Impact of the COVID-19 Pandemic on the Diagnosis of Oral and Maxillofacial Malignancies: A Retrospective Study.

OBJECTIVES: The aims of this study were to characterize the type and frequency of oral and maxillofacial malignancies in an outpatient oral pathology service and to examine the impact of COVID-19 on the diagnosis of such malignancies by dentists in Ontario, Canada. STUDY DESIGN: Our study included 775 malignancies submitted to an outpatient oral pathology service. Demographic and diagnostic data, including age, sex, submitting clinician type, anatomic site and diagnosis, were collected and analyzed for 2 periods, 2015-2019 and 2020. RESULTS: Malignancies represented 2% of total submissions to our biopsy service. Oral surface epithelial malignancies were the most common, followed by hematologic and salivary gland malignancies. During the period in which dental offices were restricted (April-May 2020), 59% fewer malignancies were submitted compared with the preceding 5 years. Despite this reduction, total malignant submissions for 2020 and post-lockdown (July-September 2020) were significantly elevated compared with previous years (p = 0.0006 and p = 0.0008, respectively). CONCLUSIONS: Our study reaffirms the important role that dentists play in the diagnosis of oral and maxillofacial malignancies. Our assessment of 2020 data highlights the impact of dental office closures on the diagnosis of oral and maxillofacial malignancies during the COVID-19 pandemic.

Mandibular Involvement Associated With Segmental Odontomaxillary Dysplasia: A Case Series.

Segmental odontomaxillary dysplasia (SOD) is an uncommon and likely underrecognized developmental condition. In rare cases, SOD can also result in anomalies of the ipsilateral mandibular alveolar process and teeth. This report presents two cases of SOD with mandibular involvement to highlight this potential variation in SOD presentation. These cases help shed new light on our understanding of the disease mechanism and pathoetiology, while also informing clinicians to be diligent in imaging the ipsilateral mandible for dental anomalies in their patients with SOD. Based on the involvement of both jaws, the name change to 'segmental ipsilateral odontognathic dysplasia' is justified to better reflect its pathophysiology.

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.

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.

Oral Squamous Cell Carcinoma Associated with Precursor Lesions.

Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P < 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor (P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE: OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer.

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.

Surrogate markers for high-risk human papillomavirus infection in oral epithelial dysplasia: A comparison of p16, Ki-67, and ProExC.

OBJECTIVE: The aim of this study was to determine the utility of surrogate markers of human papillomavirus (HPV) infection in the diagnosis of HPV-associated oral epithelial dysplasia (OED). STUDY DESIGN: Twelve cases of oral dysplasia with histologic features of HPV infection were stained with surrogate markers for HPV (p16, Ki-67, and ProExC) on immunohistochemistry. A second group of 12 cases of oral dysplasia without histologic features of HPV infection was used for comparison. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the presence of high-risk HPV (HR HPV) in p16-positive cases. RESULTS: All of the surrogate markers showed a statistically significant association with HPV-positive OED (P < .001). The agreement between p16 and HPV positivity was the strongest (κ = 1.00), whereas Ki-67 showed very good association with HPV (κ = 0.83), and ProExC showed good association (κ = 0.75). In each case, the agreement was statistically significant (P < .001). Overall, each of the 3 markers showed good sensitivity; however, ProExC showed the lowest specificity. CONCLUSIONS: The clinicopathologic features of 12 cases of HPV OED are reported. Diffuse p16 positivity is an accurate and reliable method for predicting HR HPV infection in both high and low grade cases of epithelial dysplasia with histopathologic features of HPV OED. The use of Ki-67 and ProExC did not demonstrate any additional diagnostic benefit in the diagnosis HPV OED.

Association of human papilloma virus with atypical and malignant oral papillary lesions.

OBJECTIVE: This study aimed to examine atypical and malignant papillary oral lesions for low- and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. STUDY DESIGN: Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison. RESULTS: Low-risk HPV was found in 10 of 66 cases, including 9 APLs and 1 papilloma. All low-risk HPV-positive cases showed suprabasilar MIB-1 staining, and the agreement was statistically significant (P < .0001). Diffuse p16 staining combined with high-risk HPV was not seen in any of the cases. A subset of HPV(-) APLs progressed to carcinoma. CONCLUSIONS: Oral papillary lesions are a heterogeneous group. Low-risk HPV infection is associated with a subset of APLs with a benign clinical course. Potentially malignant APLs and MPLs are not associated with low- or high-risk HPV.

Association of high-risk human papillomavirus infection with oral epithelial dysplasia.

OBJECTIVE: The aim of this study was to evaluate cases of oral epithelial dysplasia for biologically significant human papillomavirus (HPV) infection. STUDY DESIGN: Forty consecutive cases of high-grade dysplasia and 37 cases of low-grade dysplasia were examined for p16(INK4a) expression by immunohistochemistry. High-risk HPV infection was assessed in p16-positive cases using in situ hybridization. Proliferation index was assessed with MIB-1 immunohistochemistry. RESULTS: Eleven of 40 high-grade dysplasias and one of 37 low-grade dysplasias were p16 positive. High-risk HPV was detected in seven cases of p16-positive high-grade dysplasia. The difference between high- and low-grade dysplasia was statistically significant (P = .01). HPV-positive high-grade dysplasias showed a distinctive histologic appearance and MIB-1 labeling pattern. Most high-risk HPV-positive cases were seen in the floor of mouth. CONCLUSION: High-risk HPV was associated with a subset of cases of severe epithelial dysplasia/carcinoma in situ that demonstrated diffuse loss of squamous differentiation and a high proliferation index.

Markers of potential malignancy in chronic hyperplastic candidiasis.

AIM: To examine the presence of markers associated with malignancy, including p53, p21 cyclin-dependent kinase inhibitor 1A, murine double minutes-2, and others, in chronic hyperplastic candidiasis. METHODS: Immunohistochemical methods were used to examine the expression of p53, murine double minutes-2, p21 cyclin-dependent kinase inhibitor 1A, metallothionein, and proliferating cell nuclear antigen in 42 chronic hyperplastic candidiasis lesions and 11 non-infected control tissues. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling was used to examine apoptosis, which was correlated with p53 expression. These markers were measured in lesions of chronic hyperplastic candidiasis that did not show any epithelial dysplasia or histological signs of malignancy. RESULTS: p53 scores were higher in chronic hyperplastic candidiasis than in controls (P = 0.0046). Murine double-minutes 2 levels were not elevated. p21 cyclin-dependent kinase inhibitor 1A was increased in parabasal (P < 0.0001) and basal epithelial cells. Chronic hyperplastic candidiasis lesions showed a similar basal/parabasal metallothionein staining pattern to that seen in normal squamous epithelium. Proliferating cell nuclear antigen was increased (P = 0.0007), as was apoptosis (P = 0.0033). CONCLUSION: Increased p53 in oral chronic hyperplastic candidiasis suggests an increased potential for malignant change in the epithelium, above that of normal tissues. Further functional investigation is required, as well as clinical follow-up studies.