Targeted therapies in ameloblastomas and amelobastic carcinoma-A systematic review.

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.

Pediatric Gnathic Bony and Mesenchymal Tumors.

Evaluation of bone pathology within the head and neck region, particularly the gnathic bonesis is complex, demonstrating unique pathologic processes. In part, this variation is due to odontogenesis and the embryological cells that may be involved, which can contribute to disease development and histologic variability. As with any boney pathosis, the key is to have clinical correlation, particularly with radiographic imaging prior to establishing a definitive diagnosis. This review will cover those entities that have a predilection for the pediatric population, and while it is not all inclusive, it should serve as a foundation for the pathologist who is evaluating bony lesions involving the craniofacial skeleton.

Pediatric Odontogenic Tumors.

Odontogenic tumors are rare tumors of the jaws that arise from remnants of the tooth forming apparatus. Some odontogenic tumors demonstrate strong predilection for pediatric patients including the unicystic ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma, ameloblastic fibro-odontoma, odontoma, and primordial odontogenic tumor. In this review, we discuss the clinical, radiographic, histopathologic, and molecular characteristics of select odontogenic tumors that demonstrate pediatric predilection and review management.

A rare primordial odontogenic tumor in a pediatric patient.

Primordial odontogenic tumor (POT) is a rare, benign pediatric lesion that was first included in the 2017 edition of WHO Classification of Head and Neck Tumours. At that point, only 7 cases had been described in the literature; a total of 23 cases have been reported to date. This case report adds to that total by describing a case of POT in a 12-year-old girl and reviews the characteristics of this neoplasm in order to better characterize its clinical, radiographic, and histologic features and increase dentists' awareness of POT. The presence of calcifications within the lesion was reported in 4 of 23 previous cases, and calcifications were also observed in the current case. The presence of calcifications in POT is uncommon and may make radiographic diagnosis more challenging. Treatment of POT is simple excision, and recurrence after excision is rare. Accurate diagnosis is essential, as there has been at least 1 report of overtreatment involving mandibulectomy.

Recurrent oral ulceration: Etiology, classification, management, and diagnostic algorithm.

Recurrent oral ulcerations are manifestations of a heterogeneous set of both general and more-or-less specific oral diseases due to numerous potential etiologies, including, but not limited to, infections, medications, autoimmune disease, and other systemic disease. This review discusses the pathogenesis, clinical presentation, diagnosis, and management of the common causes of recurrent oral ulceration. The following types/etiologies of recurrent oral ulceration are covered: traumatic ulceration, chemical ulceration, recurrent aphthous stomatitis, medication-related ulceration, infectious ulceration, mucocutaneous disease, and autoimmune/systemic disease. A diagnostic algorithm for recurrent oral ulceration is also presented.

Analytic survey of 57 cases of oral metastases.

BACKGROUND: Oral lesions have been reported among the first signs of an undiagnosed metastatic disease. Accurate diagnosis of an occult metastasis remains critical in determining the treatment course. Previous studies regarding oral metastatic tumors present varied data regarding the most frequent metastases to the oral cavity. These discrepancies echo the changes in incidence rates for certain malignancies over time and demonstrate the need for periodic updates in oral metastasis studies. METHODS: Using Text Information Extraction System, a de-identified pathology database, we compiled 57 cases over a period of 19 years using key terms to search for oral metastases. RESULTS: For both males and females, the most common primary sites were lung (21.1%), liver (12.3%), breast (10.5%), kidney (10.5%), and colorectal (8.8%). We found an equal number of lung and breast metastases in females and metastases from the liver to be the most prevalent for males. In most of our cases (54.9%), the patient had no history of the primary malignancy and the oral lesion preceded awareness of the widespread cancer. CONCLUSIONS: As a departure from many previous case series, we found lung and breast metastases to be equally numerous in women and liver as the most common oral metastasis in men. Also, we identified a tendency for the patient to present with a previous history in certain malignancies, such as breast cancer, whereas in other malignancies, such as renal cell carcinoma, our data demonstrated a propensity to present in the oral cavity without history of a primary tumor.

A subset of ectomesenchymal chondromyxoid tumours of the tongue show EWSR1 rearrangements and are genetically linked to soft tissue myoepithelial neoplasms: a study of 11 cases.

