variables, especially the recession (REC) in order to calculate the MRC% at 6 and 12 months, which was the primary outcome of the study. Also, the radiological bone level, the characteristics of the CTG, and postsurgical incidences were assessed. Finally, a descriptive and an analytical statistical analysis of the variables and their associations was performed. Results The recessions (n = 84) were located mainly in the mandible (n = 65) and in posterior sectors (premolars: n = 35; molars: n = 8). At 6 months, the MRC% was 61% (2 mm) for both study groups, and at 12 months, it increased to 73.26% (2.11 mm) in the TG and decreased to 56.49% (1.78 mm) in the CG. Conclusion When approaching multiple Miller class III/RT2 recessions, there were no statistically significant differences in the MRC% at 6 and 12 months between the group treated with the m-VISTA technique and the group treated with the CAF. Clinical relevance The characteristics of the m-VISTA technique, such as the closed approach, the mobilization of the papilla, and the coronal stabilization of the CTG, could facilitate the maturation of the tissues in the treatment of Miller class III/RT2 recessions. This would favor better root coverage. Trial registration NCT03258996.

Lymphomas affecting the sublingual glands are extremely rare and very few case reports are currently available. Therefore, the aim of the current study is to describe the clinicopathological features of a series of lymphomas involving the sublingual glands.Cases diagnosed in four pathology services were assessed and the formalin-fixed paraffin-embedded tissue blocks were retrieved for diagnosis confirmation. Clinical data were obtained from patients' medical files.We obtained seven cases of lymphomas in the sublingual glands, representing two follicular lymphomas, two diffuse large B cell lymphomas not otherwise specified (DLBCL NOS), two extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas) and one mantle cell lymphoma (MCL). In all cases the tumor cells infiltrated the glandular parenchyma, although in two of them the neoplastic cells were located more superficially and permeated the glandular acini and ducts. Clinically, the tumors presented as asymptomatic nodules and two patients (affected by DLBCL NOS and MCL) died, while the other five patients remained alive at last follow-up.Lymphomas affecting the sublingual glands are usually of the mature B cell lineage, often represent low-grade subtypes and may clinically resemble other more common lesions in the floor of the mouth like salivary gland tumors.

OBJECTIVE Oral leukoplakia (OL) is the most frequently encountered oral potentially malignant disorder. The aims of this systematic review are to estimate the overall malignant transformation of OL and to assess the risk factors associated with malignant transformation of OL published in the last 5 years (2015-2020). MATERIALS AND METHODS We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and Cochrane databases with keywords "oral leukoplakia", "oral cancer", "oral carcinoma" and "oral squamous cell carcinoma". Meta-analysis was conducted using a random-effects model. RESULTS Twenty-four studies were selected, that reported a total of 16,604 patients. Malignant transformation proportion varied between 1.1% and 40.8%. Female gender, non-homogeneous clinical type, and presence of epithelial dysplasia were significantly related to MT. Other risk factors previously suggested did not show significant results. CONCLUSIONS The pooled proportion of malignant transformation MT was 9.8% (95% CI: 7.9-11.7). It is necessary to continue to conduct well-designed prospective clinicopathological studies on OL, using a uniform definition for OL to reduce the risk of bias for evaluating various factors associated with the MT.

OBJECTIVE The aim of this study is to present and discuss the salient clinicopathological features, differential diagnosis and epithelial immunohistochemical profile of three additional cases of peripheral odontogenic keratocyst (POKC) and to present a review of the literature. POKC is a locally aggressive odontogenic lesion. The peripheral variant of the odontogenic keratocyst is rare and more frequently located in anterior gingiva. MATERIAL AND METHODS We present the clinicopathological features of 3 new cases of POKC (2 women and 1 man; age range: 14-74 years). Immunohistochemical study included CK7, CK14, CK19 and Ki-67, and a systematic review of the literature was performed in PubMed, Scopus and Web of Science databases. RESULTS All cases were located in the anterior gingiva (2 in maxilla and 1 mandible), and none corresponded to Gorlin-Goltz syndrome. High expression of CK14 was seen in all cases, with CK19 and CK7 been only focally positive. The expression of Ki-67 was located in the basal and parabasal cells in all cases. CONCLUSIONS POKC is a rare gingival lesion that seems to originate from remnants of dental lamina or from the basal cells of the gingival epithelium and present a similar histopathology as compared to intraosseous OKC.

