Variations of oral anatomy and common oral lesions.

Several topics related to the oral cavity are briefly addressed in this article, from anatomical variations that, when recognized, avoid unnecessary investigations, to diseases that affect exclusively the mouth, mucocutaneous diseases, as well as oral manifestations of systemic diseases. A complete clinical examination comprises the examination of the mouth, and this approach facilitates clinical practice, shortening the path to diagnosis in the outpatient clinic as well as with in-hospital patients. The objective of this article is to encourage the examination of the oral cavity as a useful tool in medical practice, helping to recognize diseases in this location.

Oral erythroplakia and oral erythroplakia-like oral squamous cell carcinoma - what's the difference?

BACKGROUND: Oral erythroplakia (OE) is a rare oral potentially malignant disorder, that has a high rate of malignant transformation. The definition of OE still lacks uniformity. In particular, lesions that look clinically like erythroplakias, but are histopathologically diagnosed as squamous cell carcinomas are still sometimes called erythroplakias. The purpose of this study is to present demographic and clinicopathologic features of a series of OEs and clinically oral erythroplakia -like squamous cell carcinomas (OELSCC), to study their differences and to discuss the definition of OE. METHODS: A multicenter retrospective case series of OEs and OELSCCs. Descriptive statistics were used to analyze the data. RESULTS: 11 cases of OEs and 9 cases of OELSCCs were identified. The mean age of the OE patients was 71 years and 72.7% were female, while the mean age of the OELSCC patients was 69 years, and all were female. 9% of the OE and 22% of the OELSCC patients had smoked or were current smokers. 72.7% of the OEs and 55.5% of OELSCCs were uniformly red lesions. 63.6% of the OE and 22% of the OELSCC patients had a previous diagnosis of oral lichenoid disease (OLD). The malignant transformation rate of OE was 9% in a mean of 73 months. CONCLUSIONS: OE and OELSCC may arise de novo or in association with OLD. Tobacco and alcohol use were not prevalent in the present cases. The clinical features of OEs and OELSCC are similar, but symptoms, uneven surface and ulceration may be more common in OELSCCs than in OEs. Clinical recognition of OE is important since it may mimic other, more innocuous red lesions of the oral mucosa. The diagnosis of OE requires biopsy and preferably an excision. Clarification of the definition of OE would aid in clinical diagnostics.

Prevalence and Distribution of Oral Mucosal Lesions and Normal Variants among Nepalese Population.

Background: Oral mucosa is encountered by various lesions and normal variants. Some are not to be worried about, whereas others may be of significance. Knowing the prevalence of oral mucosal lesions in a particular region helps better evaluate, diagnose, and, thus, manage these lesions. Objectives: To assess the prevalence and distribution of oral mucosal lesions and normal variants among various age groups, genders, and sites of the orofacial region. Methods: This cross-sectional study was conducted in the Department of Oral Medicine and Radiology, KIST Medical College and Teaching Hospital from January 2021 to March 2021. Three different proformas were designed according to age, gender, and location of lesions for entry as per the WHO's guide. The obtained data were entered into a Microsoft Excel sheet for frequency analysis by SPSS, and the results were tabulated. Results: Among the records of 16572 (9703 (58.55%) males and 6869 (41.44%) females) OPD patients, 3495 (21.08%) (1934 (55.33%) males and 1561 (44.66%) females) had OMLs and 2314 (13.96%) (1626 (70.26%) males and 688 (29.73%) females) had normal mucosal variants. The most commonly seen OML categories were tobacco-associated lesions, i.e., 2056 (34.07%), tongue lesions, i.e., 1598 (26.48%), oral potentially malignant disorders, i.e., 815 (13.50%), ulcers i.e., 728 (12.06%), and infectious lesions, i.e., 256 (4.24%). Conclusion: The Nepalese population has a wide range of oral mucosal lesions and normal variants, and this study has attempted to have baseline data for the same. The most common OML was smoker's melanosis.

An unusual case of linear IgA disease affecting only the oral gingiva: a case report.

BACKGROUND: We present a case report on desquamative gingivitis diagnosed as linear IgA disease (LAD), which is a rare autoimmune bullous disease exclusively affecting the oral gingiva. The oral mucosa can be impacted by various autoimmune bullous diseases, and our report focuses on this particular manifestation of LAD. CASE PRESENTATION: This patient presented with atypical symptoms, as frequent blister formation on the gingiva was the primary clinical manifestation. A combination of systemic and local treatment was administered to the patient. Following the treatment, there was a significant improvement observed in both the erythema and the bullous lesions on the gingiva. CONCLUSIONS: A more suitable local treatment strategy should be formulated for patients presenting with oral topical lesions, which clinicians can employ effectively.

[Ulcerations of the oral mucosa]. / Ulceraties van het mondslijmvlies.