AIMS: Ectomesenchymal chondromyxoid tumour (ECT) is a rare, benign intraoral neoplasm showing a predilection for the anterior dorsum of the tongue. The World Health Organization includes ECT in the pathological spectrum of soft tissue myoepithelioma. EWS RNA-binding protein 1 gene (EWSR1) rearrangement is found in 45% of cutaneous, soft tissue and bone myoepithelial neoplasms, and pleomorphic adenoma gene 1 (PLAG1) aberrations are found in 37% of EWSR1-negative soft tissue myoepitheliomas. The aim of this study was to evaluate the presence of EWSR1 and PLAG1 rearrangements in ECTs. METHODS AND RESULTS: Eleven formalin-fixed, paraffin-embedded ECTs were evaluated with fluorescence in-situ hybridization probes for EWSR1 (22q12) and PLAG1 (8q12). Among the 11 ECTs tested, three (27.3%) showed EWSR1 rearrangement in >15% of tumour cells, whereas eight (72.7%) cases did not show EWSR1 rearrangement. Eight of nine (89%) ECTs showed gain of EWSR1, probably representing gain of all or part of chromosome 22, in a varying proportion of neoplastic cells ranging between 1.4% and 27.9%. PLAG1 rearrangement was not detected in the successfully hybridized tissue sections (7/11). No correlation was observed between the molecular and histopathological findings, such as morphology of the neoplastic cells, the presence of atypia, and matrical type. CONCLUSIONS: We identified EWSR1 rearrangement in >25% of ECTs. These results suggest that some ECTs are at least genetically related to myoepithelioma of the soft parts. Finally, PLAG1 aberrations do not appear to be critical in the pathogenesis of ECT of the tongue.

Cervicofacial subcutaneous emphysema: a clinical case and review of the literature.

Cervicofacial subcutaneous emphysema is a known, rare complication of both dental and surgical procedures. Cervicofacial subcutaneous emphysema arises when air is forced beneath the tissues, leading to swelling, crepitus on palpation, and the potential of the air to spread along the fascial planes. This report presents a case of cervicofacial subcutaneous emphysema in a patient who had undergone surgical extraction of the mandibular right first molar. The dentist in this case used a compressed air-driven handpiece to section the tooth. This forced air, under high pressure, into the subcutaneous tissue spaces. The patient presented with severe hemifacial swelling and crepitus on palpation. Computed tomographic examination revealed air subcutaneously, and a diagnosis of cervicofacial subcutaneous emphysema was made.

Ameloblastic carcinoma of the mandible manifesting as an infected odontogenic cyst.

Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor. Although most ACs appear to originate de novo, some cases originate from a pre-existing ameloblastoma. This article presents the case of a 69-year-old man with an AC in the left body of the mandible. Radiographically, the lesion resembled an odontogenic cyst surrounding an impacted tooth. While ACs tend to have aggressive features that distinguish them from their benign counterparts, some are more subtle in their presentation. Therefore, it is important that dentists rule out malignancy in lesions that do not display obvious radiographic features.

Mixed radiopaque and radiolucent lesion of the maxillary sinus: a radiographic challenge.

This article describes 3 patients, each of whom presented with an asymptomatic mixed radiopaque and radiolucent lesion of the maxillary sinus associated with a nonvital tooth. Based on the radiographic findings, a diagnosis of a collapsed (ruptured) radicular cyst was rendered in each case. A tissue biopsy was performed in 1 case, and the results supported the diagnosis. The radiographic and histopathological features, etiology, pathophysiology, and radiographic differential diagnosis of this condition are discussed.

Seven Cases of Proliferative Verrucous Leukoplakia: The Need for a High Clinical Suspicion Among Dental Practitioners.

Proliferative verrucous leukoplakia is a distinct precancerous condition with a high rate of recurrence and malignant transformation over time. Proliferative verrucous leukoplakia has no specific histopathologic presentation; therefore, emphases must be on clinical presentation and history to make a diagnosis giving the need for a high clinical suspicion. This condition is very important for the general dentist to recognize. Here we describe the clinical and microscopic features of seven cases of proliferative verrucous leukoplakia, with two cases which demonstrated malignant transformation (hybrid carcinoma and squamous cell carcinoma).

Osseous dysplasia (cemento-osseous dysplasia) of the jaw bones in western Pennsylvania patients: analysis of 35 cases.

OBJECTIVES: The purpose of this study is to analyze the demographic, clinical, and radiographic presentations of osseous dysplasia of the jaws in western Pennsylvania patients and its associated complications. MATERIALS AND METHODS: The clinical records and radiographs of patients diagnosed with osseous (cement-osseous) dysplasia were retrieved from the electronic health record of the University of Pittsburgh, School of Dental Medicine from 2007 to 2012. All cases were reviewed; the WHO criteria and classification for osseous dysplasia was used. Clinical and demographic data, radiographic findings, and final diagnoses were collected and analyzed. RESULTS: 35 cases of osseous dysplasia were retrieved over the six-year period.The majority (33) were females [94.3%], with ages ranging from 26 to 89 years, with a mean age of 53.9 years +/- standard deviation of 15.6 years, 32 [91.4%] were African Americans and 3 [8.6%] were Caucasians. 17 [48.6%] were florid osseous dysplasia, 13 [37.1%] periapical osseous dysplasia and 5 [14.3%] focal osseous dysplasia. Of the 35 patients only 8 [22.9%] patients were symptomatic. All florid osseous dysplasia patients were African American females, with 7 of the patients being symptomatic and the commonest symptom being pain. Also, all periapical osseous dysplasia patients were African Americans (12 females and 1 male), with 1 of the patients presenting with widening of the diastema. Of the focal osseous dysplasia patients, 3 were Caucasians and 2 African American (4 females and 1 male). CONCLUSION: The cases occurred mostly in African American females with a peak incidence in the fifth and sixth decades of life; most cases occurred in the mandible. The commonest form of osseous dysplasias was the florid osseous dysplasia which is most likely to present with symptoms.

