RESUMO
AIMS: Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer. A3B-related mutations are identified through C-to-T/-G base substitutions in 5'-TCA/T motifs. Herein, we present immunohistochemical and genomic data supportive of a role for A3B in head/neck MMs. METHODS AND RESULTS: A3B protein levels were assessed in oral (n = 13) and sinonasal (n = 13) melanomas, and oral melanocytic nevi (n = 13) by immunohistochemistry using a custom rabbit α-A3B mAb (5210-87-13). Heterogeneous, selective-to-diffuse, nuclear only, A3B immunopositivity was observed in 12 of 13 (92.3%) oral melanomas (H-score range = 9-72, median = 40) and 8 of 13 (62%) sinonasal melanomas (H-score range = 1-110, median = 24). Two cases negative for A3B showed prominent cytoplasmic staining consistent with A3G. A3B protein levels were significantly higher in oral and sinonasal MMs than intraoral melanocytic nevi (P < 0.0001 and P = 0.0022, respectively), which were A3B-negative (H-score range = 1-8, median = 4). A3B levels, however, did not differ significantly between oral and sinonasal tumours (P > 0.99). NGS performed in 10 sinonasal MMs revealed missense NRAS mutations in 50% of the studied cases and one each KIT and HRAS mutations. Publicly available whole-genome sequencing (WGS) data disclosed that the number of C-to-T mutations and APOBEC3 enrichment score were markedly elevated in head/neck MMs (n = 2). CONCLUSION: The above data strongly indicate a possible role for the mutagenic enzyme A3B in head/neck melanomagenesis, but not benign melanocytic neoplasms.
Assuntos
Melanoma , Neoplasias Bucais , Nevo Pigmentado , Neoplasias dos Seios Paranasais , Animais , Humanos , Coelhos , Melanoma/patologia , Mutação , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Citidina Desaminase/genéticaRESUMO
OBJECTIVES: The role of Human papillomavirus (HPV) in the oral squamous cell carcinoma (OSCC) has not been completely elucidated. The purpose of the present study was to investigate the prevalence and localization of HPV-16 virus in OSCC and to correlate HPV-16 positivity and p16INK4A expression with the clinical and pathological features of OSCC. METHODS: The archives of Oral Pathology at the University of Florida, College of Dentistry were accessed for demographic, clinical, histopathological data, and slides of 114 OSCC patients. HPV-16 positivity of OSCC was evaluated by p16INK4A immunohistochemistry (IHC) and HPV-16 E6/E7mRNA by in situ hybridization (ISH). RESULTS: Out of 114 consecutive pathological slides of OSCC, 16 samples (14%) showed positivity for p16INK4A by IHC and 14 samples (12%) were positive for HPV-16 E6/E7mRNA ISH and the Positivity showed a significant correlation with the patients' age, alcohol consumption, and the degree of OSSC differentiation. The hard palate showed the highest positivity of p16INK4A IHC and HPV-16 mRNA ISH (38%, 36% respectively). CONCLUSION: HPV-16 is a significant factor in oral carcinogenesis. We recommend using p16INK4A as a surrogate marker for HPV detection in OSCC, which can be complemented by RNA ISH for the identification of HPV subtypes.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Papillomavirus Humano , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Papillomaviridae/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismoRESUMO
Oral lesions may be the initial or only manifestation of leukemia and can be the key to early diagnosis. The varied nature of presenting signs and dentists' general lack of familiarity with oral presentations makes diagnosis challenging. This retrospective review reports a series of cases of leukemia to familiarize dentists with the oral manifestations and facilitate earlier diagnosis or recognition of relapse of this life-threatening disease. Following institutional review board approval, the University of Florida Oral Pathology Biopsy Service archive from 1994 to 2018 was queried for all oral biopsies resulting in a diagnosis of leukemia. Cases with insufficient diagnostic information or extraoral manifestations were excluded. Demographic, clinical, and histologic findings were tabulated. Ten cases with 12 biopsy sites were identified. Men (n = 6) were affected more commonly. The mean age of the patients was 58.4 years (range of 17 to 88 years). The gingiva was the most frequently biopsied site (n = 6; 50%). Importantly, 40% of the patients (n = 4) had no prior diagnosis of leukemia. A wide spectrum of clinical impressions was rendered, pyogenic granuloma being the most common, and the reported duration of lesions ranged from several weeks to 6 months. The rarity of patients presenting with leukemia may lead to low levels of clinical suspicion, misdiagnosis, and delays in treatment. However, oral lesions may be the first and only manifestation of leukemia, and clinicians should be aware of the clinical characteristics of these oral presentations to ensure early diagnosis and treatment, thereby helping to reduce disease-related morbidity and mortality.