[EN] Spontaneous resolution of pediatric obstructive sleep apnea (OSA) may stand behind the observed benefit of rapid maxillary expansion (RME), mainly supported by uncontrolled case series. We aimed to review the controlled, ideally randomized, evidence on the effectiveness of RME as compared to watchful waiting or alternative treatment of pediatric OSA. We only found one randomized clinical trial comparing RME with watchful waiting. The other four studies compared RME with the gold-standard treatment adenotonsillectomy, three of them in a non-randomized fashion. The results of the RCT showed no statistically significant differences in the enhancement of main (apnea hypopnea index, AHI) and secondary outcomes between RME and watchful waiting. Furthermore, reproducibility of the published studies was limited by insufficient description of their patients' inclusion criteria. We could not find convincing evidence of the benefit of RME over watchful waiting in patients with pediatric OSA. RCTs with reproducible inclusion criteria comparing RME with watchful waiting are still critically needed to support this intervention for the treatment of pediatric OSA. In the absence of solid evidence with RCT, RME should not be recommended for the treatment of pediatric OSA. PROSPERO REGISTRATION NUMBER: CRD42021249261. RUNNING SUMMARY: This systematic review explores the benefits of rapid maxillary expansion compared to spontaneous resolution of pediatric obstructive sleep apnea.

Oral squamous cell carcinoma (OSCC) commonly affects older patients; however, several studies have documented an increase in its incidence among younger patients. Therefore, it is important to investigate if this trend is also found in different geographic regions. The pathology files of diagnostic and therapeutic institutions from different parts of the globe were searched for OSCC cases diagnosed from 1998 to 2018. Data regarding the sex, age, and tumor location of all cases, as well as the histologic grade and history of exposure to risk habits of cases diagnosed as OSCC in young patients (≤ 40 years of age) were obtained. The Chi-square test was used to determine any increasing trend. A total of 10,727 OSCC cases were identified, of which 626 cases affected young patients (5.8%). Manipal institution (India) showed the highest number of young patients (13.2%). Males were the most affected in both age groups, with the tongue and floor of the mouth being the most affected subsites. OSCC in young individuals were usually graded as well or moderately differentiated. Only 0.9% of the cases occurred in young patients without a reported risk habit. There was no increasing trend in the institutions and the period investigated (p > 0.05), but a decreasing trend was observed in Hong Kong and the sample as a whole (p

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

Background Odontogenic keratocysts (OKC) are cystic lesions appearing in the jaws, usually asymptomatic with a progressive growth into the bone. Many of them are diagnosed by a routine radiological examination. Material and methods This study reports a 12-year-old girl that presented an asymptomatic large radiolucent unilocular lesion associated to the crown of 3.8 that caused displacement of the molar and the inferior alveolar canal. Differential diagnosis included OKC, unicystic ameloblastoma, ameloblastic fibroma, dentigerous cyst and orthokeratinized odontogenic cyst. Two surgical interventions were performed; first, a marsupialization, and 10 months after, the third molar extraction plus cyst enucleation, mucosa excision and the application of Carnoy's solution. Results The anatomopathological exam confirmed diagnosis of OKC. There was no evidence of recurrence after 2 years of follow-up. Conclusions Marsupialization followed by surgical enucleation with mucosa excision and Carnoy's solution can help manage treatment of OKC, a lesion characterized by an aggressive behavior. Key words:Odontogenic keratocyst, mucosa excision, carnoy solution, third molar, tooth extraction.

Background Peri-implantitis is the inflammatory process, which most commonly affects the therapy with dental implants. However, there are other reactive and neoplastic entities, mainly benign but also malignant, which also take place in the peri-implant mucosa. There is little information about the histopathological analysis of these peri-implant inflammatory diseases. Purpose To analyze the histopathological diagnosis of biopsies located in the peri-implant mucosa that showed an inflammatory clinical appearance. Materials and methods We have made a retrospective study of 111 peri-implant biopsies analyzed in the Oral and Maxillofacial Pathology Unit of the Dental Clinic Service at the University of the Basque Country, from January 2001 to December 2018. These samples corresponded to 84 women and 27 men, whose mean age was 59 years. We performed a standard histological processing with paraffin embedding, and sections were stained with H&E and PAS. All cases were analyzed following a specific diagnostic histopathological protocol. A descriptive statistical analysis was carried out with the obtained data. Results Lesions located in the mandible (64.8%) were more frequent and 34.2% of the biopsies arrived without a presumptive clinical diagnosis. "Inflammatory peri-implant lesion" or peri-implantitis was the most common clinical diagnosis. Histopathologically, the majority of the lesions were peri-implant nonspecific inflammatory hyperplasia (60.3%), followed by peripheral giant cell granuloma (18.1%), pyogenic granuloma (lobular capillary hemangioma) (14.4%), actinomicotic infection (3.6%), and squamous cell carcinoma (3.6%). Individually, peri-implant lesions were more common among women and in the mandible, except for actinomicotic infection and squamous cell carcinoma. Conclusions An important percentage of cases whose initial presumptive clinical diagnosis was "peri-implant inflammatory lesion" truly corresponded to other reactive and neoplastic processes. Thus, it is key to always submit all the tissue removed during the implant surgery, in order to perform a good histopathological study and achieve the correct final diagnosis.

