Intraosseous benign peripheral nerve sheath tumor of the jaws: report of 4 new cases and a comprehensive literature review.

Benign peripheral nerve sheath tumors (BPNSTs) are a vast, common, heterogeneous group of lesions that are often diagnostically challenging. The head and neck region is recognized as the second most common location for these lesions, especially the tongue. However, BPNSTs occurring centrally within the jaw bones are exceedingly rare. To date, approximately 161 cases of intraosseous BPNSTs have been reported in the jaws. This group mainly includes the relatively more common neurofibromas and schwannomas, and the less common perineuriomas and hybrid forms. Unlike soft tissues, schwannomas are the most common BPNSTs occurring within the jaws, followed by neurofibromas and perineuriomas. These neoplasms can present as a well-defined unilocular lesion or as an ill-defined multilocular image, resembling several types of benign and malignant lesions of odontogenic origin. The aim of the current study was to report 4 new cases of intraosseous BPNSTs and a comprehensive literature review.

Oral/Perioral Reactions to Injectable Soft Tissue Fillers: A Clinicopathological Multicentric Study.

OBJECTIVE: To analyze the characteristics of a series of oral reactions to injectable soft tissue fillers. MATERIALS AND METHODS: Cases diagnosed as oral reactions to injectable soft tissue fillers were selected from eight Pathology laboratories. Information was retrieved from the laboratory charts and from the review of the hematoxylin and eosin-stained histological slides. RESULTS: The 151 patients showed a mean age of 54.9 years, and 136 (90.1%) were females. Mean time of onset was 20.4 months, and the lips were the most frequent location (72.8%). Most cases presented as asymptomatic isolated nodules, with a mean size of 17.4 mm. Silicone (38.5%), polymethylmetacrylate (33%), and hyaluronic acid (11.9%) were the three most common fillers. Granulomas, foamy macrophages, and multinucleated giant cells were observed in 44%, 51.5%, and 65.3% of the cases, respectively. Time of onset was shorter for males (p = 0.033), and symptoms were common in the upper lip, buccal mucosa, and lower vestibule (p = 0.010). Foamy macrophages were more common in association with silicone and collagen (p < 0.001), whereas multinucleated giant cells were more common in association with polymethylmetacrylate, hydroxiapatite, and polylactic acid (p = 0.012). CONCLUSION: Clinicians should consider reactions to injectable soft tissue fillers when evaluating asymptomatic submucosal nodules affecting the lips of adult/older females.

Development and Evaluation of a Convolutional Neural Network for Microscopic Diagnosis Between Pleomorphic Adenoma and Carcinoma Ex-Pleomorphic Adenoma.

AIMS: To develop a model capable of distinguishing carcinoma ex-pleomorphic adenoma from pleomorphic adenoma using a convolutional neural network architecture. METHODS AND RESULTS: A cohort of 83 Brazilian patients, divided into carcinoma ex-pleomorphic adenoma (n = 42) and pleomorphic adenoma (n = 41), was used for training a convolutional neural network. The whole-slide images were annotated and fragmented into 743 869 (carcinoma ex-pleomorphic adenomas) and 211 714 (pleomorphic adenomas) patches, measuring 224 × 224 pixels. Training (80%), validation (10%), and test (10%) subsets were established. The Residual Neural Network (ResNet)-50 was chosen for its recognition and classification capabilities. The training and validation graphs, and parameters derived from the confusion matrix, were evaluated. The loss curve recorded 0.63, and the accuracy reached 0.93. Evaluated parameters included specificity (0.88), sensitivity (0.94), precision (0.96), F1 score (0.95), and area under the curve (0.97). CONCLUSIONS: The study underscores the potential of ResNet-50 in the microscopic diagnosis of carcinoma ex-pleomorphic adenoma. The developed model demonstrated strong learning potential, but exhibited partial limitations in generalization, as indicated by the validation curve. In summary, the study established a promising baseline despite limitations in model generalization. This indicates the need to refine methodologies, investigate new models, incorporate larger datasets, and encourage inter-institutional collaboration for comprehensive studies in salivary gland tumors.