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Leucemia , Úlceras Orais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Odontólogos , Gengiva/patologia , Humanos , Leucemia/complicações , Leucemia/diagnóstico , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Papel Profissional , Adulto JovemRESUMO
PURPOSE: Squamous odontogenic tumor (SOT) is a rare, benign, locally infiltrative odontogenic tumor of the gnathic bones. It is composed of islands of bland, well-differentiated squamous epithelium of varying shape and size. Because of histologic overlap, SOT has often been overdiagnosed as ameloblastoma and squamous cell carcinoma. It thus becomes important to understand the clinical, radiologic, histopathologic, and treatment characteristics of this tumor. MATERIALS AND METHODS: Using the PubMed and Google Scholar databases, we searched for reported cases of SOT published in the English-language literature. We were able to retrieve 49 acceptable cases and perform a comprehensive literature review of the intraosseous SOTs, with emphasis on their clinical, radiographic, and pathologic characteristics, as well as treatment strategies. In addition, we present an additional case of SOT affecting the posterior mandible in a 44-year-old female patient. RESULTS: The tumor in the posterior mandible in our patient was accompanied by acute pain and treated by enucleation. Histopathologic evaluation showed variably sized islands of benign squamous epithelium scattered in a fibrous stroma, consistent with the diagnosis of an SOT. Uneventful healing was noted at the 1-month postoperative appointment. However, the patient was lost to long-term follow-up. Our literature review showed that the average age at the time of diagnosis of SOT is 34.2 years. Men and women are equally affected, and the tumor does not show a predilection for either jaw bone. The most common locations are the anterior maxilla and posterior mandible. Most SOTs are treated conservatively by enucleation or curettage, whereas aggressive or recurrent tumors require radical resection. CONCLUSIONS: Careful evaluation of the excised specimen, with immunohistochemical investigations, may prove rewarding in differentiating an SOT from other odontogenic neoplasms and thus minimize the patient's chances of undergoing an unnecessary aggressive intervention.
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Ameloblastoma , Tumor Odontogênico Escamoso , Tumores Odontogênicos , Adulto , Tecido Conjuntivo , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Tumor Odontogênico Escamoso/diagnóstico por imagem , Tumor Odontogênico Escamoso/cirurgia , Tumores Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/cirurgiaRESUMO
INTRODUCTION: p16INK4a is a tumor suppressor protein that retards cell cycle progression from G1 to S phase. Prior studies have evaluated p16INK4a expression in odontogenic keratocyst and ameloblastoma, but data regarding other odontogenic cysts and tumors have been sparse. METHODS: With IRB approval, cases from the following entities were identified from archives of the UF Oral Pathology Biopsy Service (2005-2015): benign incidental odontogenic rest, dentigerous cyst, lateral periodontal cyst, calcifying odontogenic cyst, glandular odontogenic cyst, odontogenic keratocyst, orthokeratinized odontogenic cyst, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and ameloblastoma. All cases were submitted for p16INK4a immunohistochemical testing. RESULTS: Results were scored as follows: nuclear and cytoplasmic staining of <5% cells (score 0), 5%-25% (score 1), 25%-50% (score 2), >50% (score 3). No significant difference in p16INK4a staining was noted between odontogenic cysts and the listed odontogenic tumors (chi-square, P = .540). When comparing lesions with higher recurrence rates (over 25% as reported in the literature) versus lesions with low recurrence rates (under 25%), higher recurrence correlated to significantly higher p16INK4a positivity (chi-square, P = .001). Follow-up testing was performed on 18 cases with "2" or "3" p16INK4a expression scores for high-risk HPV strains through HPV in situ hybridization (ISH) messenger RNA testing with no cases exhibiting a positive result. CONCLUSION: This study exhibits an association between increased p16INK4a positivity and odontogenic lesions with higher recurrence rates and highlights the role of p16INK4a as a progression marker unrelated to HPV expression in this group of pathologic entities.
