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Post-mortem samples of parotid gland were obtained from 15 patients with a history of diabetes mellitus for a minimum of 5 years, and from 15 age- and sexmatched controls. The tissue was studied by direct immunofluorescence for abnormal binding of selected serum proteins, including IgG, IgM, IgA, C[SUB3], fibrinogen, polyvalent immunoglobulin and albumin, to acinar and ductal basement membranes of the gland. Thickness of these basement membranes was also assessed using a calibrated magnifier on uniformly enlarged photomicrographs of the tissue which had been stained by the chromotrope silver methenamine method to highlight basement membranes. Results of this investigation revealed parotid gland basement membrane abnormalities in all diabetic subjects as indicated by the binding of IgG, albumin and polyvalent immunoglobulins to ductal and acinar basement membranes. These basement membranes were uniformly negative in control subjects for the binding of all serum proteins tested. Binding of IgA was also noted in 7 of 15 experimental subjects, with 6 of these representing Type I diabetics. Basement membrane measurements revealed no difference in thickness between diabetic and non-diabetic subjects. Variations in parotid diabetic basement membranes evidenced in this study further substantiate the idea that membranopathy in this disease is systemic in nature. [ABSTRACT FROM AUTHOR]

Background: Report of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA., Methods: A 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms., Results: A total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency., Conclusion: Our findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flores-Hidalgo, Bankhead, Murrah and Padilla.)

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing data-sets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS-CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection and implicates saliva in viral transmission.

Objective: The aim of this study was to identify the type and distribution of CD4+ and CD8+ T lymphocytes in oral mucosal specimens to potentially distinguish between underlying alterations or patterns in oral epithelial dysplasia and oral lichen planus., Study Design: This pilot study included 10 archived tissue samples that were received at the University of North Carolina Oral and Maxillofacial Pathology Laboratory and were diagnosed as oral lichen planus and moderate to severe epithelial dysplasia. Dual staining with CD4 and CD8 antibodies was carried out on each case. Slides were scanned in the Aperio ScanScope FL (Leica Biosystems, Wetzlar, Germany) and archived. Histomorphometric analysis was performed to detect inflammatory cells expressing CD4 and CD8 biomarkers in the epithelial and connective tissue regions., Results: No differences were found in the amount and ratio of CD4+/CD8+ lymphocytes among the 3 groups analyzed; however, the intraepithelial CD8+ lymphocyte distribution was strikingly different between lichen planus and moderate to severe epithelial dysplasia., Conclusions: The localization of CD8+ cells can be potentially useful as an adjunctive diagnostic procedure to distinguish oral epithelial dysplasia from other inflammatory entities, such as lichen planus., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: We report here the 10-year experience with oral hairy leukoplakia (OHL) at the Division of Oral and Maxillofacial Pathology at the University of North Carolina at Chapel Hill, NC, USA., Study Design: All the associated hematoxylin and eosin and Epstein-Barr virus encoding region in situ hybridization slides of OHL cases between January 1, 2008, and February 1, 2017, were retrieved and reviewed. Collected demographic characteristics, clinical presentation, medical and social histories were reviewed and reported., Results: Six OHL cases with confirmed in situ hybridization showed predilection for the lateral tongue. The study included 3 females and 3 males (mean age 50.5 years; age range 29-70 years). One patient had known HIV-positive status before biopsy was performed. Three patients had reported a history of heavy smoking. Other medical conditions reported were history of breast cancer, a long history of corticosteroid inhaler use for asthma treatment, high cholesterol, diabetes, and hypertension., Conclusions: The findings of this study indicate the need to include OHL as a potential entity in the differential diagnosis of leukoplakic tongue lesions, regardless of the patient's HIV status. In addition, the presence of OHL in the patient requires investigation of various explanations for EBV infection, including immunosuppression caused by HIV infection or chronic steroid use., (Published by Elsevier Inc.)

Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50-80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human "dentome") for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment.

Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues ("dentome"). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the "dentome" and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value.

This study investigated the effect of topical antibiotic treatment on pulp revascularization in replanted teeth. Thirty-four immature teeth were selected from three young dogs. Baseline radiographs and laser Doppler flowmetry (LDF) readings were obtained. Specimens were randomly divided into four groups: Thirty-eight teeth were extracted, kept dry for 5 min, and either (Group 1) covered with minocycline mixture (G1, n = 11), (Group 2) soaked in doxycycline (G2, n = 11), or (Group 3) soaked in saline (G3-negative control, n = 6), and replanted. Teeth in Group 4 were not extracted (positive control, n = 6). Postoperative radiographs and LDF readings were obtained for 2 months after replantation. After sacrifice, the jaws were collected and processed for light microscopy. Pre- and postreplantation LDF readings and radiographs, and histologic findings were analyzed to assess revascularization. Pulp revascularization occurred in 91% (G1), 73% (G2), and 33% (G3) of the specimens. In conclusion, minocycline facilitates pulp revascularization in replanted immature teeth after replantation., (Copyright Blackwell Munksgaard, 2004.)