Deep Convolutional Neural Network for Accurate Classification of Myofibroblastic Lesions on Patch-Based Images.

OBJECTIVE: This study aimed to implement and evaluate a Deep Convolutional Neural Network for classifying myofibroblastic lesions into benign and malignant categories based on patch-based images. METHODS: A Residual Neural Network (ResNet50) model, pre-trained with weights from ImageNet, was fine-tuned to classify a cohort of 20 patients (11 benign and 9 malignant cases). Following annotation of tumor regions, the whole-slide images (WSIs) were fragmented into smaller patches (224 × 224 pixels). These patches were non-randomly divided into training (308,843 patches), validation (43,268 patches), and test (42,061 patches) subsets, maintaining a 78:11:11 ratio. The CNN training was caried out for 75 epochs utilizing a batch size of 4, the Adam optimizer, and a learning rate of 0.00001. RESULTS: ResNet50 achieved an accuracy of 98.97%, precision of 99.91%, sensitivity of 97.98%, specificity of 99.91%, F1 score of 98.94%, and AUC of 0.99. CONCLUSIONS: The ResNet50 model developed exhibited high accuracy during training and robust generalization capabilities in unseen data, indicating nearly flawless performance in distinguishing between benign and malignant myofibroblastic tumors, despite the small sample size. The excellent performance of the AI model in separating such histologically similar classes could be attributed to its ability to identify hidden discriminative features, as well as to use a wide range of features and benefit from proper data preprocessing.

Head and Neck Cancer in Pan-American Notable People: An International Survey.

Background: The study of notable people as advocates for raising cancer awareness began in the latter decades of the 20th century. This research aimed to identify Pan-American notable people with head and neck cancer (HNC) and to explore senior health professionals' perspectives on communicating stories of notable patients with HNC to promote prevention. Method: A cross-sectional survey was conducted using an online questionnaire designed in REDCap and administered to 32 senior health professionals with long-standing academic and clinical backgrounds in HNC. In addition, a structured literature review was performed on PubMed, Scopus, EMBASE, Web of Science, LILACS, and gray literature. Results: 18 notable figures were successfully identified from the survey, and 24 from the literature review. These individuals came from the United States, Brazil, Argentina, Mexico, El Salvador, Chile, Colombia, and Peru, and were recognized primarily for their performances as actors, artists, musicians, and athletes. The professionals' outlooks were positive, with 31 (96.9%) agreeing that disseminating these stories can contribute to reducing risk behaviors. Furthermore, all participants (100%) agreed that such stories can promote early detection of HNC, primarily through social media, followed by the internet, and television. Conclusions: The study identified notable individuals and gathered positive perspectives from professionals. Our results suggest that notable people could serve as potential advocates for HNC prevention. Further research is warranted to explore the potential of this prevention strategy.

Mapping oral medicine (stomatology) & oral and maxillofacial pathology international organizations: a scoping review of global data and historical analysis.

OBJECTIVES: To describe the historical evolution and dissemination of the Oral Medicine and Oral and Maxillofacial Pathology international societies and associations across the globe, and to provide insights into their significant contributions toward oral health promotion. STUDY DESIGN: This review was conducted in accordance with the JBI Scoping Review Methodology Group guidance. The reporting followed the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). RESULTS: Search strategy was applied to 5 databases (MEDLINE/PubMed, Scopus, Embase, Web of Science, Latin American and Caribbean Health Sciences (LILACS)) and grey literature (Google Scholar, Open Grey and ProQuest), as well as additional sources, such as organization websites. Eighty-nine sources were included in this review. Forty-six professional associations/societies were identified, of which 39 represented a country or geopolitical region, 2 represented continents, 2 represented multinational organizations and 3 multinational study groups. CONCLUSIONS: Documentation of the historical establishment and development of Oral Medicine and Oral and Maxillofacial Pathology organizations worldwide is limited and describing these processes remains challenging. Analysis of global data reveals heterogeneous development and distribution, resulting in disparities in accessibility and standardization. Further efforts toward oral health promotion should be implemented.