Assuntos
Ameloblastoma , Cisto Dentígero , Cistos Odontogênicos , Tumores Odontogênicos , Infecções por Papillomavirus , Humanos , Recidiva Local de NeoplasiaRESUMO
Background: Betel nut (areca) is the world's fourth most commonly used addictive substance. Arecoline, a muscarinic agonist in areca, is also a partial agonist for the addiction-related high-affinity brain nicotine receptors. In many countries, smokeless tobacco is commonly mixed with areca. Objective: We sought to evaluate the knowledge of self-harm, and addiction associated betel quid use in an unban population. Methods: We conducted a survey study of 200 betel quid users in Yangon, Myanmar, and a survey of betel quid vendors to determine the relative amounts of areca and tobacco in the available quids. Results: The data determined that a large majority of the survey subjects (84%) used tobacco with their areca. Users had a general awareness that betel chewing was "a bad habit" (85%) and 80% were aware of the cancer risks. Understanding areca addiction remains a challenge since, aside from the strong muscarinic activity of arecoline stimulating salivation, overt neurologic effects are difficult for even the users to identify. Fifty eight percent of the respondents indicated that chewing betel quid had effects like drinking coffee, and 55.5% indicated that it had effects like drinking alcohol. Data obtained from the quid vendors indicated that 75% added tobacco in equal amounts to areca. Conclusion: The concomitant use of nicotine and areca indicates that betel quid addiction includes a significant component of nicotine dependence. However, the additional activities of areca, including the muscarinic effects of arecoline, indicate that potential cessation therapies should optimally address other factors as well.
Assuntos
Areca , Tabagismo , Tabaco sem Fumaça , Humanos , Mianmar/epidemiologia , Tabagismo/epidemiologiaRESUMO
OBJECTIVES: Lichenoid granulomatous reaction can be subcategorized into lichenoid granulomatous dermatitis or lichenoid granulomatous stomatitis. It is described in the literature as demonstrating a band-like lichenoid infiltration with clusters of histiocytic or granuloma formation. In this study, we presented a large case series of lichenoid granulomatous stomatitis including demographics, histological features, and subcategories and compared findings with current literature. METHODS AND MATERIALS: We retrieved all cases diagnosed with lichenoid reaction with granulomatous inflammation between January 1, 2000, and August 1, 2016, from the University of Florida Oral Pathology Biopsy Service Archives. RESULTS: A total of 47 patients with tissue from 50 biopsy sites were included. The majority of the cases were noted in females (64%) with a mean age of 59 years (range 30-88). Most patients were Caucasian, and the most common sites in descending order were: gingiva, buccal mucosa, vestibule, tongue, lip, palate, and occasional multifocal involvement. Clinical impressions by the treating clinicians included leukoplakia, dysplasia, carcinoma in situ, squamous cell carcinoma, lichen planus, vesiculobullous disease, trauma, and allergy. The histologic features of these cases ranged from lichenoid mucositis with numerous aggregates of histiocytes to well-formed granulomas, in accordance with previous classifications of similar dermatologic lesions. All cases revealed positive CD 68 in the histiocytic infiltrates and were negative for microorganisms utilizing acid-fast bacilli, Grocott methenamine-silver, and periodic acid-Schiff stains. CONCLUSION: Lichenoid granulomatous disease may be more common than previously reported; however, its etiology remains unknown and patients should be kept under long-term clinical follow-up.