Angina bullosa hemorrhagica (ABH) is a rare oral disorder characterized by blood-filled bullous lesions in the oral cavity and the oropharynx in the absence of an underlying systemic, haematological or mucocutaneous condition. The presentation of the lesions is acute and located on the lining mucosa, mainly on the soft palate. Often, these lesions are single and rupture easily leaving an ulcerated area. In this study, we present 4 ABH cases in 3 women and 1 man and we discuss the main clinicopathological characteristics. The characteristics of this disorder are important to recognize in order to differentiate the lesions from other oral bullous conditions of the oral cavity such as mucocutaneous disorders or blood coagulation disorders., peer-reviewed

Made available in DSpace on 2020-12-12T01:55:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 Objective: Granular cell tumour (GCT) is a benign neoplasm that originates from Schwann cells. Within the oral cavity, it usually appears as a lingual nodule and especially amongst female adults. Histologically, GCT shows a proliferation of polygonal cells with eosinophilic granular cytoplasm, which can be associated with a pseudoepitheliomatous hyperplasia (PEH). In this study, we analyse the main clinicopathological data of intraoral GCT and we compare our results with previous studies. Material and Methods: We have studied a series of 56 cases of oral GCT in Spain and Brazil, and we have conducted a systematic review in PubMed, Web of Knowledge and Scopus databases, using the keywords: “granular cell tumour” and oral. Results: In our series, GCT appeared as an asymptomatic benign tumour that is more frequent in women and in the tongue. PEH was observed in 32% of the lesions. In the review, we collected 282 cases of oral GCT with a similar clinical profile; seven patients had multiple lesions, and 33% of the cases presented PEH. No cases of malignant oral GCT have been described to date. GCT is an uncommon oral benign neoplasm, mainly unique and asymptomatic, derived from Schwann cells. Conclusions: Although the etiopathogenesis of this oral tumour is unknown, its characteristics suggest that it could have a reactive nature. Conducting a complete clinicopathological study in all intraoral GCT is fundamental in order to dismiss other entities, including oral carcinoma. Oral and Maxillofacial Pathology and Oral Medicine Unit Department of Stomatology II University of the Basque Country Special Care Dentistry Centre (CAPE) and Oral Pathology Department of Stomatology University of São Paulo School of Dentistry (USP) Mogi das Cruzes University Department of Bioscience and Oral Diagnosis Institute of Science and Technology of São José dos Campos São Paulo State University (Unesp) Oral Medicine Oral Surgery and Implantology Unit MedOralRes Group Universidade de Santiago de Compostela Instituto de Investigación Sanitaria de Santiago (IDIS) Department of Bioscience and Oral Diagnosis Institute of Science and Technology of São José dos Campos São Paulo State University (Unesp)

Objectives To investigate the molecular pathogenesis of implant-associated peripheral giant cell granuloma (IA-PGCG). Methods A convenience sample of 15 IA-PGCG cases was selected. Hotspot mutations of KRAS, FGFR1, and TRPV4 genes, previously reported in conventional giant cell lesions of the jaws, were investigated by Sanger sequencing. As these mutations could activate MAPK/ERK pathway, the expression of phospho-ERK1/2 was also evaluated by immunohistochemistry. Results KRAS mutations were detected in 8/15 (53.4%) samples. Similar to conventional peripheral giant cell granuloma, the KRAS mutations most frequently occurred in codon 146 (p.A146V, n = 3), followed by codon 12 (p.G12A and p.G12D, n = 1 each) and codon 14 (p.V14L, n = 1). Variants of unknown significance (VUS) were also detected in two cases, affecting codons 37 (p.E37K) and 127 (p.T127I). All samples showed wild-type (WT) sequences for FGFR1 and TRPV4 genes. Consistent with MAPK/ERK pathway activation, all mononuclear cells of the lesion showed strong staining for phospho-ERK1/2 protein in the immunohistochemical analysis. Conclusions KRAS mutations and activation of the MAPK-ERK signaling pathway occur in IA-PGCG. This is the first study to demonstrate cancer-associated gene mutations in a non-neoplastic reactive condition associated with dental implants.