Disruption of oncogenic pathways in mucoepidermoid carcinoma: CREB inhibitor 666.15 as a potential therapeutic agent.

OBJECTIVES: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour with around 50 % of cases carrying the CRTC1-MAML2 translocation. The CREB pathway has been associated with the transforming activity of this translocation. The aim of this study was to determine the effects of CREB inhibition on MEC cell behaviour in vitro. MATERIAL AND METHODS: Two translocation-positive (UM-HMC-2 and H292) and one translocation-negative (H253) MEC cell lines were treated with 666.15, a CREB inhibitor. Drug IC50 doses were determined for each cell line. Clonogenic and spheroid assays were used to assess survival, including percentage of cancer stem cells, and transwell and scratch assays evaluated invasive and migratory capacities, respectively. Immunofluorescence staining was used to determine E-cadherin expression. RESULTS: CREB inhibition significantly reduced the number of surviving colonies and spheroids and delayed cell invasion in all cell lines, but this was more significant in the fusion positive, UM-HMC-2 cells. The expression of E-cadherin was significantly higher in treated UM-HMC-2 and H292 cells. CONCLUSION: CREB inhibition with 666.15 impaired key MEC oncogenic behaviours associated with metastasis and drug resistance, including cell invasion and survival.

Clinicopathological and immunohistochemical aspects of conventional and unicystic canalicular adenoma: a case series.

OBJECTIVE: To describe a well-documented series of 10 new cases of conventional and unicystic canalicular adenoma (CAD). STUDY DESIGN: This was a retrospective study in which the original hematoxylin and eosin and immunohistochemical slides of all cases of CAD diagnosed between 2014 and 2024 were re-evaluated. Clinical data regarding age, gender, clinical presentation, evolution time, and related symptoms were retrieved from the patients' medical records. RESULTS: Ten CADs were identified. Most patients were female (n = 6), with a mean age of 61.2 years. Most tumors presented as a solitary asymptomatic nodule, particularly on the upper lip (n = 7), and two patients reported slight pain or sensitivity. All tumors were well-delimited with a connective tissue capsule. A bosselated or lobulated appearance and cystic formation were observed in all cases. Other features were also observed, such as solid areas, clear cells, beading, morules, and pseudostratification. Eight cases were classified as conventional and two as unicystic. All cases were positive for CK7, S100 protein, and SOX10, while negative for p40 and p63. CONCLUSIONS: This paper described 10 additional cases of CAD, with classic and uncommon microscopic findings, including unicystic. We highlighted the importance of an immunohistochemical panel in differentiating CAD from other salivary gland tumors.

Calcifying Odontogenic Cyst Presenting Odontogenic Keratocyst-Like Areas: A Rare Case Report.

An 81-year-old male patient presented with a well-demarcated, unilocular radiolucent lesion in the right mandibular body, identified during a routine radiographic examination. Based on the clinical hypothesis of a residual cyst, enucleation with curettage was performed, and the specimen was submitted for histopathological analysis. Microscopically, the cystic lesion was predominantly lined by ameloblastomatous epithelium with numerous ghost cells and dentinoid. Additionally, other cystic cavities lined by stratified squamous epithelium with corrugated parakeratin were observed in the fibrous capsule. Based on these features, a final diagnosis of a calcifying odontogenic cyst with odontogenic keratocyst-like areas was established. No recurrence was observed over a 9-year follow-up period. The association of a calcifying odontogenic cyst with odontogenic keratocyst or odontogenic keratocyst-like areas is very rare. To date, this is the second case report in the literature presenting these findings.

Oral manifestations of peripheral T cell lymphoma, not otherwise specified: case series and review of the current literature.