Assuntos
Líquen Plano Bucal , Erupções Liquenoides , Estomatite , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal , Estudos RetrospectivosRESUMO
PURPOSE: To describe and discuss the demographic and clinical features of oral melanomas, which are relatively rare but deadly neoplasms, and list the criteria for their diagnosis to increase early detection. MATERIALS AND METHODS: An institutional review board-approved retrospective search of oral melanomas was performed in the archives of the University of Florida Oral and Maxillofacial Pathology Biopsy Service (Gainesville, FL) from 2015 through 2018. Exclusion criteria included cases with inconclusive diagnosis, skin involvement, and missing clinical data or slide material. Of 7 patients with a diagnosis of melanoma of the head and neck region, 6 (87.5%) were found to be diagnosed with oral melanomas and met the inclusion criteria. RESULTS: All 6 patients were at least 45 years (range, 45 to 87 yr). The male-to-female ratio was 4:2. Three patients were asymptomatic and 3 experienced symptoms, including pain, swelling, and tingling. Seven lesions were detected in these 6 patients. Three of these lesions were located on the maxillary gingiva, 2 were on the mandibular gingiva, and 2 involved the palate. Two lesions were diagnosed as spindle cell melanoma, 4 were diagnosed as melanoma, and 1 was diagnosed as a mucosal lentiginous melanoma. CONCLUSION: Oral melanomas should be considered in the differential diagnosis of oral pigmented lesions, especially on the gingiva or palate, in middle-age and elderly patients. Oral melanomas have a male bias. In addition, supportive criteria enabling early diagnosis of oral melanomas is addressed.
Assuntos
Melanoma , Neoplasias Bucais , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/cirurgia , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/cirurgia , Palato , Estudos RetrospectivosRESUMO
Bisphosphonates have been implicated in the induction of medication-related osteonecrosis of the jaw (MRONJ) since 2004. Since then, the spectrum of drugs implicated in the onset of MRONJ has broadened to include other antiresorptive and antiangiogenic drugs. Denosumab is an antiresorptive drug that has been on the market since 2010. Denosumab inhibits osteoclast formation, function, and survival and increases bone mineral density. As a result, denosumab is indicated for the treatment of osteoporosis and bone metastases. This article reports 2 cases of MRONJ associated with denosumab use. The characteristics and progression of MRONJ in patients who take denosumab are reviewed, and therapeutic measures are discussed.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Denosumab/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos , Humanos , OsteoporoseRESUMO
PURPOSE: Peripheral ameloblastoma (PA) is a rare odontogenic tumor arising in the mucosa of tooth-bearing areas of the jaws that typically shows no radiographic evidence of bone involvement. It bears close histologic resemblance to intraoral basal cell carcinoma (IOBCC), an extremely rare entity. In our experience from previous published data, 3 cases of IOBCC were initially misdiagnosed as PA and were later differentiated from PA on the basis of Ber-EP4 protein expression. This unusual but significant experience set the premise for us to rule out a diagnosis of IOBCC by evaluating Ber-EP4 expression in all previously diagnosed cases of PA from the University of Florida Oral Pathology (UFOP) biopsy service archives. MATERIALS AND METHODS: With institutional review board approval, 18 cases of PA were retrieved from the UFOP biopsy service archives. We describe the clinicopathologic features of these cases and discuss the Ber-EP4 immunohistochemical staining performed to rule out a potential diagnosis of IOBCC. In addition, we conducted calretinin and epithelial membrane antigen staining for 1 case of PA. RESULTS: Most PAs presented in the lingual gingiva of the posterior mandible. Men were affected twice as often as women, and the average age at the diagnosis was 59 ± 21.5 years. Of the 18 lesions, 13 showed no reactivity to Ber-EP4, 4 displayed patchy membranous immunoreactivity, and 1 demonstrated nonspecific reactivity. CONCLUSIONS: We have concluded that all cases of PA that present with histologic overlap with basal cell carcinoma, especially those from incisional biopsies, those that appear significantly infiltrative, and those that appear ulcerated and/or demonstrate recurrence should be evaluated with Ber-EP4 to rule out IOBCC.