Oral squamous cell carcinoma (OSCC) commonly affects older patients; however, several studies have documented an increase in its incidence among younger patients. Therefore, it is important to investigate if this trend is also found in different geographic regions. The pathology files of diagnostic and therapeutic institutions from different parts of the globe were searched for OSCC cases diagnosed from 1998 to 2018. Data regarding the sex, age, and tumor location of all cases, as well as the histologic grade and history of exposure to risk habits of cases diagnosed as OSCC in young patients (≤ 40 years of age) were obtained. The Chi-square test was used to determine any increasing trend. A total of 10,727 OSCC cases were identified, of which 626 cases affected young patients (5.8%). Manipal institution (India) showed the highest number of young patients (13.2%). Males were the most affected in both age groups, with the tongue and floor of the mouth being the most affected subsites. OSCC in young individuals were usually graded as well or moderately differentiated. Only 0.9% of the cases occurred in young patients without a reported risk habit. There was no increasing trend in the institutions and the period investigated (p 0.05), but a decreasing trend was observed in Hong Kong and the sample as a whole (p 0.001). In conclusion there was no increase of OSCC in young patients in the institutions investigated and young white females not exposed to any known risk factor represented a rare group of patients affected by OSCC.

BACKGROUND Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization. METHODS A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity. RESULTS From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published. CONCLUSIONS The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p

Background Although uncommon, mature small B-cell lymphomas may arise in the oral/maxillofacial area and oral pathologists must be aware of the key characteristics of these neoplasms to perform an accurate diagnosis. In this manuscript, we attempted to integrate the currently available data on the clinicopathological features of follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT-L), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) affecting these anatomical regions. Methods An updated descriptive literature review was carried out and a detailed electronic search was done in multiple databases to gather all cases affecting the oral/maxillofacial region and palatine tonsils. Results We observed that MALT-L was the most frequently reported subtype, followed by FL, MCL, and CLL/SLL. The palate was affected in a high proportion of cases and the most usual clinical presentation was an asymptomatic swelling. MALT-L and CLL/SLL neoplastic cells were strongly associated with small salivary glands. FL showed no gender preference, while MCL and CLL/SLL were more prevalent in males and MALT-L in females. Overall, cases were more common in elderly individuals. Patients' treatment and outcome varied, with MCL being the most aggressive neoplasm with a dismal prognosis in comparison to FL and MALT-L. Conclusion Despite the poor documentation in many of the cases available, especially regarding the microscopic and molecular features of tumors, this review demonstrated that the oral mature small B-cell lymphomas investigated share similar clinical presentation, but carry different prognostic significance, demanding an accurate diagnosis. The authors are grateful to the SAo Paulo State Research Foundation (FAPESP 2016/21785-4) for the student scholarship. Felipe Paiva Fonseca, Jean Nunes dos Santos, Pablo Agustin Vargas, and Manoela Domingues Martins are research fellows of the Brazilian National Council for Scientific and Technological Development (CNPq)

Objective The target of the current systematic review is to gather and synthesize the most recent scientific information about the role of Porphyromonas gingivalis in the molecular pathways of oral squamous cell carcinoma (OSCC). Background Oral squamous cell carcinoma is the most common malignancy of the oral cavity, with a poor prognosis and a low survival rate. Etiology is multifactorial but consumption of tobacco and alcohol is the most important risk factors. P gingivalis is a Gram-negative anaerobic bacterium commonly found in oral microbiota that has been linked to periodontal disease (PD), and recently to OSCC. However, its association with OSCC development is not well defined. Material and methods A bibliographic research was carried out selecting articles published until 2019, on PubMed, Web of Science, and Scopus databases, with the keywords "Porphyromonas gingivalis," "oral cancer," "oral squamous cell carcinoma," and "periodontal pathogen." Results Seventeen articles, 14 in vitro and three in animal models, were selected. Models mimicking OSCC were OSCC pre-established cell lines (11 studies), OSCC/ healthy human biopsies (three studies), and animals with OSCC (three studies). P gingivalis strains used to cause infection in these studies were ATCC 33277, 381, and W83. Conclusions Porphyromonas gingivalis could play an important role in OSCC development and could be involved in three different stages: epithelial-mesenchymal transition of malignant cells, neoplastic proliferation, and tumor invasion. Current findings emphasize the convenience of treatment and control approaches of PD as part of the primary prevention of OSCC.

