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.

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.

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.

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.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Gingival cyst of the adult.

The gingival cyst of the adult (GCA) is a rare odontogenic cyst, consisting of 0.3% of all odontogenic cysts. This case report, based on CARE guidelines for case reports, aims to present a case of a 52-year-old female patient with a symptomatic translucent nodule in the upper left anterior gingiva, measuring approximately 6mm. Excisional biopsy was performed, and the histological examination revealed multiple cystic cavities lined by the squamous epithelium of varying thickness with focal areas of nodular thickenings. The presence of clusters of cells with clear cytoplasm within epithelial thickenings was observed. PAS staining was negative in clear cells. The diagnosis of the GCA was established. Despite its rarity, GCA should be considered in the differential diagnosis of gingival lesions. Conservative surgical treatment proved to be effective, with no signs of recurrence.

Sociodemographic and clinical characterization of cases of 1,103 non-syndromic and 66 syndromic odontogenic keratocyst: a Brazilian multicenter study.

OBJECTIVES: This multicenter study aimed to evaluate cases of non-syndrome and syndromic odontogenic keratocyst, as well as cases of recurrence within these two groups. METHODS: This descriptive, analytical, retrospective cross-sectional study evaluated the sex, age and presence of multiple lesions in 1,169 individuals seen at 10 Brazilian oral and maxillofacial pathology centers. Of these, 1,341 odontogenic keratocysts were analyzed regarding clinical diagnosis, size, site, imaging appearance, signs and symptoms, type of biopsy, treatment, and recurrence. RESULTS: There was a similar distribution by sex. The median age of non-syndromic and syndromic patients was 32 and 17.5 years, respectively. The posterior mandible was the site most affected by small and large lesions in both groups and in recurrent cases. Unilocular lesions were more frequent, also in recurrent cases. Mainly small lesions showed this imaging appearance. Signs and symptoms were absent in most cases. Conservative treatment was the most frequent modality in all age groups, regardless of the patient's condition and recurrence. Recurrences were uncommon. CONCLUSION: This study showed a higher frequency of non-syndromic keratocysts in the population. Clinicopathological features related to the involvement of multiple sites, age, and recurrence may differ between syndromic and non-syndromic cases. Furthermore, we found an association between lesion size and some clinical features and between the time interval to recurrence and the syndromic spectrum. CLINICAL RELEVANCE: To contribute to a better understanding of the distribution and association between clinical, imaging, and sociodemographic characteristics in each spectrum of the lesion.

A primary oral mucosal melanoma of the hard palate with no recurrence: Report of a 10 years follow-up.

BACKGROUND: Primary oral mucosal melanoma (OMM) represents an extremely rare and aggressive tumor that arises from malignant transformation and clonal expansion of melanocytes in the oral cavity. The prognosis of patients affected by OMM is quite unfavorable, with survival rates lower than those described for patients with cutaneous melanoma. CASE REPORT: Here, we report a case of OMM in a 59-year-old Caucasian woman, who was referred for evaluation of a large asymptomatic pigmented lesion on the left side of the hard palate under the removable total denture. Incisional biopsy was performed, and histopathological analysis revealed the proliferation of spindle-shaped and pigmented epithelioid cells, with cellular pleomorphism. These cells were positive for Melan A, S-100, HMB-45, SOX-10, and Ki-67 confirming the diagnosis of OMM. The patient underwent partial maxillectomy and adjuvant radiotherapy. After treatment, she was rehabilitated with a palatal obturator prosthesis and has been in follow-up for 10 years with no evidence of disease. Due to the rarity in the oral cavity and the nonspecific signs and symptoms, the diagnosis of OMM is difficult and often overlooked. CONCLUSION: Therefore, multidisciplinary management from diagnosis, treatment, and rehabilitation is important to increase the expectation of cure.

Clinicopathological Features of Metastasis to the Oral and Maxillofacial Region-Multicenter Study.

BACKGROUND: This study aimed to investigate the clinicopathological features of metastases in the oral and maxillofacial regions. METHODS: In this retrospective study, biopsy records were obtained from referral centers for oral and maxillofacial diagnosis in Brazil, Guatemala, Mexico, and South Africa. RESULTS: A total of 120 cases were evaluated. Of these, 53.78% affected female patients, with a mean age of 57.64 years. Intraosseous lesions were more frequent, particularly in the posterior region of the mandible (49.58%). Clinically, most cases presented with symptomatic swelling, with an average evolution time of 25 months. The clinical diagnostic hypothesis in most instances was that of a malignant lesion. Breast cancer was the most common primary tumor location in females, while lung origin was most common in males. In most cases, the primary cancer was an adenocarcinoma (44.73%). The follow-up period was available for 29 cases, and out of these, 20 had died due to the disease. CONCLUSION: Although this is a rare condition, clinicians should be aware that any oral lesions have the possibility of being metastatic, particularly in individuals with a previous history of cancer. The findings from this study could assist clinicians in prompt diagnosing these lesions and subsequent conducting oncologic assessments and treatment.