Assuntos
Ameloblastoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/diagnóstico , Neoplasias Maxilomandibulares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ameloblastoma/metabolismo , Ameloblastoma/patologia , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Burning mouth syndrome (BMS) is a complex condition that affects the oral cavity, and data regarding effective treatment are limited. The purpose of this study was to explore the demographic and clinical information along with treatment outcomes for patients with BMS treated in a large referral center. Clinical records of the Oral Medicine Clinic at the University of Florida College of Dentistry were retrospectively searched for patients diagnosed between 2009 and 2014. Clinical data and treatment effectiveness were recorded. The records of 64 patients were included in this study. Women represented the majority of patients (81.2%), and the average age of all patients was 65 years. The most common systemic diseases were hypertension (59.4%), psycho-logical disorders (51.6%), and gastroesophageal reflux disease (50.0%). The majority of patients were taking 5 or more medications (70.3%). Treatment frequency and efficacy were as follows: a-lipoic acid, 47.5% frequency (57 prescribed treatments of 120 total treatments) and lasting improvement reported with 45.6% of prescribed treatments; clonazepam, 17.5% frequency (21/120) and improvement reported with 33.0% of prescribed treatments; oral disintegrating clonazepam, 15.8% frequency (19/120) and improvement reported with 52.6% of prescribed treatments; and topical vitamin E, 5.0% frequency (6/120) and improvement reported with 33.0% of prescribed treatments. Chi-square analysis indicated that a significantly better response to treatment was reported by women (P = 0.010) and patients who reported involvement limited to the tongue rather than multifocal oral involvement (P = 0.040); however, the significant relationships did not persist when the variables were evaluated together using logistic regression analysis. No other clinical or demographic features showed significant differences in response to treatment. Although treatment effectiveness in this study was variable and limited for some regimens due to infrequent usage, many of the patients reported alleviation of symptoms.
Assuntos
Síndrome da Ardência Bucal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome da Ardência Bucal/diagnóstico , Síndrome da Ardência Bucal/tratamento farmacológico , Síndrome da Ardência Bucal/etiologia , Clonazepam/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ácido Tióctico/uso terapêutico , Resultado do Tratamento , Vitamina E/uso terapêuticoRESUMO
Several medications have been reported as possible etiologic factors for oral lichen planus (OLP) and oral lichenoid lesions (OLLs). This study investigated the medication profile and medical history of patients with biopsy-proven OLP or OLLs, also classified by the clinically nonspecific term oral lichenoid mucositis (OLM), in a busy oral medicine clinic. The University of Florida College of Dentistry records from 2009 to 2014 were searched retrospectively for all patients with a biopsy-proven diagnosis of OLP, OLLs, or OLM. Patients were excluded if dysplasia or carcinoma was diagnosed concurrently at the same biopsy site. The demographics, clinical parameters, systemic diseases, histologic diagnosis, and direct immunofluorescence testing results were recorded. Medication category use was recorded based on both commonly used medications and those that have been reportedly linked to lichenoid disease in the literature. A total of 155 patients with an average age of 63.6 years were included. The majority of patients were women (76.8%) and Caucasian (91.8%). Most of the lesions were multifocal and mixed (white-red) in appearance. The most common systemic conditions were hypertension (n = 80; 51.6%) followed by thyroid disease (n = 52; 33.5%) and diabetes (n = 26; 16.8%). Antihypertensives were the most common medication category followed by, in descending order, nonsteroidal anti-inflammatory drugs, cholesterol-lowering medications, psychiatric medications, and thyroid replacement drugs. The records revealed that 87.7% of the patients took at least 1 medication from 1 of the categories studied. Medication use is common in patients with biopsy-proven OLP or OLLs. Although causation cannot be assessed from the results of this study, the clinician should consider the possibility of medication as a complicating factor in patients with OLP or OLLs.