Background Juvenile spongiotic gingival hyperplasia (JSGH) is a distinct clinicopathological entity of the buccal gingiva of young patients which has been related to several factors such as plaque formation, hormonal modifications, and viral infections; however, its true etiopathogenesis remains unsolved. Several immunohistochemical studies have demonstrated the similarity between the junctional epithelium (JE) and the hyperplasic epithelium of JSGH. The objective of this study is to analyze the clinicopathological and immunohistochemical characteristics of JSGH to explain its origin. Methods Clinicopathlogical data of 10 cases of JSGH (five men and five women) with a mean age of 13 years (range: 9 to 17 years) were collected. CK7, CK14, CK19, CD3, CD20, S100, and Ki-67 antibodies were used for comparative immunohistochemical study. Results All the lesions showed hyperplasic epithelium in its central portion, exhibiting marked spongiosis, vascular proliferation, and a chronic inflammatory infiltrate on the subepithelial connective tissue. CK19 was positive in the whole hyperplasic epithelium of JSGH and the basal layer of the marginal gingiva, while expression of CK14 was present in all epithelial layers of both the JSGH and that of the marginal gingiva. The subepithelial inflammatory infiltrate has a larger amount of CD20 positive cells. Conclusion JSGH is a reactive tumor of the gingiva that may have an odontogenic etiology, whose origin seems to be the remnants of JE.

Background Lipomas are benign neoplasms derived from adipose tissue that are unfrequently found in the oral cavity. The objective of this study is to identify the main clinicopathological characteristics of this tumour in a case series of oral lipomas (OL) in a population from Spain and Brazil. Material and methods A multicentre retrospective observational study was conducted in collaboration with the Oral Pathology Unit of the Sao Paulo State University (UNESP), Sao Jose dos Campos, in Brazil, and the Oral Medicine and Pathology Units of the University of Santiago de Compostela (USC) and the University of the Basque Country (UPV/EHU) in Spain. Results This multicentre series consists of a total of 97 of OL cases, 31 (32%) of which correspond to Spain, and 66 (68%) to Brazil with an overall prevalence of 0.33%. The average age of the patients is 56.44 years old, with a range of 10-92 (SD = 15.52). Buccal mucosa was the most frequent location (42.3%). Cases from Spain coexisted with other lesions in a significant number of cases, 12.9%, vs Brazil, 1.5% (P = 0.018). According to the progression time, Brazil has an average of 60.35 months (CI: 27.20-93.51), compared to 5.41 months in Spain (CI: 3.17-7.65) (P = 0.022). Average size is 12.55 mm (SD = 11.06), ranging from 2 to 75 mm. A positive correlation is also seen between the increase in the lesion size and a greater progression time (CC = 0.367; P = 0.008). Conclusions Correct differential diagnosis of the clinical lesion is key, followed by a good histopathological study, to achieve the final diagnosis.

Aims: To discuss the terminology to define and classify actinic cheilitis (AC) and to build a consensus on the diagnostic and therapeutic approaches to AC. Methods: Two-round Delphi study using a questionnaire including 34 closed sentences (9 on terminology and taxonomy, 5 on potential for malignant transformation, 12 on diagnostic aspects, 8 on treatment) and 8 open questions. Experts’ agreement was rated using a Likert scale (1–7). Results: A consensus was reached on 24 out 34 statements (73.5%) and on 5 out of 8 (62.5%) close-ended questions. The response rate was identical in both rounds (attrition of 0%). AC is the term with the highest agreement (median of 7 (strongly agree; IQR: 6–7)) and the lowest dispersion (VC = 21.33). ‘Potentially malignant disorder’ was the preferred classification group for AC (median of 7) and 85.6% of participants showing some level of agreement (CV < 50). Experts (66.75%) consider AC a clinical term (median: 7; IQR: 4–7) and believe definitive diagnosis can be made clinically (median: 6; IQR: 5–7), particularly by inspection and palpation (median: 5; IQR: 4–6). Histopathological confirmation is mandatory for the management of AC (median: 5; IQR: 2.5–7), even for homogeneous lesions (median: 5; IQR: 3.5–6). Consensus was reached on all treatment statements (VC < 50). Conclusions: AC is a potentially malignant disorder with a significant lack of agreement on diagnostic criteria, procedures, biopsy indications and the importance of techniques to assist in biopsy. A consensus was reached on nomenclature and management of this disorder SI

An amendment to this paper has been published and can be accessed via the original article.

Background The primary objective of this systematic review and meta-analysis was to assess the evidence on complete root coverage (CRC) achieved by periodontal plastic techniques in the treatment of Miller class III/RT2 gingival recessions, comparing techniques developed along the twentieth century (pre-twenty-first) versus surgical approaches of the twenty-first century (21st). Methods An electronic bibliographic search was carried out in four databases up to December 2019, focusing on studies that reported CRC results in Miller class III or RT2 recessions treatment with at least a six-month follow-up. In addition, a random-effects models’ meta-analysis was performed for the CRC, comparing pre-twenty-first versus twenty-first century techniques at 6 months, 12 months and more than 12 months. Results Thirty-seven publications were included. A total of 933 gingival recessions were treated, 298 with pre-twenty-first century surgical techniques and 635 with techniques from the twenty-first century. CRC was achieved at 6 months on half of the recessions (pre-twenty-first: 57.60% vs. 21st: 51.11%), but decreased markedly for twenty-first century techniques at 12 months (pre-twenty-first: 63.82% vs. 21st: 32.87%). Thereafter, this difference was the other way around (> 12 months: pre-twenty-first: 5.26% vs. 21st: 19.65%). The meta-analysis showed a high heterogeneity, with no significant differences amongst the techniques. Conclusions Although CRC might be achievable by treating Miller class III or RT2 recessions with any of the described techniques, its long-term stability is not predictable. More randomized clinical trials with longer follow-ups and several visits, are needed. In addition, the patient’s satisfaction should also be assessed.