Ulceration is a common presenting sign of a wide spectrum of diseases of the oral cavity involving many etiologic factors, such as trauma, infection, neoplasms, medication, and immune related disorders, ranging from self-limited lesions to life-threatening diseases. In most cases, a proper diagnosis can be established based on medical history and clinical features only. Early diagnosis is important as oral ulcerations might be a manifestation of a systemic disease or sometimes even due to a malignant process.

Top Ten Lymphoproliferative Lesions Not to Miss When Evaluating Oral Ulcer Biopsies.

BACKGROUND: Oral ulcers represent a full thickness loss of the mucosal epithelium leading to exposure of the submucosal connective tissue. These are common and usually self-limited lesions, although they may sometimes result from neoplasms, most commonly squamous cell carcinoma. Lymphoproliferative disorders may be difficult to diagnose in apthous ulcers since they mimic reactive inflammation. METHODS: This review presents ten rare oral lymphoid proliferations which should not be missed when assessing oral ulcer biopsies. RESULTS: The ten lesions include several with diagnostic cells which look similar to the histiocytes of a reactive inflammatory ulcer, including Rosai-Dorfman disease, reticulohistiocytoma, Langerhans cell histiocytosis, and traumatic ulcerative granuloma. Other lesions, such as EBV-positive mucocutaneous ulcer, extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue, and plasmablastic lymphoma have lymphoid and/or plasma cell differentiation that mimic the reactive lymphocytes and plasma cells found in reactive ulcers. Two dendritic cell lesions, follicular dendritic cell sarcoma and blastic plasmacytoid dendritic cell neoplasm, both have distinct phenotypes which are required to make an accurate diagnosis. CONCLUSION: Each of these lesions are diagnosed by evaluating their histology, along with their phenotypic profile, which is sometimes enhanced by pertinent molecular findings.

A Man With Asymptomatic Ulcerated White Plaques on the Soft Palate.

A man in his 60s had irregular gray-white ulcers with a surrounding erythema on the soft palate, uvula, and tonsils that did not improve with oral cefuroxime. He reported sexual contact with 1 male partner over the prior 6 months; history and physical examination findings were otherwise unremarkable. What is the diagnosis and what would you do next?

Extracapsular dissection (ECD) and extended ECD: description of the technique and outcome of treatment.

Over the last two decades the senior author has exclusively applied the technique of extracapsular dissection (ECD) and extended ECD to treat discrete, apparently benign parotid tumours. This article describes both techniques and evaluates their application. Simple principles are described to anticipate unexpected malignant tumours and manage lumps safely by wide excision. A retrospective analysis of 97 consecutive patients with discrete, apparently benign parotid lumps is presented. The tumours were classified using the European Salivary Gland Society (ESGS) classification for benign tumours of the parotid gland. The ECD or extended ECD technique was employed irrespective of tumour site or size. A review of patients was carried out after a minimum of six months post surgery by two independent clinicians. The mean (range) hospital stay was one (0-4) night (median 1). Complications were both modest and transient. The temporary facial nerve injury rate was 5/97 (6%). Other complications included haematoma (n=2), sialocele (n=2), and first-bite syndrome (n=2). Independent review post surgery demonstrated a mean Sunnybrook facial grading system score of 98/100 and a mean Stony Brook scar assessment score of 4.5/5. In this series 5/97 (5%) of discreet mobile lumps concealed a low-grade salivary cancer. Experience with the application of ECD in conjunction with its extended form in 97 consecutive patients with discrete parotid lumps is described. The technique is amenable to all parotid lumps, is not restricted by site or size, and has shown minimal morbidity. The risk of recurrent disease could not be addressed.

Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats.

Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.

In vivo evaluation of traumatic and malignant oral ulcers with optical coherence tomography: A comparison between histopathological and ultrastructural findings.

Ulcers in the oral mucosa is a relatively common, although challenging, entity in oral medicine, as it can arise due to a wide range of traumatic, infective, autoimmune, and neoplastic disorders. Although histopathology of lesional and peri­lesional tissues remains the gold standard for persistent oral breaching, optical coherence tomography (OCT) has been recently suggested as a potential ally to enhance the early or non-invasive diagnosis of likely causation. The aim of the present study was to provide an in-vivo OCT analysis and description from a sample of 70 patients affected by traumatic or neoplastic-related ulcers, located on the buccal mucosa, tongue or gingiva, and compare the OCT data with those of 20 patients with healthy oral mucosa. OCT dynamic scans revealed clear distinction of epithelial layer (EP), lamina propria (LP) of healthy buccal mucosa, gingiva, and tongue as well as allowing observation of the keratin layer in gingiva, and the subepithelial vascularization of each site. Traumatic lesions had an EP of reduced in thickness, with an irregular, if not disrupted surface. Interestingly, LP seemed to preserve its reflectiveness and vascularization only in the traumatic lesions. Among neoplastic lesions, regardless their site of onset, both EP integrity/homogeneity, and LP reflectiveness/vascularization were lost and unrecognizable when compared to their healthy counterparts. OCT scanning allowed some differentiation between traumatic and malignant ulcers and thus may a useful and non-invasive means of determining the need and/or urgency of histopathological examination of oral lesions.