Assuntos
Líquen Plano Bucal/induzido quimicamente , Mucosite/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Comorbidade , Feminino , Humanos , Líquen Plano Bucal/diagnóstico , Masculino , Anamnese , Pessoa de Meia-Idade , Mucosite/diagnóstico , Polimedicação , Estudos Retrospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Saliva functions in innate immunity of the oral cavity, protecting against demineralization of teeth (i.e. dental caries), a highly prevalent infectious disease associated with Streptococcus mutans, a pathogen also linked to endocarditis and atheromatous plaques. Gel-forming mucins are a major constituent of saliva. Because Muc19 is the dominant salivary gel-forming mucin in mice, we studied Muc19(-/-) mice for changes in innate immune functions of saliva in interactions with S. mutans. When challenged with S. mutans and a cariogenic diet, total smooth and sulcal surface lesions are more than 2- and 1.6-fold higher in Muc19(-/-) mice compared with wild type, whereas the severity of lesions are up to 6- and 10-fold higher, respectively. Furthermore, the oral microbiota of Muc19(-/-) mice display higher levels of indigenous streptococci. Results emphasize the importance of a single salivary constituent in the innate immune functions of saliva. In vitro studies of S. mutans and Muc19 interactions (i.e. adherence, aggregation, and biofilm formation) demonstrate Muc19 poorly aggregates S. mutans. Nonetheless, aggregation is enhanced upon adding Muc19 to saliva from Muc19(-/-) mice, indicating Muc19 assists in bacterial clearance through formation of heterotypic complexes with salivary constituents that bind S. mutans, thus representing a novel innate immune function for salivary gel-forming mucins. In humans, expression of salivary MUC19 is unclear. We find MUC19 transcripts in salivary glands of seven subjects and demonstrate MUC19 glycoproteins in glandular mucous cells and saliva. Similarities and differences between mice and humans in the expression and functions of salivary gel-forming mucins are discussed.
Assuntos
Cárie Dentária/metabolismo , Cárie Dentária/microbiologia , Imunidade Inata/fisiologia , Mucinas/metabolismo , Saliva/metabolismo , Streptococcus mutans/patogenicidade , Adulto , Animais , Cárie Dentária/imunologia , Feminino , Humanos , Imunidade Inata/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Mucinas/genéticaRESUMO
Treponema denticola is a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between periodontal disease induced by chronic oral T. denticola infection and atherosclerosis in hyperlipidemic ApoE(-/-) mice. ApoE(-/-) mice (n = 24) were orally infected with T. denticola ATCC 35404 and were euthanized after 12 and 24 weeks. T. denticola genomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P = 0.0172) higher IgG antibody levels and enhanced intrabony defects than sham infection. T. denticola-infected mice had higher levels of horizontal alveolar bone resorption than sham-infected mice and an associated significant increase in aortic plaque area (P ≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared to those of sham-infected mice. T. denticola infection altered the expression of genes known to be involved in atherosclerotic development, including the leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescent in situ hybridization (FISH) revealed T. denticola clusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronic T. denticola periodontal infection and vascular atherosclerosis in vivo in hyperlipidemic ApoE(-/-) mice. T. denticola is closely associated with periodontal disease and the rapid progression of atheroma in ApoE(-/-) mice. These studies confirm a causal link for active oral T. denticola infection with both atheroma and periodontal disease.
Assuntos
Aorta/microbiologia , Apolipoproteínas E/metabolismo , Aterosclerose/etiologia , Infecções por Bactérias Gram-Negativas/complicações , Doenças Periodontais/etiologia , Treponema denticola/fisiologia , Animais , Anticorpos Antibacterianos/sangue , Apolipoproteínas E/genética , Aterosclerose/microbiologia , Reabsorção Óssea/microbiologia , Gengivite/complicações , Gengivite/microbiologia , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Knockout , Doenças Periodontais/microbiologia , Fatores de RiscoRESUMO
OBJECTIVE: Oral plasma cell mucositis (PCM) or localized plasma cell gingivitis (PCG) is an idiopathic inflammatory condition often associated with hypersensitivity reactions. This study aimed to evaluate the frequency and features of PCM/PCG in a large biopsy service over a time period of more than 20 years. STUDY DESIGN: The biopsy archives at University of Florida College of Dentistry were searched from 2000 through the first quarter of 2023 for cases of oral PCM or PCG. Case data were aggregated and analyzed. RESULTS: A total of 107 cases were included. Between 2000 and 2019, PCM/PCG was diagnosed in 0.03% of all biopsy cases. Starting in 2020 through 2023, the percentage of biopsies diagnosed as PCM/PCG increased threefold to 0.10% of all biopsy cases, and the mean patient age increased by 3 years. There were no statistically significant differences between cases diagnosed from 2000 to 2019 and those from 2020 to 2023 regarding age, sex, location, or histology. CONCLUSIONS: A significant increase in PCM/PCG was identified in this study at one institution coinciding with the start of the COVID-19 pandemic. Further investigation is recommended to determine if this is a widespread phenomenon and identify possible etiologic mechanisms.
