Cysts of the jaws: A multicentre study.

OBJECTIVES: To determine the relative frequency, demographic and pathologic profiles of patients diagnosed with cysts of the jaws. MATERIALS AND METHODS: Biopsy records of the participating institutions from 2000 to 2020 were reviewed for lesions diagnosed in the cyst category. Demographic data, the location of the cysts and pathologic diagnoses were collected. Data were analyzed by appropriate statistics using IBM SPSS software version 28.0. RESULTS: From 148,353 accessioned cases, 25,628 cases (17.28%) were diagnosed in the cyst category. Mean age of the patients ± SD = 42.62 ± 19.36 years. Paediatric patients (aged ≤ 16 years) accounted for 9.63%, while geriatric patients (aged ≥ 65) comprised 14.22% of all the patients. The male-to-female ratio was 1.27:1. The majority of the lesions were encountered in the mandible. The most prevalent cyst was radicular cyst followed by dentigerous cyst and odontogenic keratocyst. In the paediatric group, dentigerous cyst was the most prevalent, whereas in the geriatric group, radicular cyst was the most common. CONCLUSIONS: In general, the results of this study are in accordance with previous studies. This study provides an invaluable database for clinicians when formulating clinical differential diagnoses as well as for pathologists in rendering the final diagnosis.

Oral Hairy Leukoplakia in Patients With No Evidence of Immunosuppression: A Case Series and Review of the Literature.

OBJECTIVES: Oral hairy leukoplakia (OHL) is caused by Epstein-Barr virus (EBV) and is often associated with HIV and other immunosuppressive conditions. It is rare in HIV-negative patients, but has been reported in patients who use immune-modulating medications (e.g., cyclosporine). The objectives of this study were to determine the occurrence of OHL in HIV-negative patients and report Langerhans cell counts in these lesions. STUDY DESIGN: A series of 7 new cases of OHL among HIV-negative patients is described. Langerhans cells were counted using an immunoperoxidase stain for CD1a and light microscopy. RESULTS: The 7 patients were male, ranging in age from 26 to 69 years. Clinically, all lesions were diagnosed as leukoplakia on the lateral border of the tongue. Microscopic examination revealed hyperparakeratosis and candidiasis in some cases, acanthosis and a band-like zone with clearing of cells in the upper spinous layer, which were EBV-positive by in-situ hybridization. There was a significant decrease in Langerhans cell counts in OHL patients. CONCLUSION: OHL can occur in HIV-negative patients.

TMJ Changes in Adolescent TMD Patients Seen on MRI in Clinical Setting.

UNLABELLED: To determine whether temporomandibular joint (TMJ) changes are similar between adolescent and older TMJ disorder (TMD) patients, a retrospective chart review for TMJ MRIs was done for disc and bone changes. Patients were divided into adolescent, adult and elderly groups. RESULTS: The groups had similar prevalence of joint changes and number of joints involved. Disc changes were more prevalent in adolescents (p = 0.008), while bone changes were more prevalent in the elderly group (p = 0.10). Anterior disc displacement was the most common finding and was most prevalent in adolescents (p < 0.001). CONCLUSION: Adolescents display similar disc/bone changes in their TMJ as older TMD patients.

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice.

The P2X7 receptor is an ATP-gated cation channel expressed by a number of cell types. We have shown previously that disruption of P2X7 receptor function results in downregulation of osteogenic markers and upregulation of adipogenic markers in calvarial cell cultures. In the present study, we assessed whether loss of P2X7 receptor function results in changes to adipocyte distribution and lipid accumulation in vivo. Male P2X7 loss-of-function (KO) mice exhibited significantly greater body weight and epididymal fat pad mass than wild-type (WT) mice at 9 months of age. Fat pad adipocytes did not differ in size, consistent with adipocyte hyperplasia rather than hypertrophy. Histological examination revealed ectopic lipid accumulation in the form of adipocytes and/or lipid droplets in several non-adipose tissues of older male KO mice (9-12 months of age). Ectopic lipid was observed in kidney, extraorbital lacrimal gland and pancreas, but not in liver, heart or skeletal muscle. Specifically, lacrimal gland and pancreas from 12-month-old male KO mice had greater numbers of adipocytes in perivascular, periductal and acinar regions. As well, lipid droplets accumulated in the renal tubular epithelium and lacrimal acinar cells. Blood plasma analyses revealed diminished total cholesterol levels in 9- and 12-month-old male KO mice compared with WT controls. Interestingly, no differences were observed in female mice. Moreover, there were no significant differences in food consumption between male KO and WT mice. Taken together, these data establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism in an age- and sex-dependent manner.