Background: To perform a systematic review and meta-analysis on the presence of IL-1β polymorphisms in patients with peri-implantitis (PI). PI is the main complication associated to dental implant therapy. Although its main risk factors are history of periodontitis, poor plaque control and lack of regular maintenance, genetic susceptibility could also be a determinant factor for its appearance. Single nucleotide polymorphisms (SNP) are small mutations of the DNA, that alter the osseointegration of implants. Interleukin 1β (IL-1β) is an inflammatory protein that participates in both destruction of the extracellular matrix and reabsorption of the alveolar bone.Methods: A bibliographical research was made in PubMed, Scopus and Web of Science (keywords: "single nucleotide polymorphism", “polymorphism”, "periimplantitis", "SNP" and "implant failure"). Results: There is no significant relation between of IL-1β (+3953) SNP and PI, but there is a statistically significant association of peri-implant bone loss with the homozygotic model of IL-1β (-511) (I2=0%, p=0.555; OR: 2.255; IC: 1.040-4.889)Conclusions: Absence of a strong link between of IL-1β polymorphisms and PI must be taken with caution due to the heterogeneous methodological design, sample size and diagnostic criteria of the studies. Thus, more well-designed studies are needed, that analyse the relationship between IL-1β polymorphism and PI.

Background The fourth edition of the World Health Organization Classification of Head and Neck Tumors was published in January 2017, and includes a classification of odontogenic tumors and odontogenic cysts. The present review assesses the changes made in this new classification in relation to odontogenic and non-odontogenic jaw cysts. Material and methods An electronic search was conducted in the Cochrane Library, PubMed-MEDLINE and Scopus databases using the search terms: "odontogenic cyst" "WHO classification" "update". Studies written in English and published between January 2005 and April 2020 with a high level of scientific evidence were included, while studies not published in English, epidemiological studies, and studies with a low level of scientific evidence were excluded. Results The initial search identified 311 articles, and after the deletion of duplicates, 7 studies were selected for full-text assessment. After excluding two studies that failed to provide relevant information and had a low level of scientific evidence, 5 articles were finally included and stratified according to their level of scientific evidence based on the SORT (Strength of Recommendation Taxonomy) criteria. Conclusions The incorporation of odontogenic and non-odontogenic cysts to the head and neck tumors classification underscores the recognition of the WHO of these important disorders of the jaws. Based on the current evidence, there is controversy as to whether odontogenic keratocysts should be regarded as cystic lesions or as neoplasms, though there is no such controversy in relation to calcifying odontogenic cysts. On the other hand, orthokeratinized odontogenic cysts have been included in the classification as a single entity differentiated from odontogenic keratocysts, while residual cysts have been removed from the classification. Key words:Odontogenic cyst, WHO classification, pseudocyst.

[EN]Oral candidiasis is frequently associated with Candida biofilms. Biofilms are microbial communities related to persistent, recalcitrant and difficult to-treat infections. Conventional treatments are not sufficient to overcome biofilm-associated candidiasis; thus, the search of new antifungal compounds is necessary. In the current study, we have evaluated the effect of three phytocompounds, carvacrol, cinnamaldehyde and thymol, against Candida planktonic and sessile cells. Reduction in biofilm biomass and metabolic activity was assessed during adhesion and mature biofilm phases. Candida albicans was the most biofilm-producing Candida species. All phytocompounds tested were fungicidal against Candida planktonic cells. Cinnamaldehyde was the most active in inhibiting biofilm adhesion, but carvacrol and thymol significantly reduced both mature biofilm biomass and metabolic activity. These results highlight the role of cinnamaldehyde, carvacrol and thymol as promising alternatives for the treatment of candidiasis due to their antibiofilm capacities, and stress the necessity to continue studies on their safety, toxicity and pharmacodynamics and pharmacokinetics. This work was supported by Gobierno Vasco-Eusko Jaurlaritza, Spain [grant number GIC15/78 IT-990-16, 2016] and Fundacion ONCE "Oportunidad al Talento", Spain and Fondo Social Europeo, Spain [CMA, 2018].

