Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Prospective Cohort Study Identifies Medical Predictors of Treatment-Related Oral Toxicities in Oral and Oropharyngeal Cancer Patients.

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.

Estimation of the in-plane ultimate stress of lamellar tissue as a function of bone mineral density and osteocyte lacunae porosity.

BACKGROUND AND OBJECTIVE: Detailed finite element models based on medical images (µ-CT) are commonly used to analyze the mechanical behavior of bone at microscale. In order to simulate the tissue failure onset, isotropic failure criteria of lamellar tissue are often used, despite its non-isotropic and heterogeneous nature. The main goal of the present work is to estimate the in-plane ultimate stress of lamellar bone, considering the influence of mineral content and the porosity due to the osteocyte lacunae concentration. METHODS: To this aim, a representative volume cell of lamellar tissue is modeled numerically, including: (1) non-isotropic elastic properties of tissue as a function of the bone mineral density and (2) explicit modeling of the osteocyte lacunae, considering the range of porosity content, size and orientation of ellipsoid-shaped lacunae. Firstly, the element size for the finite element models have been defined from a preliminary convergence analysis. Bounds on the ultimate stress of non-porous lamellar tissue are estimated for two values of bone mineral density, considering the results of tensile and compressive tests of wet osteons from the literature. Subsequently, the ultimate stress of lamellar tissue considering several values of micro-porosity is addressed. RESULTS: Results obtained in this work show that the strength of lamellar bone decreases exponentially with the increase of lacunae porosity concentration. Ultimate stress of non-porous tissue (p=0%) increases with high mineral content, reaching a value of S¯transc=355.40±39.80 MPa for compression in the transversal direction of the fiber bundles, being BMD=1.246g/cm3. The mean value for the longitudinal to transverse strength ratio evaluated for porosity p=0%,1% and 5% and a mineral content BMD=1.2g/cm3, is 2.47:1 for tension and 1.55:1 for compression. These values are in agreement with literature. CONCLUSIONS: Osteocyte lacunae act as stress concentrators, acting as potential stimulus for the bone regeneration process. A novel micromechanical model for the in-plane ultimate stress of lamellar tissue as a function of mineral content and lacunae concentration is presented. Additional considerations about the intralamellar shear stress evolution are also given.

The use of E-cigarettes as a risk factor for oral potentially malignant disorders and oral cancer: a rapid review of clinical evidence / El uso de cigarrillos electrónicos como factor de riesgo de trastornos orales potencialmente malignos y cáncer oral: una revisión rápida de la evidencia clínica

Background: The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens andyoung adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitroand in vivo studies have evidenced a variable quantity of potentially harmful components and some recognizedcarcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes mayplay active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapidreview aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentiallymalignant disorders (OPMD) and oral cancer.Material and Methods: A systematic search for English language articles published was performed in PubMed(MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelveclinical studies about OPMD and oral cancer risk in e-cigarette users.Results: The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes,DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However,results were inconsistent compared to tobacco smokers and control groups.Conclusions: the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes asa risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsiblyabout the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designedclinical studies are needed.(AU)

Lymphomas affecting the submandibular glands / Linfomas que afectan las glándulas submandibulares

Background: Lymphomas affecting the submandibular glands are very uncommon and few reports are currentlyavailable in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic fea-tures of an original series of lymphomas affecting the submandibular glands.Material and Methods: The pathology files of two institutions were searched for lymphoma cases affecting thesubmandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by apathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation,treatment, follow-up and status at last appointment were retrieved from the patients’ medical charts.Results: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with amean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma representedthe most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patientsdied, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma.Conclusions: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other sub-types may also be rarely diagnosed in this salivary gland.(AU)

Malignant tumors affecting the head and neck region in ancient times: Comprehensive study of the CRAB Database.

In the modern world, cancer is a growing cause of mortality, but archeological studies have shown that it is not exclusive to modern populations. The aim of this study is to examine the epidemiologic, social, and clinicopathologic features of head and neck cancers in ancient populations. To do this, we extracted all records that described malignant lesions in the head and neck region available in the Cancer Research in Ancient Bodies Database (CRAB). The estimated age, sex, physical condition of the remains (skeletonized, mummified), anatomic location of tumors, geographic location, chronology, tumor type, and methods of tumor diagnosis were collected. One hundred and sixty-seven cases were found, mostly originating from Europe (51.5%). Most records were of adults between 35 and 49 years of age (37.7%). The most involved site was the skullcap (60.4%), and the most common malignancies were metastases to the bone (65.3%) and multiple myeloma (17.4%). No primary soft tissue malignancies were registered. The results of our study indicate that head and neck cancers were present in ancient civilizations, at least since 500,000 BCE. The available data can help to improve the current understanding of the global distribution of head and neck cancer and its multidimensional impacts on populations in the contemporary world.