OBJECTIVE: The objective of this study was to describe a series of peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) affecting the oral cavity and to review the available literature. STUDY DESIGN: Cases diagnosed as PTCL-NOS affecting the oral cavity were retrospectively retrieved from pathology files. Original hematoxylin and eosin-stained slides and immunohistochemical reactions were reviewed for microscopic confirmation. The presence of Epstein-Barr virus (EBV) was investigated by in situ hybridization. Clinical and follow-up data were retrieved from patients' pathology and medical files. RESULTS: A total of 5 cases were obtained with a mean age of 51.8 years old, 3 male patients and 2 female patients. Three cases affected the palate and 2 cases affected the gingiva, whereas 1 case affected the maxillary bone. Tumors presented as destructive, infiltrative, and painful lesions causing swelling, ulceration, and tissue necrosis. All cases exhibited CD3 expression. GATA3 was expressed in 3 cases. Four patients were deceased of the disease during follow-up. CONCLUSIONS: PTCL NOS affecting the oral cavity is rare and usually present as a very aggressive disease, associated with a poor prognosis and dismal outcome. (Oral Surg Oral Med Oral Pathol Oral Radiol YEAR;VOL:page range).

Ectomesenchymal Chondromyxoid Tumor of the Anterior Tongue: A Case Image.

Ectomesenchymal chondromyxoid tumor (ECT) is a rare soft tissue tumor with peculiar histogenesis, exhibiting a predilection for the dorsum of the tongue. Molecular evidence suggests that it may originate from the migration of ectomesenchymal pluripotent cells from the neural crest to the tongue, where these cells may eventually proliferate and undergo myxoid and chondroid differentiation. This article illustrates a case of a 16-year-old female patient who presented with a nodule on the dorsum of her tongue, which had been present for four years. Surgical excision was performed, and histopathological analysis revealed a myxoid neoplasia composed of polygonal and spindle cells within a loose stroma containing chondroid areas. Tumor cells were positive for GFAP and S-100 proteins on immunohistochemical study, confirming the diagnosis of ECT. After a 5-year follow-up, the patient has shown no evidence of recurrence. Although rare, ECT can be diagnosed straightforwardly due to its distinctive clinical, histopathological, and immunohistochemical features. Clinicians and pathologists should become familiar with this tumor in order to avoid misdiagnosis.

Pleomorphic adenoma and carcinoma ex-pleomorphic adenoma tumorigenesis: A proteomic analysis.

OBJECTIVES: To conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex-pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry. METHODS: Six normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation. RESULTS: Comparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up-regulated in CXPA compared to PA. Decorin was markedly up-regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA. CONCLUSIONS: Proteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.

Glandular odontogenic cyst misdiagnosed and treated as a periapical inflammatory lesion for 6 years in an older adult.

OBJECTIVES: To document the case of a patient who underwent several endodontic treatments due to a glandular odontogenic cyst misdiagnosed as an inflammatory periapical lesion. BACKGROUND: Glandular odontogenic cysts behave more aggressively, while others have an indolent course. There is limited information on this cyst in the gerodontologic literature. MATERIALS AND METHODS: A 76-year-old male patient presented with an asymptomatic expansive lesion in the anterior mandible resistant to several endodontic treatments. Cone-beam computed tomography revealed a multilocular osteolytic lesion measuring 6.0 × 4.0 cm, with cortical bone perforation. RESULTS: Histopathological analysis of a biopsy specimen was consistent with glandular odontogenic cyst. The patient underwent marginal mandibulectomy with preservation of the base of the mandible. CONCLUSION: A strict diagnostic process is important to avoid unwanted consequences, particularly in the geriatric population.

Histiocytic sarcoma affecting the oral cavity: a clinical, pathologic and molecular study.