Additional file 1. Excluded studies and reasons for their exclusion. The additional file 1 shows a table including all the excluded studies and the reasons of their exclusion. All the references of these excluded studies are inside the additional file 1.

Background The fourth edition of the ‘’WHO Classification of Head and Neck Tumours’’ was published in January 2017 and includes a classification of odontogenic tumours. This review aims to examine the changes made in this new classification in comparison with the previous classification of 2005. Material and Methods An electronic search was conducted in the PubMed, Scopus and Cochrane databases with the keywords “odontogenic tumor”, “WHO classification” and “update”. Studies published from January 2009 to April 2019 with a high level of scientific evidence were included, but studies not published in English, epidemiological studies and studies with a low level of evidence were excluded. Results The initial search found 457 articles and after eliminating duplicates, 8 studies were selected for full-text assessment. After excluding 3 epidemiological studies, 5 articles were finally included. These studies were stratified by their level of scientific evidence using SORT criteria (Strength of Recommendation Taxonomy). Conclusions The new odontogenic tumour list has been simplified with the objective of improving its role as an international guide for diagnosis. Some changes have been possible thanks to the application of immunohistochemistry and molecular genetic techniques that allow better characterization of certain tumours. Further clinicopathological and molecular studies are needed so that this new classification can be consolidated and/or amended. Key words:Odontogenic tumour, WHO classification, update.

Candida can be implicated in the pathology of chronic periodontitis.To analyze the oral Candida carriage in patients suffering from chronic periodontitis (CP) and its correlation with the severity of this condition.Microbiological samples were taken from 155 patients using the oral rinse (OR) technique and by using paper points in the periodontal pockets (GPP). These patients were divided into 3 groups: 89 patients without CP (control), 47 with moderate CP, and 19 with severe CP. Samples were cultured in a Candida chromogenic agar for Candida. Species were identified by microbiological and molecular methods.Candida was isolated in the OR of 45 (50.6%), 21 (44.7%), and 11 (57.9%) patients, respectively, and in the GPP of 32 (36%), 14 (29.2%), and 10 (42.6%) patients from the control, moderate CP and severe CP groups, respectively. Candida was isolated more frequently and in a greater burden in OR than in GPP (p0.01). Candida albicans was the most prevalent species. GPP of patients with CP had poor fungal biodiversity (p0.01).Colonization by Candida was present in the samples of patients without CP, and with both moderate and severe CP. Nonetheless, patients with severe CP had a higher rate of Candida colonization, especially by C. albicans.

Background Odontogenic myxoma (OM) is a benign intraosseous neoplasm that exhibits local aggressiveness and high recurrence rates. Osteoclastogenesis is an important phenomenon in the tumor growth of maxillary neoplasms. RANK (Receptor Activator of Nuclear Factor κappa B) is the signaling receptor of RANK-L (Receptor activator of nuclear factor kappa-Β ligand) that activates the osteoclasts. OPG (osteoprotegerin) is a decoy receptor for RANK-L that inhibits pro-osteoclastogenesis. The RANK / RANKL / OPG system participates in the regulation of osteolytic activity under normal conditions, and its alteration has been associated with greater bone destruction, and also with tumor growth. Objectives To analyze the immunohistochemical expression of OPG, RANK and RANK-L proteins in odontogenic myxomas (OMs) and their relationship with the tumor size. Material and Methods Eighteen OMs, 4 small ( 3cm) and 18 dental follicles (DF) that were included as control were studied by means of standard immunohistochemical procedure with RANK, RANKL and OPG antibodies. For the evaluation, 5 fields (40x) of representative areas of OM and DF were selected where the expression of each antibody was determined. Descriptive and comparative statistical analyses were performed with the obtained data. Results There are significant differences in the expression of RANK in OM samples as compared to DF (p = 0.022) and among the OMSs and OMLs (p = 0.032). Also a strong association is recognized in the expression of RANK-L and OPG in OM samples. Conclusions Activation of the RANK / RANK-L / OPG triad seems to be involved in the mechanisms of bone balance and destruction, as well as associated with tumor growth in odontogenic myxomas. Key words:Odontogenic myxoma, dental follicle, RANK, RANK-L, OPG, osteoclastogenesis.