Objectives: Differentiating polymorphous low-grade adenocarcinoma (PLGA) from pleomorphic adenoma (PA) in salivary gland biopsy specimens from the palatal region might be a diagnostic dilemma for the pathologist when tumors are cellular with minimal matrix material. Glial fibrillary acidic protein (GFAP), expressed by a number of cells in the mature central nervous system, is also expressed in tumors not generally considered to be of glial origin. PAs have previously been reported to strongly express GFAP. PLGAs have been examined for the expression of this protein only in small group studies with variable results. The objective of this study was to determine whether differential expression of GFAP in these 2 tumors could be diagnostically significant., Study Design: A total of 42 PLGAs and 36 PAs, formalin-fixed and paraffin-embedded, were immunostained with rabbit polyclonal antibodies to GFAP. CNS tissue was used as a positive control., Results: Results showed the 36 cases of PA to be strongly positive for GFAP. Of PLGAs, 31 were negative and 11 showed faint patchy reactivity in luminal cells., Conclusions: The results strongly support a role for GFAP as a diagnostic adjunct in the microscopic differential diagnosis of PLGA versus PA. This study is the largest investigation with consistent results to date addressing the application of this antibody to the diagnostic problem of PA versus PLGA.

Objective: To develop a human oral epithelial cell line to constitute a continuous source of cells readily available for human oral epithelial cell research., Study Design: Oral epithelial cells from a 30-week gestational, stillborn male fetus were grown in serum-free medium and transfected by lipid-mediation with the shuttle vector plasmid, pZ189, containing the T-antigen coding region and replication origin from the SV40 virus., Results: Resulting cultures produced foci of rapidly multiplying cells that failed to senesce, in contrast to controls. The transformed culture, designated GMSM-K, was polyclonal. The original culture possessed a normal human male karyotype, and the transformed line was largely hypotetraploid. Multiple clones, isolated from soft agar studies and low density plating, showed decreased doubling times. Electron microscopy and immunohistochemistry confirmed an epithelial phenotype. Cells did not generate tumors in nude mice., Conclusion: Few human epithelial cell lines are available to investigators and most are tumor-derived. The nontumor-derived GMSM-K line has value as a resource for human oral epithelial cell research.

Adenomatoid odontogenic tumor commonly occurs in association with the crowns of unerupted teeth. An extrafollicular variant, radiographically in relationship to root apices, has been reported. However, clear association with the root apices at surgery has not been demonstrated. We report a case of adenomatoid odontogenic tumor in the anterior mandible in a 21-year-old woman that presented radiographically at the root apices and at surgery as a radicular cyst. We believe this represents the first reported case of adenomatoid odontogenic tumor presenting as periapical disease both clinically and radiographically. The diagnosis of adenomatoid odontogenic tumor should be considered when the clinician is presented with a corticated radiolucency in the anterior jaw, especially in teens and young adults.

Oral lichen planus is one of the most common mucosal diseases that require management by the dental practitioner. The gingival presentation of this disease can be particularly problematic. Accurate diagnosis is of paramount importance for effective management, and tissue specimens are often required to distinguish this disease from other vesiculo-ulcerative diseases. The lichen planus patient can generally be managed with topical steroids. The use of antibiotics may be an important adjunctive consideration for patients with a concurrent significant periodontal condition. The possibility of carcinoma arising in lichen planus lesions is addressed. The learning objective of this article is to define specific parameters that contribute to the definitive diagnosis in order to promote objective, rather than empirical, treatment and to delineate specific points to address in patient education.

We report the apparent first case of a trichilemmal cyst presenting intraorally. Trichilemmal cysts are cysts of epithelial origin with a distinctive keratinization pattern that simulates that of the human anagen hair follicle between bulge and sebaceous gland and in the sac surrounding catagen hairs. This type of keratinization of outer root sheath epithelium occurs when it is freed from its internal cover of inner root sheath. This particular case showed evidence of mild epithelial proliferation and slight foci of "metaplastic" epidermoid keratinization, possibly related to mild trauma. The rarity of intraoral hairs undoubtedly accounts for the lack of reported cases of trichilemmal cysts in oral or perioral locations.