Progression to malignancy in oral potentially malignant disorders: a retrospective study of 5,036 patients in Ontario, Canada.

OBJECTIVES: Determine the rate of malignant transformation (MT) of oral potentially malignant disorders (OPMDs) and risk factors for transformation. STUDY DESIGN: The OPMD database (2001-2015) from 2 biopsy services in Ontario, Canada, was linked to the Ontario Cancer Registry to determine the rate of progression to oral squamous cell carcinoma (OSCC). Clinical and histologic features of progressed and non-progressed cases were compared to determine risk factors for progression. RESULTS: The MT rate was 6.4% (322/5,036 cases). The mean time for cancer development was 51.2 months. 33.6% of cases (107/322) progressed after over 60 months. The risk of cancer increased with age and was higher in non-smokers. The MT rate was highest in the tongue (11.4%), followed by the floor of mouth (7.1%) and gingiva (6.5%). Histologic grade was associated with progression to cancer (P < .0001). Atypical verrucous-papillary lesions with no or mild dysplasia predominantly affected older patients' gingiva, and the progression rate was significantly higher than conventional mild dysplasia (9.2% vs 3.2%, P = .0002). CONCLUSIONS: Our population-based retrospective study showed that <10% of OPMDs progressed to cancer, which could take many years. Atypical papillary-verrucous proliferation without high-grade dysplasia is a subtype of OPMD requiring further study.

Immunohistochemical Characterization of Gingival Fibromas.

PURPOSE: Gingival fibromas (GFs) are fibrous lesions of the gingiva that are not well defined in the literature. They are histologically similar to peripheral ossifying fibromas (POFs), both being characterized as cellular proliferations of dense fibrous tissue, with POFs differing in that they demonstrate foci of calcification. This study aims to expand upon the immunohistochemical characterization of GFs, and to confirm their osteoblastic phenotype. METHODS: Formalin fixed, paraffin embedded GFs, POFs and fibroepithelial polyps (FEPs) of the gingiva were examined. Immunohistochemical staining was performed for special AT-rich sequence binding protein 2 (SATB2), runt-related transcription factor 2 (RUNX2), osteocalcin and alpha-smooth muscle actin (αSMA). Sections were evaluated by light microscopy and the immunohistochemical staining patterns were assigned immunoreactive scores (IRS) based on percentage of stained cells and intensity of staining. RESULTS: GFs, POFs, and FEPs of the gingiva expressed osteoblastic markers SATB2, RUNX2 and osteocalcin. GFs and POFs expressed αSMA while FEPs of the gingiva did not. GFs and POFs had similar staining patterns of SATB2, RUNX2 and αSMA. DISCUSSION: These findings demonstrate that GFs and POFs exhibit a similar immunohistochemical profile, and supports a theory that GFs are osteoblastic lesions possibly related to POFs.

Assessing Oral Epithelial Dysplasia Risk for Transformation to Cancer: Comparison Between Histologic Grading Systems Versus S100A7 Immunohistochemical Signature-based Grading.

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen's kappa ( K ) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement ( Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P =0.231; ( P >>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement ( Kw =0.892) and was a good indicator of transformation to cancer ( P =0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.

Sole dermatitis in children: patch testing revisited.