COVID-19 epidemic in Panama.

Objective: It is necessary to establish the evolution that the pandemic has had in Panama by weeks and months and to clearly establish the existence of surges or peaks, according to cases and deaths and the relationship with age groups. Methodology: We conducted a retrospective cohort study of all confirmed COVID-19 cases reported by the Ministry of Health of Panama during the first 3 years of the epidemic (March 9, 2020, March 11, 2023). All cases were obtained from information provided by the Ministry of Health. We obtained daily information of the population at the national level reported as new cases, deaths, admission to hospitals, admission to intensive care units and by age groups. The information is classified by epidemiological week and by month from the diagnosis of the first case until March 2023. Results: During the three years of the study, 1,032,316 cases of COVID-19 were registered in the Republic of Panama, and the number of deaths reported was 8,621, for a fatality rate of 0.83 % throughout that period. The number of deaths decreased over the 3 years of the pandemic; however, similar to the cases, there were periods of surges (peaks) per year in June/July and in December/January. The lethality progressively increased according to the age of the affected patients. During the first year, the lethality in those under 20 years of age was 0.05 %, and in those over 80 years old, it was 17.54 %. This pattern was maintained during the second year; however, there was a large decrease in all age groups. Conclusion: the highest lethality rate in Panama occurred in the first year of the pandemic, with a great decrease in the third year; the impact of lethality is proportional to the age of the individual, with a high possibility of death in those over 80 years of age. During each pandemic year, there are two peaks (surges of new cases and deaths) per year, which are important times to take into account to generate strategies aimed at reducing the impact.

DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

Medication-related osteonecrosis in torus palatinus: Report of a case and literature review.

BACKGROUND: Medication-related osteonecrosis of the jaw bones have been frequently reported. However, its occurrence in torus palatinus is very rare with only 10 cases published in the English-language literature. CASE REPORT: We describe an additional case in a 79-year-old woman, who was referred for evaluation of a painful swelling with areas of suppuration on the hard palate. CONCLUSION: Conservative treatment was performed and after spontaneous sequestrectomy, total healing was achieved.

Extracavitary Primary Effusion Lymphoma Affecting the Oral Cavity: A Rare Case Report.

Primary effusion lymphoma (PEL) is an aggressive neoplasm often diagnosed in immunosuppressed patients demonstrating peritoneal, pleural, or pericardial effusions. This high-grade lymphoma is strongly associated with human herpesvirus 8 (HHV8) infection and most of the lesions also show the presence of Epstein-Barr virus in tumor cells, which lacks CD20 expression and reveals a plasmablastic morphology and phenotype. The extracavitary or solid variant of PEL is even rarer and usually affects the lymph nodes and is currently considered a clinical manifestation of the classic PEL. In the oral cavity, extracavitary PEL is extremely rare and only a few patients have been previously reported, with no detailed clinicopathological description. The recognition of oral extracavitary PEL is even more important given the occurrence of plasmablastic lymphoma in the oral mucosa, which shares many clinical, microscopic, and phenotypic features with PEL, therefore, demanding from pathologists the search for HHV8, especially in immunosuppressed patients, and an appropriate clinical evaluation. In this report, we aim to describe a very rare extracavitary PEL affecting the palate of a 36-year-old patient and to review the literature regarding the extracavitary presentation of this aggressive lymphoma. This report demonstrates the importance of searching for HHV8 infection in oral lymphomas with plasmablastic features.

Reported physical examination methods for screening of oral cancer and oral potentially malignant disorders: a systematic review.

OBJECTIVE: This systematic review aimed to describe the method followed during physical examination and the anatomical structures of the head and neck assessed in screening for oral cancer and oral potentially malignant disorders (OPMDs). STUDY DESIGN: An extensive literature search was carried out using MEDLINE/PubMed, EMBASE, Scopus, LILACS, Web of Science, Cochrane databases, and gray literature. The risk of bias was available in all papers included. RESULTS: Of 9,688 records identified, 27 were included in this review, reporting data from 356,250 individuals screened and distributed across 11 countries. Most of these (n = 19) were based on 1 round of screening conducted by a dental professional or other health care workers. Most screening programs included visual inspection and palpation of the lips, oral cavity, and the most visible oropharyngeal sites, but the descriptions reported were imprecise. Additional inspection and palpation of the neck (submental, submandibular, cervical, and supraclavicular regions) to assess for the presence of swellings and any palpable neck nodes were also performed in 15 programs. CONCLUSION: In conclusion, there was considerable heterogeneity in the method of physical examination in screening programs for oral cancer and OPMDs among the included studies.