High prevalence of both tobacco use and latent herpes simplex virus type 1 suggests the opportunity for synergism between these agents as cocarcinogens. In this study, postprimary human oral epithelial cell cultures were infected with herpes simplex virus type 1 pretreated with 2% extracts of either loose leaf, moist, or dry snuffs. Cultures were subsequently periodically exposed to the tobacco. Parameters measured included percentage of cultures undergoing active virus production, onset and time course of cytopathic effects, and concentration of virus released into the media over time. Results showed inhibition of both herpes simplex virus-mediated cell lysis and viral replication by tobacco extracts. This is the first time that these phenomena have been demonstrated in normal human oral epithelial cells. The work described here provides evidence to support a hypothesis that herpes simplex virus type 1 and smokeless tobacco may act synergistically in oral carcinogenesis.

The transforming region of the genome of herpes simplex virus type-1 (HSV-1) encodes a peptide that raises the mutation frequency of cells. To find the effect of this peptide on cell phenotype, three types of cells were transfected with a shuttle vector plasmid that expressed the peptide. When immortalised rat fibroblasts were transfected they rapidly became anchorage-independent with high efficiency, but were not tumorigenic in nude mice. When monkey kidney cells were transfected, five clonal cell lines were isolated, of which one became anchorage-independent but was not tumorigenic in nude mice. When human oral keratinocytes were transfected they did not become immortalised. The peptide therefore induced some of the features of transformation in different cell types, but did not induce a malignant phenotype in any cell. This suggests that interaction with co-factors would be necessary for the peptide to contribute to the development of oral cancer.

Proliferative verrucous leukoplakia and hyperplasia are irreversible clinicopathologic lesions of the oral cavity and upper respiratory tract with considerable potential for evolving into verrucous or other forms of squamous cell carcinoma. Proliferative verrucous leukoplakia is a disease of the oral cavity in which verrucous hyperplasia is a part of its developmental spectrum. Verrucous hyperplasia, at other head and neck mucosal sites, may be associated with papillomas or be a de novo lesion. Human papillomavirus, as a cofactor, plays a role in some of the lesions. In the instance of verrucous hyperplasia, the authors consider it an early form of verrucous carcinoma and recommend it be treated accordingly.

Salivary duct carcinoma is a high-grade neoplasm associated primarily with the parotid gland. Its abysmal prognosis demands aggressive clinical management. Initially named after its resemblance to intraductal carcinoma of the breast, this entity derives its histogenesis from the excretory duct reserve cells, which are also the source of origin of other biologically high-grade neoplasms. As this is a lesion seldom encountered by the clinician, it is important for the pathologist to clearly make the distinction between this malignancy and more indolent neoplasms, such as terminal duct adenocarcinoma.

Polycystic kidney disease (PKD) is a life-threatening disease characterized by focal dilatations or cysts in certain kidney tubules. Changes (i.e. thickening) in the support structure for these tubules, the basement membrane, have been related to the development of the cysts. Analysis of changes in basement membranes of humans with PKD is difficult, however, due to the restricted amount of material available for study. Several genetic and induced animal models, including diphenylamine-treated rats, have been employed to study the effects of PKD on basement membrane synthesis. While all these studies agree that PKD has a significant influence on basement membranes, no clear understanding as to how PKD effects basement membrane composition has emerged. Here, we report our findings of the effect of diphenylamine treatment on the composition of the basement membrane. Our immunohistological studies indicate that bamin, a recently described glycoprotein associated with glomerular basement membranes (Robinson et al., 1989), is not present in the glomerular basement membranes of diphenylamine-treated mice. This finding was confirmed by analysis of the composition of the basement membrane matrix synthesized by EHS tumors grown in control and diphenylamine-treated mice. The possible role of bamin in the pathogenesis of renal cysts is discussed.

Epidemiologic studies show an increase in the use of smokeless tobacco but few in vitro studies have directly assessed the potential for smokeless tobacco-induced oral carcinogenesis. Oral keratinocytes were grown to 90% confluence from explants of human labial and gingival mucosa at 34 degrees C, 5% CO2 in defined media. Epithelial monolayers were subsequently subcultured and then treated for 1 hour with aqueous extracts of moist or leaf smokeless tobacco, or with 0.25 to 1.0 ng/ml of three common smokeless tobacco carcinogens: 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1-butanone; N-nitrosonornicotine; and benzo(a)pyrene. Even though the controls and most treatment groups terminally differentiated, cells exposed to 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1-butanone, N-nitrosonornicotine, and moist and dry extract continued to divide, maintained a differentiated phenotype for 8 1/2 to 10 weeks in culture, and displayed focal growth and morphologic changes suggestive of early stages in cell transformation.