Human Papillomavirus-Associated Oral Epithelial Dysplasia: Report of 5 Illustrative Cases from Latin America.

BACKGROUND: Human papillomavirus-associated oral epithelial dysplasia (HPV-OED) is a distinct oral epithelial disorder characterized by viral cytopathic changes caused by transcriptionally active high-risk HPV. The aim of the present study was to report 5 additional cases from Latin America. METHODS: Clinical data from five patients with HPV-OED were obtained from the archives of three oral pathology services from Brazil and Chile. All cases were submitted to morphological, p16 expression and in situ hybridization (ISH) for HPV analyses. RESULTS: Four patients were male and one patient was female, with a mean age of 55.4 years. Four patients were HIV seropositive and two were smokers. Three cases affected the buccal mucosa and commissure, one of which had an additional plaque in the soft palate, and one case each occurred on the floor of mouth and lower labial mucosa. Most cases presented as well-demarcated white plaques with a verrucous surface. One case presented multiple lesions ranging from normal to white-colored slightly elevated plaques with a cobblestone surface. Peripheral mucosal pigmentation was observed in two cases. All five cases presented with the characteristic microscopic features of HPV-OED, including severe dysplasia with numerous karyorrhectic and apoptotic cells, full-thickness "block positivity" for p16 and high Ki-67 index (> 90%) sharply demarcated from the adjacent non-dysplastic epithelium. Wide-spectrum DNA ISH-HPV was positive in 4 cases. All patients were treated with conservative surgical excision with no signs of recurrence after a mean of 39-month follow-up. CONCLUSION: This represents the first series of HPV-OED from Latin America; most cases presented as well-demarcated papillary white plaques affecting the buccal mucosa and commissure of HIV-positive middle-aged men, two of them exhibiting peripheral pigmentation caused by reactive melanocytes. The typical microscopic findings of HPV-OED were observed in all cases, which also showed strong p16 positivity in a continuous band through the full thickness of the epithelium and high Ki67.

Oral squamous cell carcinomas and oral potentially malignant disorders: A Latin American study.

OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.

Development and validation of a multivariable model for prediction of malignant transformation and recurrence of oral epithelial dysplasia.

BACKGROUND: Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes. METHODS: A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases. Multivariable models were developed to evaluate prediction of OED recurrence and malignant transformation. The best performing models were externally validated on unseen cases pooled from four different centres (n = 121), of which 32% progressed to cancer, with an average transformation time of 45 months. RESULTS: Grade-based differences were seen for cytoplasmic eosin, nuclear eccentricity, and circularity in basal epithelial cells of OED (p < 0.05). Nucleus circularity was associated with OED recurrence (p = 0.018) and epithelial perimeter associated with malignant transformation (p = 0.03). The developed model demonstrated superior predictive potential for malignant transformation (AUROC 0.77) and OED recurrence (AUROC 0.74) as compared with conventional WHO grading (AUROC 0.68 and 0.71, respectively). External validation supported the prognostic strength of this model. CONCLUSIONS: This study supports a novel prognostic model which outperforms existing grading systems. Further studies are warranted to evaluate its significance for OED prognostication.

Deep learning applied to the histopathological diagnosis of ameloblastomas and ameloblastic carcinomas.

BACKGROUND: Odontogenic tumors (OT) are composed of heterogeneous lesions, which can be benign or malignant, with different behavior and histology. Within this classification, ameloblastoma and ameloblastic carcinoma (AC) represent a diagnostic challenge in daily histopathological practice due to their similar characteristics and the limitations that incisional biopsies represent. From these premises, we wanted to test the usefulness of models based on artificial intelligence (AI) in the field of oral and maxillofacial pathology for differential diagnosis. The main advantages of integrating Machine Learning (ML) with microscopic and radiographic imaging is the ability to significantly reduce intra-and inter observer variability and improve diagnostic objectivity and reproducibility. METHODS: Thirty Digitized slides were collected from different diagnostic centers of oral pathology in Brazil. After performing manual annotation in the region of interest, the images were segmented and fragmented into small patches. In the supervised learning methodology for image classification, three models (ResNet50, DenseNet, and VGG16) were focus of investigation to provide the probability of an image being classified as class0 (i.e., ameloblastoma) or class1 (i.e., Ameloblastic carcinoma). RESULTS: The training and validation metrics did not show convergence, characterizing overfitting. However, the test results were satisfactory, with an average for ResNet50 of 0.75, 0.71, 0.84, 0.65, and 0.77 for accuracy, precision, sensitivity, specificity, and F1-score, respectively. CONCLUSIONS: The models demonstrated a strong potential of learning, but lack of generalization ability. The models learn fast, reaching a training accuracy of 98%. The evaluation process showed instability in validation; however, acceptable performance in the testing process, which may be due to the small data set. This first investigation opens an opportunity for expanding collaboration to incorporate more complementary data; as well as, developing and evaluating new alternative models.