Assuntos
COVID-19 , Gengivite , Mucosite , Estomatite , Humanos , COVID-19/epidemiologia , Teste para COVID-19 , Gengivite/etiologia , Gengivite/patologia , Mucosite/patologia , Pandemias , Plasmócitos/patologia , Estudos Retrospectivos , Estomatite/etiologiaRESUMO
Juvenile ossifying fibroma (JOF) is an uncommon benign fibro-osseous lesion (BFOL) of the maxillofacial bones with a locally aggressive nature and a high recurrence rate. Murine Double Minute 2 (MDM2) is an oncogene located at chromosome 12 (12q13-15) that inhibits the tumor suppressor gene TP53. The presence of MDM2 gene locus amplification is a useful molecular adjunct in the evaluation of some sarcomas, including low-grade intramedullary osteosarcoma (LGIOS). JOF and LGIOS have some overlapping clinical and histopathological features. The aim of this study is to evaluate a series of JOF for the presence of MDM2 gene locus amplification using fluorescence in-situ hybridization (FISH). MATERIALS AND METHODS: With IRB approval, a search of the institutional files of the archives of the Oral Pathology and Surgical Pathology biopsy services at the University of Florida Health was performed. The cases were re-evaluated by an oral pathology resident, an oral and maxillofacial pathologist, and a bone and soft tissue pathologist. Cases with consensus in diagnosis were selected (n = 9) for MDM2 testing. Testing by FISH for MDM2 gene locus amplification was applied to all retrieved cases. RESULTS: The examined cases were all negative for MDM2 gene locus amplification via FISH testing. CONCLUSION: In our small series, JOF did not demonstrate MDM2 gene locus abnormality, a characteristic of LGIOS. This finding suggests that JOF has a distinct underlying pathogenesis. If confirmed in a larger series, these findings may be useful in distinguishing these two entities in cases with overlapping features or when minimal biopsy material is available.
Assuntos
Fibroma Ossificante , Amplificação de Genes , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas c-mdm2 , Humanos , Proteínas Proto-Oncogênicas c-mdm2/genética , Fibroma Ossificante/genética , Fibroma Ossificante/patologia , Masculino , Feminino , Adolescente , Criança , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Pré-Escolar , Adulto JovemRESUMO
Childhood Sjögren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjögren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4+ T effector memory, and XCL1+ NK cells as potential key players in childhood Sjögren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children. A unique cluster of monocytes with type I and II IFN-related genes is identified in childhood Sjögren's disease, compared to the age-matched control. In vitro regulatory T cell functional assay demonstrates intact functionality in childhood Sjögren's disease in contrast to reduced suppression in adult Sjögren's disease. Mapping this transcriptomic landscape and interplay of immune cell subsets will expedite the understanding of childhood Sjögren's disease pathogenesis and set the foundation for precision medicine.