Although dermatoses affecting the soles of the feet in children are regularly encountered in dermatology clinics, the relationship with allergic contact dermatitis affecting this part of the foot is not well established. The aim of this study was to evaluate the relevance of patch testing children with sole dermatoses. We reviewed the results of all patch tests performed in children (<18 years) presenting with dermatoses involving the soles between 1997 and 2009 from our departmental patch test database. Forty-one children were identified: 27 children with an inflammatory dermatitis affecting the sole and 14 children with juvenile plantar dermatosis (JPD). Seventeen (41%) children had at least one clinically relevant positive patch test reaction. Rubber additives and potassium dichromate were the most frequent allergens identified. Forty-eight percent of children with inflammatory dermatitis affecting the sole and 29% of children with JPD had at least one relevant reaction. Of the children with relevant reactions, 76% had a personal or family history of atopy. Our results demonstrate the importance of patch testing children with dermatoses affecting the soles and indicate that a history of atopy or a diagnosis of JPD should not deter investigation.

Investigation of the Molecular Profile of Granular Cell Tumours and Schwannomas of the Oral Cavity.

Granular cell tumours (GCTs) are rare submucosal lesions, thought to develop from Schwann cells, characterised by large polygonal cells with abundant lysosomes. The objectives of this study are to investigate whether GCTs have an antigen-presenting cell (APC) phenotype or a neural crest phenotype using immunohistochemistry and to compare expression profiles with Schwannomas. Immunoreactivity to CD68, HLA-DR, CD163, CD40 and CD11c (APC phenotype) and markers of neural crest cell (NCC) origin S100, SOX10, NSE and GAP43 in 23 cases of GCTs and 10 cases of Schwannomas were evaluated. RT-qPCR was used to identify a possible NCC developmental phenotype in 6 cases of GCTs. GAP43 was identified as a new NCC marker for GCTs, and some evidence was found for an APC phenotype from CD68 and HLA-DR immunoreactivity. RT-qPCR failed to identify an NCC developmental phenotype of GCTs, likely due to technical issues.

Metastases to the mouth and jaws: a contemporary Canadian experience.

BACKGROUND AND OBJECTIVE: The types of cancers that most frequently metastasize to the mouth and jaws reflect, for the most part, the relative incidence of cancers in a given population at a given time. We report a retrospective, but relatively contemporary study of 38 cases of metastatic oral tumours in a Canadian population to compare the Canadian experience with that of nearby and distant countries. METHODS: Thirty-eight cases of metastatic disease to the mouth and jaws in a Canadian population were analyzed. Data about patients' age, sex, site of metastatic deposits, clinical history, including the presence of a known primary cancer, and radiographic features were collected from the files (1992-2010) of the oral pathology diagnostic service at the University of Western Ontario, and the hospital archives (2002-2010) of the department of pathology, London Health Sciences Centre, London, Ontario. RESULTS: Most metastases were to the mandible, although oral soft tissues were also involved, most frequently, the gingiva and mucosa of the alveolar ridge. Prostate, lung and breast cancers were the most common primary sites, but a variety of cancer types were found. CONCLUSIONS: The relative frequency of types of metastatic cancer to the oral region is similar in Canada, the United States and Northern Europe, but differs significantly from those reported in South East Asia and Japan. The relative frequency of types of cancer that metastasize to the mouth and jaws reflects the relative incidence of cancers in the population.

Human Tissue Kallikreins in Polymorphous Adenocarcinoma: A Polymerase Chain Reaction and Immunohistochemical Study.