Objectives The aim of this study was to identify the possible association between TLR polymorphisms and an increased risk of developing head and neck cancer, including oral (OSCC) and laryngeal squamous cell carcinoma (LSCC), and oral potentially malignant disorders, such as oral lichenoid disease (OLD), including oral lichen planus (OLP) and oral lichenoid lesions (OLL). Design This case-control study included 40 OSCC, 35 LSCC, 175 OLD (129 OLP and 46 OLL) patients and 89 healthy controls, all of them from the Basque Country, Spain. Genetic polymorphisms in TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 were genotyped by TaqMan® assays or pyrosequencing. Results The chi-square analysis showed that the variant A of the SNP TLR2-rs4696480 polymorphism significantly increased the risk of OSCC (p = 0.03) and OLL (p = 0.02). Conclusions The TLR2-rs4696480 polymorphism may be relevant to OSCC and OLL susceptibility in this population encouraging further studies on the TLR2 pathway and its possible association with this group of oral potentially malignant disorders and oral cancer. This may also prove the use of TLR polymorphisms as risk markers for oral and laryngeal cancer.

Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.

Subepithelial connective tissue graft (SCTG) is considered the gold standard for treatment of gingival recessions. For ethical reasons, most studies report only clinical and not histologic results. A 20-year-old woman presenting with a localized gingival recession of 5 mm in the mandibular left central incisor was treated with SCTG. According to the initial treatment plan, the tooth was extracted 11 months later and a histologic study was performed, revealing new attachment of connective tissue with collagen fibers that were directly inserted in a perpendicular way into dentin areas and new cement areas (1.37 mm).

Objective To validate oral exfoliative cytology in the analysis of the microRNA expression profile in oral lichenoid disease (OLD). Study Design The expression of 13 microRNAs was analyzed in 26 cases, 16 diagnosed as OLD and 10 controls with no oral mucosal pathology. Cytologic samples from the oral mucosa obtained using an Orcellex toothbrush were analyzed using reverse transcription-quantitative polymerase chain reaction and TaqMan microRNA assays. Results The aberrant expression was validated for 2 microRNAs (miR-146 a-5 P and miR-7-1-3 P) of those previously recognized in the biopsy study. Conclusion This is the first time that oral exfoliative cytology is validated in a microRNA study in OLD. The microRNAs validated in this study are associated with both inflammatory and carcinogenic phenomena that are involved in the etiopathogenesis of this potentially malignant oral disorder.

Pemphigus vegetans is a chronic mucocutaneous autoimmune blistering disease that can involve oral mucosa, whose behavior is normally benign. We present a case of a 50-year-old man with an unremarkable past medical history who smokes 20 cigarettes every day. For the last 3 months, he has complained of pain on the gums. Clinical examination showed multiple white plaques on the buccal gingiva of all 4 quadrants, with a verrucous appearance, some of which had a reddish area. Incisional biopsies were performed of the lesions from the gingiva with clinical diagnosis of proliferative multifocal leukoplakia as well as a microbiologic culture intake. Histopathologic analysis, showing a verrucous epithelial hyperplasia with acantholysis, confirmed the diagnosis of verrucous pemphigus vegetans. Indirect immunofluorescence results for desmoglein 1 and 3 were negative. The patient remains under control after treatment with deflazacort and triamcinolone. This research was supported by a research group from UPV/EHU.

Background To validate oral exfoliative cytology in the analysis of the microRNA expression profile in Oral Lichenoid Disease (OLD)., Material and Methods The expression of 13 microRNAs identified and presented by our group in a previous study was analyzed in 26 cases, 16 diagnosed as OLD and 10 controls with no oral mucosal pathology. Cytological samples from the oral mucosa obtained using an Orcellex toothbrush were analyzed using RT-qPCR and TaqMan microRNA assays., Results The aberrant expression was validated for 2 microRNAs (miR-146a-5p and miR-7-1-3p) of those previously recognized in the biopsy study., Conclusions This is the first time that oral exfoliative cytology is validated in a study of the alterations of the expression of microRNAs in OLD. The alteration of miR-146a and miR-7 compared to controls was validated. These microRNAs are associated with both inflammatory and carcinogenic phenomena that are involved in the etiopathogenesis of this potentially malignant oral disorder., peer-reviewed

Background Few cases or peri-implant peripheral giant cell lesions (PGCL) have been reported in the literature. The aim of this study was to report 13 new cases of peri-implant PGCL and compare the expression of smooth muscle actin, Bcl-2 protein, GLUT-1, CD68, osteoprotegerin, receptor activator of nuclear factor kappa-B, Ki-67 and CD34 in these cases with PGCL and central giant cell lesions (CGCL). Material and Methods Clinical data were retrieved from the laboratory records and histological analysis was performed using HE-stained slides. Immunohistochemical reactions for the above mentioned antibodies were performed and digitally scored. Results Peri-implant PGCL mostly affected the posterior mandible of adult females. CD68 and Bcl-2 expressions were higher in conventional PGCL and CGCL than in peri-implant PGCL (p=0.033 for CD68 and p