OBJECTIVE: To investigate the clinicopathological, immunohistochemical and molecular features of histiocytic sarcomas affecting the oral cavity. METHODS: Pathology files of two institutions were searched for cases of histiocytic sarcoma, and new H&E-stained slides and immunohistochemistry reactions evaluated for diagnosis confirmation. Molecular screening for KRAS and PIK3CA mutations was performed through polymerase chain reaction (PCR) followed by Sanger sequencing. BRAFp.V600E mutation was assessed by pyrosequencing. Clinical data regarding sex, age, tumor location, systemic manifestations, clinical presentation, follow-up time, treatment applied and status at last follow-up were collected from patients' pathology and medical files. RESULTS: Three cases were retrieved during the period investigated (2000-2023). Two females and one male were affected, with a wide age range, involving the tongue, palate and gingiva. Histopathologically, the neoplasms presented as highly pleomorphic atypical cells distributed diffusely with infiltration of normal structures. All cases demonstrated histiocytic differentiation expressing CD68 and CD163, and a high Ki67 expression. Genetic mutations were evaluated in two cases. One case harboured BRAF-V600E mutation, but not in KRAS and PIK3CA, while the second case did not show mutation in BRAF-V600E, KRAS and PI3KCA. One patient was lost, and two patients died after eight and four months of follow-up. CONCLUSION: Histiocytic sarcomas involving the oral cavity are extremely rare, and may represent dissemination of a systemic condition. It has an aggressive biological behaviour with a poor overall prognosis.

Histopathological risk assessment in multisite epithelial dysplasia: A meta-analysis.

OBJECTIVE: Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes. METHODS: The review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design. RESULTS: Forty-six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta-analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia. CONCLUSIONS: No significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.

Atypical cellular neurothekeoma of the oral mucosa: A rare case report and literature review.

Cellular neurothekeoma (CN) is a benign dermal neoplasm that most often affects the head and neck region and rarely occurs in the oral mucosa. We report a rare case of CN with atypical features on the floor of the mouth and summarize the reported cases of oral CN in English-language literature. A 62-year-old woman presented with a 6-month history of a painless mass on the floor of the mouth. Histopathological analysis of the excised specimen revealed a proliferation of neoplastic cells with oval to spindle morphology arranged in a vaguely nested and multinodular architecture separated by scarce hyaline collagen within a predominantly myxoid-rich stroma. The tumor cells were positive for NSE, and CD63 (NKI/C3), and negative for S100 protein, CD34, and SMA. Thus, the final diagnosis was CN. In addition, we summarized all clinicopathological data on oral CNs reported in the English-language literature. Nineteen cases were reviewed. Among them, only one case affected the floor of the mouth of a young girl, in contrast to the present case that occurred in an elderly woman. CN is particularly rare in this location and may be a diagnostic challenge for oral pathologists due to its rarity and morphological similarity with other lesions.

Clinicopathological Features of 26 Intraoral Polymorphous Adenocarcinomas from a Single Brazilian Institution.

PURPOSE: This study describes a large, well-documented case series of salivary gland polymorphous adenocarcinomas (PAC) from a single Brazilian center. METHODS: Demographic data, clinical presentation, histopathological and immunohistochemical features from 26 cases of PAC were analyzed and discussed in detail. RESULTS: Most patients were females (n = 21), with a ratio of 1:4.2 (male: female) with a mean age of 58.8 years (ranging from 36 to 84 years). The most common clinical presentation was a fibrocollagenous, firm nodular lesion, with a mean size of 2.46 cm (ranging from 0.5 to 3 cm). Most lesions occurred on the palate (n = 16), followed by buccal mucosa (n = 3), upper lip (n = 3), buccal vestibule (n = 2) and alveolar ridge (n = 1). Histologically, various growth patterns were observed, including tubular, solid, cribriform, papillary, and cystic. Additionally, glomeruloid slit-like structures, mucous, and clear cells were noted. Surface papillary epithelial hyperplasia was observed in a few cases. Nine cases exhibited myxoid and collagenous areas, while two cases showed fusiform areas and another case demonstrated squamous differentiation. Clear cell predominance was noted in two cases, and peri- and intraneural invasion was seen in eight cases. Immunohistochemical analysis revealed positivity for S-100, p63 and CK7, and negativity for p40 in all cases. The Ki-67 proliferation index was markedly low in most cases, with a mean of 2.5%. CONCLUSION: We have provided a broad, detailed description of the clinical and microscopic features of PAC in a large, Brazilian cohort. These findings, in a resource-limited area, may be quite useful for establishing a proper diagnosis.