Critical update, systematic review, and meta-analysis of oral erythroplakia as an oral potentially malignant disorder.

BACKGROUND: Oral erythroplakia has been classically considered as the potentially malignant disorder with the highest rate of malignant development into squamous cell carcinoma. This critical systematic review and meta-analysis aim to estimate the malignant development rate of oral erythroplakia and identify the associated risk factors. METHODS: We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and LILACS, with keywords "erythroplakia," "erythroplasia," "malignant transformation," "malignant development," "malignization," "carcinogenesis," "oral cancer," "oral squamous cell carcinoma," "mouth neoplasm," and "prognosis." Meta-analysis was conducted using a random-effects model. RESULTS: Ten observational studies with 441 patients met the inclusion criteria, whose mean malignant development rate was 12.7% and with a mean follow-up period of patients of 6.66 years. In the initial biopsy, 42.8% of oral erythroplakia were already squamous cell carcinoma. The buccal mucosa was the most frequent location of oral erythroplakia, but the floor of the mouth was the most common site of malignant development. All patients who underwent malignant development showed epithelial dysplasia on the initial diagnostic biopsy. CONCLUSION: Overall malignant development rate of OE in the meta-analysis was 19.9%. We could not associate any specific clinicopathological feature with the malignant development. The presence of epithelial dysplasia in the initial biopsy remains the worst prognostic factor. Further observational studies on OE are needed, with well-established diagnostic criteria and good clinical follow-up, in order to identify the true risk of malignant development of oral erythroplakia and the related risk factors.

Simplifying assessment of dimensions of oral lesions using a syringe and 'impression planimetry' with printer paper.

Two novel methods of measuring the dimensions of oral lesions are described, which would be of help in deciding relative efficacies of different therapeutic agents when used in clinical trials after larger studies quantitatively assessed for inter/intraobserver variability.

Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model.

Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca2+ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca2+ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL® are needed to sufficiently induce the therapeutic effects.

Úlcera eosinofílica lingual: a propósito de un caso clínico / Eosinophilic ulcer of the tongue: case report

Introducción: La úlcera eosinofílica es una lesión infrecuente y benigna de la mucosa oral, caracterizada por su rápida instauración y evolución crónica. Su localización, predominantemente lingual; su aspecto con fondo necrótico de bordes indurados, y largo período de cicatrización, hacen que sea imprescindible su diagnóstico diferencial con un cáncer oral de células escamosas. Se atribuye su causa a un agente traumático, siendo este ausente en la mitad de los casos. Histológicamente, presenta un denso infiltrado inflamatorio polimorfo, con eosinófilos de tamaño aumentado. Objetivo: Se presenta un caso clínico de úlcera eosinofílica y una revisión bibliográfica actualizada con el objetivo de analizar sus factores etiológicos y sus opciones terapéuticas. Caso clínico: Paciente, mujer de 75 años, con una úlcera en el borde lingual derecho, de 1 cm de diámetro y 4 meses de evolución acompañada de un dolor intenso. En un período de 3 meses, se biopsió dos veces por su recidiva. En ambas biopsias, el estudio anatomopatólogico confirma la presencia de una intensa displasia epitelial, con un denso infiltrado inflamatorio, sin evidencia de un proceso neoplásico. Posteriormente, se trató con la aplicación tópica en gel de acetónido de triamcinolona al 0,5%, con el que la lesión curó en tres meses. Conclusión: La úlcera eosinofílica posee una etiopatogenia indeterminada. El agente traumático, se establece como factor predisponente. La biopsia es la medida principal para el diagnóstico y tratamiento de la lesión. Aunque no queda demostrada la eficacia de la aplicación de corticoides tópicos, suponen una mejoría en la evolución y sintomatología de la lesión. (AU)

Introduction: The eosinophilic ulcer is a rare benign lesion of the oral mucosa. It is known for its rapid onset and chronic course. Due to its main location, the tongue, clinical features and its slowhealing process, a differential diagnosis with oral squamous cell carcinoma is necessary. It is suggested that it is caused by local trauma, yet it is missing in half of the cases. The histopathological findings include dense polymorphic inflammatory infiltrate, with large eosinophils. Objective: We aim to report a case of eosinophilic ulcer and an updated literature review to analyse its etiological factors and treatment options. Case report: We present a case of a 75-year-old woman, with a painful ulcer in the right border of the tongue, which appeared 4 months ago. It had a diameter of 1 cm. In a period of 3 months, it had been biopsied twice, due to its recurrence. Both histological findings confirm the presence of a dense polymorphic inflammatory infiltrate, epithelial dysplasia and no neoplastic evidence. Afterwards, the lesion was treated with topical application of triamcinolone acetonide 0.5% and it healed within 3 months. Conclusion: Eosinophilic ulcer has an undetermined etiopathogenesis. Trauma is considered as a contributing factor. Biopsy is the best approach for diagnosis and treatment. Although with no clear evidence, the application of topical corticosteroids improves lesion development and symptoms. (AU)

Oral manifestations in chikungunya patients: A systematic review.