Polymorphous adenocarcinoma (PAC) is the second most common malignant salivary gland tumour of minor salivary glands. Human tissue kallikreins (KLKs) are a family of highly conserved serine proteases expressed by various tissues and organs. The literature demonstrates a link between KLKs and salivary gland neoplasms. The purpose of this study was to determine levels of KLK mRNA in tissue samples of PAC and to determine if KLK expression is limited to tumour cells. Nineteen cases of PAC were reviewed (1987-2013). The diagnosis was confirmed, demographic data was collected, and formalin fixed paraffin-embedded PAC and normal salivary gland tissue samples were obtained. RNA isolation was achieved, followed by conversion to complementary DNA via reverse transcription. Using PCR, the quantitative level of expression of KLKs1-15 was recorded. Samples exhibiting high and low KLK expression were selected for immunohistochemistry staining. Results revealed a statistically significant increase in mean KLK mRNA expression for KLK1, KLK4, KLK10, KLK12 and KLK15 in PAC tissue samples, compared with normal salivary gland tissue (Mann-Whitney U test, p < 0.05). Immunohistochemistry results demonstrated that KLKs were present in tumor cells. Notably, all samples demonstrating relatively higher KLK mRNA expression showed equivalent or increased staining scores relative to the low KLK mRNA expression samples. In conclusion, there appears to be aberrant kallikrein expression in polymorphous adenocarcinoma, suggesting the possibility of a kallikrein cascade influence on tumor development and progression.

Oral Potentially Malignant Disorders (OPMD): What is the clinical utility of dysplasia grade?

INTRODUCTION: Oral epithelial dysplasia is considered a potential histologic precursor of subsequent squamous cell cancer. As standard clinical practice, pathologists grade dysplasia to assess risk for progression to malignancy. Except for the most advanced grade, severe dysplasia, dysplasia grading has failed to correlate well with the risk to develop invasive cancer. The questions of what process dysplasia grading best represents and what clinical utility dysplasia grading may have are explored. AREAS COVERED: This narrative review is based on PubMed search with emphasis on papers since 2010. Epithelial dysplasia as a precursor lesion of cancer and dysplasia grading as a risk assessment tool for progression to cancer are discussed. The close clinical association of dysplasia with known carcinogens, alcohol, and tobacco products is presented. EXPERT OPINION: Oral epithelial dysplasia is often, associated with prolonged exposure to tobacco and alcohol products. With reduction of carcinogen exposure, dysplasia is known to regress in some cases. It is proposed that histologic dysplasia grade together with macroscopic images of dysplastic clinical lesions be used as an educational tool to incentivize patients to reduce their known carcinogen exposure. This strategy has the potential to reduce lesion progression thereby reducing the disease burden of oral cancer.

Human kallikrein 14 (KLK14) expression in salivary gland tumors.

OBJECTIVE: To analyze the expression of human kallikrein 14 (KLK14) in salivary gland tumors. METHODS: A standard immunoperoxidase staining technique was used to assess the expression profile of KLK14 in normal salivary glands and tumors including pleomorphic adenoma (PA; n=17), adenoid cystic carcinoma (ACC; n=13) and mucoepidermoid carcinoma (MEC; n=9). Tumor stage, grade, patient age and gender, and site of occurrence were recorded. These clinical parameters were correlated with KLK14 levels in malignant tumors. The expression profiles for KLK3, 5, 6, 8 and 13 were also retrieved. RESULTS: Normal salivary glands, PA, ACC and MEC showed strong expression of KLK14 in ductal and non-ductal cells. Both PA and ACC showed higher KLK14 levels than normal glands and MEC tissues. There were no statistically significant associations between levels of KLK14 and clinical parameters. CONCLUSIONS: The differences in the levels of KLK14 suggest that KLKs may aid in the differential diagnosis of salivary gland tumors. The coexpression of KLKs suggests their possible involvement in an enzymatic pathway activated in salivary gland. KLK14 may be a promising new biomarker in salivary gland tumors.

Kallikrein-Related Peptidase mRNA Expression in Adenoid Cystic Carcinoma of Salivary Glands: A Polymerase Chain Reaction Study.

Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases implicated in a variety of biological processes. Aberrant expression of KLKs has been associated with the development of certain cancers. However, the role of KLKs in salivary tumors has not been extensively studied. This study evaluated the expression of KLKs in both adenoid cystic carcinoma (ACC) and normal salivary gland tissue. We isolated total RNA from 39 formalin-fixed, paraffin-embedded samples, which included 24 ACCs and 15 normal salivary gland tissues. Complementary DNA, synthesized by reverse transcription, was combined with gene specific kallikrein primers (KLK1-KLK15) to allow for quantitative real-time PCR. Data was normalized to a ß-actin housekeeping gene. Relative quantification analysis was performed using the ΔCq method. KLK1-KLK15 expression was observed in both tissue types. However, KLK1, KLK8, KLK11, and KLK14 were found to be downregulated in ACC. We propose that this may represent a multi-parametric panel providing diagnostic and prognostic information.

Taste and Pain Response in Burning Mouth Syndrome With and Without Geographic Tongue.

AIMS: To assess the effect of geographic tongue (GT) on taste, salivary flow, and pain characteristics in burning mouth syndrome (BMS) to determine whether GT is a contributing factor to BMS and whether BMS and GT represent similar patient populations. METHODS: A retrospective chart study was conducted. Patients with a diagnosis of BMS or BMS/GT were included. Data regarding smell testing, spatial taste-testing, salivary flow, oral pH, and subjective pain rating on a generalized labeled magnitude scale (gLMS) were collected. RESULTS: No significant differences in age, gender, oral pH, smell, or pain were found between groups. Stimulated and unstimulated salivary flow were significantly lower in BMS/GT. Taste responses to all taste stimuli and to ethanol were significantly lower in BMS, with the exception of sour at the fungiform papillae. CONCLUSION: BMS and BMS/GT present with similar clinical pain phenotype and demographics; however, taste was more intact in BMS/GT, suggesting that GT may be a contributing factor in the development of BMS through a mechanism that does not involve taste.

Pain reduction in burning mouth syndrome (BMS) may be associated with selective improvement of taste: a retrospective study.

OBJECTIVE: The aim of this study was to examine taste function in patients who reported improvement in their pain level after treatment to determine if pain reduction is associated with change in taste function in patients with burning mouth syndrome (BMS). STUDY DESIGN: This retrospective study of patients with BMS was conducted at a private oral medicine clinic. RESULTS: Thirty-nine patients with BMS (31 females and 8 males; mean age 56.1 ± 9.4 years) reported improvement in their pain in 1 to 22 months after the initial visit (mean 5.13 ± 4.18). The most commonly used medication was clonazepam 0.25 to 0.5 mg/day. Twenty-eight patients were treated with a combination of medications. "Salt" and "bitter" responses at the fungiform papillae were increased after treatment (P = .026 and P = .044, respectively). "Salt" responses at the circumvallate papillae also increased (P < .001). Pain reduction was significant after treatment in the morning (P = .002) and in the evening (P < .001). CONCLUSIONS: Treatment of BMS can significantly decrease pain symptoms, resulting in improvement in taste function. Pain reduction often requires a combination of medications.

Histologic and Immunopathologic Variability in Primary Intraoral Angiosarcoma: A Case Report and Review of the Literature.

Primary intraoral angiosarcoma is an exceptionally rare malignancy of vascular origin which can be challenging to diagnose due to microscopic and immunohistochemical variability. A histopathologically challenging case of primary intraoral angiosarcoma, occurring in a pediatric patient is presented. A comprehensive review of the literature reveals that primary intraoral angiosarcomas occur with nearly equal frequency in males and females, affect the gingiva and the tongue most commonly and are treated primarily with surgery. As with angiosarcoma in other sites, primary intraoral angiosarcoma behaves aggressively with the majority of patients succumbing to their disease.

Ligneous gingivitis secondary to plasminogen deficiency: a multidisciplinary diagnostic challenge.

Plasminogen deficiency is a genetic condition resulting in deposition of extravascular fibrin within mucosal tissues. Lesions associated with plasminogen deficiency most commonly affect the eyes, while intraoral lesions, when present, affect the marginal aspects of the gingiva. We report a diagnostically challenging case of ligneous gingivitis, which developed in a young male patient in the absence of other clinical lesions. Due to the rarity of this condition, it may fall under the radar of dentists and dental specialists, leading to missed or delayed diagnosis.