Prevalence and clinical characteristics of oral lesions in heart transplant patients induced by sirolimus and everolimus: a systematic review and meta-analysis on a global scale.

OBJECTIVE: Sirolimus (SRL) and everolimus (EVL) are increasingly included in immunosuppressive protocols after heart transplantation. They present some side effects, including the appearance of painful lesions in the oral cavity. Therefore, this systematic review aimed to verify the global prevalence and clinical characteristics of oral lesions induced by SRL and EVL in heart transplant patients. STUDY DESIGN: A systematic review was performed using 5 main electronic databases (Medline/PubMed, SCOPUS, EMBASE, Web of Science, and LILACS), in addition to the gray literature. Studies were independently assessed by 2 reviewers based on established eligibility criteria. The risk of bias was assessed using the Joanna Briggs Institute appraisal tools, and the certainty of evidence was evaluated through GRADE assessment. RESULTS: Seventeen studies (860 patients) were included in the qualitative analysis. Of these, 11 studies were pooled in a meta-analysis of prevalence. The worldwide prevalence of oral lesions induced by SRL and EVL in heart transplant patients was 10.0%, and most lesions were described as ulcers >1.0 cm, related to significant pain. CONCLUSIONS: Oral lesions induced by SRL and/or EVL, although not very prevalent, have a relevant impact on patient's lives and the continuity of treatment.

Malignant tumors affecting the head and neck region in ancient times: Comprehensive study of the CRAB Database

Abstract In the modern world, cancer is a growing cause of mortality, but archeological studies have shown that it is not exclusive to modern populations. The aim of this study is to examine the epidemiologic, social, and clinicopathologic features of head and neck cancers in ancient populations. To do this, we extracted all records that described malignant lesions in the head and neck region available in the Cancer Research in Ancient Bodies Database (CRAB). The estimated age, sex, physical condition of the remains (skeletonized, mummified), anatomic location of tumors, geographic location, chronology, tumor type, and methods of tumor diagnosis were collected. One hundred and sixty-seven cases were found, mostly originating from Europe (51.5%). Most records were of adults between 35 and 49 years of age (37.7%). The most involved site was the skullcap (60.4%), and the most common malignancies were metastases to the bone (65.3%) and multiple myeloma (17.4%). No primary soft tissue malignancies were registered. The results of our study indicate that head and neck cancers were present in ancient civilizations, at least since 500,000 BCE. The available data can help to improve the current understanding of the global distribution of head and neck cancer and its multidimensional impacts on populations in the contemporary world.

Oral manifestations of amyloidosis and the diagnostic applicability of oral tissue biopsy.

BACKGROUND: Amyloidosis exhibits a variable spectrum of systemic signs and oral manifestations that can be difficult to diagnose. This study aimed to characterize the clinical, demographic, and microscopic features of amyloidosis in the oral cavity. METHODS: This collaborative study involved three Brazilian oral pathology centers and described cases with a confirmed diagnosis of amyloidosis on available oral tissue biopsies. Clinical data were obtained from medical records. H&E, Congo-red, and immunohistochemically stained slides were analyzed. RESULTS: Twenty-six oral biopsies from 23 individuals (65.2% males; mean age: 59.6 years) were included. Oral involvement was the first sign of the disease in 67.0% of cases. Two patients had no clinical manifestation in the oral mucosa, although the histological analysis confirmed amyloid deposition. Amyloid deposits were distributed in perivascular (88.0%), periacinar and periductal (80.0%), perineurial (80.0%), endoneurial (33.3%), perimuscular (88.2%), intramuscular (94.1%), and subepithelial (35.3%) sites as well as around fat cells (100.0%). Mild/moderate inflammation was found in 65.4% of cases and 23.1% had giant cells. CONCLUSIONS: Amyloid deposits were consistently found in oral tissues, exhibiting distinct deposition patterns. Oral biopsy is less invasive than internal organ biopsy and enables the reliable identification of amyloid deposits even in the absence of oral manifestations. These findings corroborate the relevance of oral biopsy for the diagnosis of amyloidosis.

Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.