Noninvasive early recognition and treatment of temporomandibular joint dysfunction remains a diagnostic challenge. This pilot study evaluated the use of phosphorus 31 magnetic resonance spectroscopy with magnetic resonance imaging to measure alterations in pH and high-energy phosphate metabolite ratios of muscle that is adjacent to an inflamed temporomandibular joint. Ten New Zealand white rabbits were used in this study. Two animals were used to develop signal acquisition protocols and to ensure that stable baseline data could be measured. In each of the eight animals used in the experiment, one temporomandibular joint was injected with a suspension of silica particles and the contralateral joint served as a control. Data were collected from control and experimental joints on days 0, 7, 14, 21, and 28, after the injection. At the end of the study, temporomandibular joints were block resected and histologically examined to confirm the presence of an inflammatory response. Results indicated that pH and metabolite ratios could be obtained by 31P-magnetic resonance spectroscopy. Changes in pH and some metabolite ratios in experimental joints showed statistical significance (p < 0.001). Differences were seen on day 2 and day 7 (p = 0.040 and p = 0.008, respectively) in the phosphocreatine/alpha-adenosine triphosphate ratios. This contrasts with phosphocreatine/beta adenosine triphosphate ratios that showed significance that began at day 7 (p = 0.022) and continued to day 14 (p = 0.025). Histologic examination indicated that the tissue response within the joint capsule was less than the granulomatous reaction expected.(ABSTRACT TRUNCATED AT 250 WORDS)

A patient was admitted to the hospital with multiple skin nodules of recent origin and signs and symptoms suggestive of acute pulmonary infection. Because one of the skin masses was located overlying the left mandibular body region, the patient was referred to the hospital dentistry clinic for evaluation. Historical, clinical, and radiographic assessments were consistent with reactive lymphadenopathy, and an intraoral excisional biopsy was performed. The biopsy results were indicative of giant cell carcinoma, which was confirmed by biopsy results from a similar skin lesion on the shoulder and by malignant cells recovered in the sputum and pleural fluids. Although this carcinoma has been shown to rarely metastasize to the skin and lymphatics of the neck, this is the first case report of metastasis to facial lymphatics.

Direct immunofluorescence employing goat anti-human IgG, IgA, IgM, C3 component of complement, fibrinogen, albumin, and polyvalent immunoglobulins was performed on postmortem samples of gingiva, parotid gland, thyroid, kidney, and pancreas tissue of 15 diabetic and 15 control patients. Basement membrane thickness quantification of kidney tubules, gingival capillaries, and parotid gland ducts and acini was also done utilizing a calibrated magnifier on uniformly enlarged photomicrographs which had been specially stained to highlight basement membranes. Results revealed binding of IgG, albumin, and polyvalent immunoglobulin to kidney glomerular and tubular basement membranes and parotid ductal and acinar basement membranes in all diabetic subjects. Thyroid follicular basement membranes were positive in 8 of 15 diabetic patients for the same antisera. All gingival and pancreatic tissue from diabetic and control patients was negative for binding of all serum proteins tested. Basement membrane thickening in kidney tubules and gingival capillaries was observed in diabetic subjects; however, there was no apparent difference between diabetic and control patients in thickness of ductal or acinar basement membranes of the parotid gland.

We report on a patient with xanthogranulomatous pyelonephritis, in situ transitional cell carcinoma, and focal prosoplasia revealing abrupt conversion of transitional epithelium to moderately well-differentiated adenocarcinoma. The etiology and pathogenesis of mucinous adenocarcinoma in the renal pelvis very likely involves the prosoplastic transition of pre-existing transitional carcinoma to adenocarcinoma. The urologist should be aware of the increased possibility of this tumor developing in a patient with longstanding infection, and frozen section should be performed more often because the gross structure of the tumor frequently appears normal. This permits the urologist to change his surgical strategy if frozen section is positive for tumor.

The purpose of the investigation was to determine the extent to which the 1984 American Heart Association prophylaxis guidelines were adopted in a sample of dental school patients and to determine whether implementation strategies resulted in change in the management of patients at risk for infective endocarditis (IE). Dental records of 330 patients requiring medical consultation on the basis of a heart problem identified in the medical history questionnaire were reviewed. One hundred fifty-four patients required IE prophylaxis according to their physicians. Only 11 percent of IE-susceptible patient charts showed documentation of correct prophylaxis for every appointment at which a bacteremia was possible. Only 35 percent of patients receiving prophylaxis after December 1984 were covered according to the new American Heart Association guidelines.

Two hundred six dental patients were tested between 1985 and 1987 for antibodies to human immunodeficiency virus (HIV) when a review of their medical histories revealed a high risk for infection. Serologic results are correlated with soft tissue and osseous findings recorded during routine head and neck and radiographic examination. Counseling recommendations for use in association with testing are outlined. A more active role for the dentist as a preventive agent is advocated to combat the spread of acquired immunodeficiency syndrome (AIDS).