Assuntos
Síndrome de Sjogren , Adulto , Criança , Humanos , Pré-Escolar , Síndrome de Sjogren/genética , Síndrome de Sjogren/diagnóstico , Linfócitos T Reguladores , Perfilação da Expressão Gênica , Transcriptoma , Células Matadoras NaturaisRESUMO
BACKGROUND: Childhood Sjögren's disease is a rare, underdiagnosed, and poorly-understood condition. By integrating machine learning models on a paediatric cohort in the USA, we aimed to develop a novel system (the Florida Scoring System) for stratifying symptomatic paediatric patients with suspected Sjögren's disease. METHODS: This cross-sectional study was done in symptomatic patients who visited the Department of Pediatric Rheumatology at the University of Florida, FL, USA. Eligible patients were younger than 18 years or had symptom onset before 18 years of age. Patients with confirmed diagnosis of another autoimmune condition or infection with a clear aetiological microorganism were excluded. Eligible patients underwent comprehensive examinations to rule out or diagnose childhood Sjögren's disease. We used latent class analysis with clinical and laboratory variables to detect heterogeneous patient classes. Machine learning models, including random forest, gradient-boosted decision tree, partial least square discriminatory analysis, least absolute shrinkage and selection operator-penalised ordinal regression, artificial neural network, and super learner were used to predict patient classes and rank the importance of variables. Causal graph learning selected key features to build the final Florida Scoring System. The predictors for all models were the clinical and laboratory variables and the outcome was the definition of patient classes. FINDINGS: Between Jan 16, 2018, and April 28, 2022, we screened 448 patients for inclusion. After excluding 205 patients due to symptom onset later than 18 years of age, we recruited 243 patients into our cohort. 26 patients were excluded because of confirmed diagnosis of a disorder other than Sjögren's disease, and 217 patients were included in the final analysis. Median age at diagnosis was 15 years (IQR 11-17). 155 (72%) of 216 patients were female and 61 (28%) were male, 167 (79%) of 212 were White, and 20 (9%) of 213 were Hispanic, Latino, or Spanish. The latent class analysis identified three distinct patient classes: class I (dryness dominant with positive tests, n=27), class II (high symptoms with negative tests, n=98), and class III (low symptoms with negative tests, n=92). Machine learning models accurately predicted patient class and ranked variable importance consistently. The causal graphical model discovered key features for constructing the Florida Scoring System. INTERPRETATION: The Florida Scoring System is a paediatrician-friendly tool that can be used to assist classification and long-term monitoring of suspected childhood Sjögren's disease. The resulting stratification has important implications for clinical management, trial design, and pathobiological research. We found a highly symptomatic patient group with negative serology and diagnostic profiles, which warrants clinical attention. We further revealed that salivary gland ultrasonography can be a non-invasive alternative to minor salivary gland biopsy in children. The Florida Scoring System requires validation in larger prospective paediatric cohorts. FUNDING: National Institute of Dental and Craniofacial Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Heart, Lung, and Blood Institute, and Sjögren's Foundation.
Assuntos
Aprendizado de Máquina , Síndrome de Sjogren , Humanos , Estudos Transversais , Criança , Feminino , Masculino , Adolescente , Síndrome de Sjogren/diagnóstico , Índice de Gravidade de Doença , Florida/epidemiologiaRESUMO
BACKGROUND: Intraosseous xanthomas are rare benign lesions sometimes associated with excess lipid production. Xanthoma of the jaw bones (XJB) was first reported in 1964, and fewer than 50 cases have been reported in the English literature to date. The etiopathogenesis of XJB is highly suggestive of a reactive process or a metabolic condition. METHOD: Seven cases of XJBs were retrieved from the archives of 4 oral and maxillofacial pathology services. Clinical, radiographic and histopathologic features of all these cases were retrospectively analyzed. Immunohistochemical (IHC) stains for S100 and CD68 were performed. RESULTS: All seven cases involved the mandible. Patients' age ranged between 13 and 69 years with an evenly distributed female to male ratio. One patient had a medical history of hyperlipidemia, but the medical and dental histories of the others were unremarkable. For most cases, XJB was an incidental finding discovered during routine radiographic examination. Swelling and cortical expansion were noted in a few cases. Radiographically, cases typically presented as either well-defined multilocular or unilocular lesions, which were either radiolucent or mixed radiolucent/radiopaque. All the lesions were treated with surgical curettage and no recurrence was observed during subsequent follow-ups. Each of the seven cases exhibited sheets of foamy macrophages. The diagnosis is established by exclusion of entities with overlapping microscopic features and involved correlation with the clinical, histological, radiographic and IHC profiles. Immunohistochemically, all the cases expressed diffuse positivity for CD68 and were negative for S100. CONCLUSION: XJB is a rare lesion of unknown etiology, which may mimic other benign or reactive jaw lesions. Due to its rarity and the potential diagnostic challenges it presents, clinicians must remain vigilant and consider CXJ in their differential when assessing radiolucent jaw anomalies.