BACKGROUND: Chikungunya fever is considered an abrupt onset arbovirus transmitted by mosquitoes, mainly Aedes aegypti and Aedes albopictus. The disease has a significant impact on the quality of life of affected persons, and many of its numerous symptoms have not yet been properly clarified, such as the manifestations that can occur in the oral cavity. The aim of this study was to identify the main oral manifestations related to chikungunya fever, as well as describe the demographic characteristics of patients, by conducting a systematic review of the literature. METHODS AND FINDINGS: Searches were performed in MEDLINE (PubMed), Embase (Elsevier), LILACS (VHL), Cochrane Library, Scopus, and CAPES electronic databases for theses and dissertations published up to January 16, 2021 without language and date restrictions. Additional manual searches of gray literature, reference list, and Google Scholar were carried out. We included 27 studies highlighting mainly oral manifestations that cause masticatory discomfort such as ulcers and oral thrush, gingival bleeding, pain and burning of the oral mucous membranes, temporomandibular joint (TMJ) arthralgia, opportunistic infections, and changes in taste. CONCLUSIONS: There seems to be a predominance of oral manifestations that cause discomfort when chewing, such as ulcerations in the acute phase of the disease, with complete remission within 3 to 10 days after the onset, apparently mostly affecting women and older persons. These oral manifestations can be compatible with basic viral infections related to inflammatory response and transitory immunosuppression.

EBV-positive Mucocutaneous Ulcer With Small Lymphocytic Infiltration Mimicking Nonspecific Ulceration.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorder may resemble nonspecific inflammation. We report 3 cases of immunosuppressed adult patients with small lymphocytic EBV ulcers in the skin and oral mucosa, characterized by a lack of atypical lymphocytic infiltration. All 3 cases were diagnosed in routine practice. For comparisons, cases of conventional Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) were reviewed which were extracted from our pathology archives (n=11). The present patients were 2 females and 1 male, aged above 70 years. The primary disease was rheumatoid arthritis (n=2) and dermatitis herpetiformis (n=1). The main source of immunosuppression was prednisolone (n=2) and methotrexate (n=1). The ulcers were located in the oral cavity, buttock, and/or external genitalia. Histology evaluation revealed nonspecific lymphocytic infiltration. Epstein-Barr virus-encoded small RNA (EBER)-positive cells were small and coexpressed CD20. The number of EBER-positive cells ranged from 52 to 132/HPF, which was within the range of that observed in the reviewed conventional EBVMCUs (range, 48 to 1328; median, 121). All 3 cases regressed spontaneously or by the reduction of immunosuppressants. Although the present cases lacked cytologic atypia, those clinical course and loads of EBER-positive cells (>50/HPF) suggested EBV involvement. Current cases of EBVMCU with small lymphocytic infiltration underscore the need for EBER in situ hybridization when an etiology of ulcer with predominant lymphocytes in an immunosuppressed patient is unclear.

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

Promising nanogels loaded with usnic acid for oral ulcer treatment: development, characterization, and in vivo evaluation in rabbits.

This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum nanogels. The characterization studies included physical, rheological, and bioadhesive properties as well as in vitro release and ex vivo studies. The rheological results revealed that the nanogels present pseudoplastic flow behavior. In vitro drug release showed a prolonged pattern. In further, the chosen UA nanogels showed very low percentages of penetration and permeation. F13, which showed the highest release, suitable bioadhesive properties (0.475 ± 0.033 N/cm2) and eligible particle size (250.22 ± 4.11 nm), PDI (0.089 ± 0.052), and zeta potential (20.56 ± 0.330 mV) values were chosen for in vivo experiments. The selected UA nanogels showed effective antimicrobial activity against Bacillus Cereus and great in vivo wound healing properties. The results indicated that suitable UA nanogels with desired properties could be prepared. The therapeutic potential of the nanogels for oral ulcers was assessed using an animal model and the histopathological findings suggested that the optimized formulation is a good choice for oral ulcer treatment. Nonetheless, further research is recommended to support its efficacy by applying pharmacodynamic and pharmacokinetic studies in human individuals.