Odontogenic Carcinosarcoma: Clinicopathologic and Molecular Features of Three Cases, a Literature Review and Nomenclature Proposal.

BACKGROUND: Odontogenic carcinosarcoma (OCS) is a rare odontogenic malignancy with limited characterization and unexplored molecular features. We report clinicopathologic and molecular findings in 3 additional OCS and review the literature. METHODS: 3 OCS (5.1%) were identified among 59 malignant odontogenic tumors (in our archives from 1992 to 2022). Clinical, radiologic, histopathologic, immunophenotypic, and molecular findings were reviewed. Data from prior case reports and systematic or non-systematic reviews were extracted for analysis. RESULTS: Three mandibular OCS (age range: 66 to 72 years; 1 male, 2 females) were identified. Case 1 had novel clear-cell morphology, multiple recurrences, and a lethal outcome 28 months after resection. EWSR1 rearrangements were negative, but the tumor showed focal nuclear ß-catenin and strong LEF-1 immunoreactivity. Case 2 demonstrated ameloblastic and sclerosing features and encased the inferior alveolar nerve; the patient was disease-free 22 months after resection with adjuvant chemoradiation therapy. LEF-1 was again strongly positive, and next-generation sequencing demonstrated 9p region-(CDKN2A, CDKN2B) copy number loss, and 12q region-(MDM2, CDK4) copy number gain. Case 3 showed clear-cell and markedly sclerosing features; no follow-up information was available. Literature review along with the current cases yielded 20 cases. OCS showed a male predilection (1.5:1), mandibular predominance (80%, typically posterior), and a bimodal age distribution (modes: 27.7 years, 62.7 years). OCS presented as masses (100%), often with pain (55%), and paresthesia (45%). Tumors were typically radiolucent (88.9%), with bone destruction (61.1%), and/or tooth effacement (27.8%). Preoperative biopsy was sensitive for malignancy (85.7%). At least 45% show evidence for a precursor lesion. 3-year DSS and DFS were 58% and 35%, respectively. Regional and distant (usually lung) metastatic rates were 25% and 31.3%, respectively. Increased mitotic rates and presence of tumor necrosis trended toward worse DSS and DFS. CONCLUSION: OCS is a rare but aggressive malignancy, often arising from precursor tumors and may represent a terminal phenotype rather than a distinct entity. We describe novel clear-cell and sclerosing morphologies. Wnt pathway alterations appear important. Mitotic rates and necrosis may be adverse prognosticators. In keeping with nomenclature trends in other sites, OCS may be more appropriately designated as "biphasic sarcomatoid odontogenic carcinomas."

Acute cervicofacial necrotizing fasciitis: three clinical cases and a review of the current literature.

Cervicofacial necrotizing fasciitis (NF) is a rare condition that can quickly become life-threatening if appropriate treatment is delayed. This condition is observed as a rapidly progressive infection that causes extensive necrosis of the superficial fascia. This report presents a case of cervicofacial NF with microbiological isolation of methicillin-resistant Staphylococcus aureus in a patient with a history of uncontrolled diabetes mellitus following a minor scalp trauma. The article also presents two cases of NF secondary to odontogenic infection. The radiographic finding of the presence of gas locules in the facial planes on the CT scan helped to confirm the diagnosis. Patients were treated with broad-spectrum antibiotic therapy, extensive surgical drainage, debridement, and supportive care. Awareness in the dental community of the signs of NF will facilitate optimal patient management.

Automated detection of premalignant oral lesions on whole slide images using convolutional neural networks.

INTRODUCTION: Oral epithelial dysplasia (OED) is a precursor lesion to oral squamous cell carcinoma, a disease with a reported overall survival rate of 56 percent across all stages. Accurate detection of OED is critical as progression to oral cancer can be impeded with complete excision of premalignant lesions. However, previous research has demonstrated that the task of grading of OED, even when performed by highly trained experts, is subject to high rates of reader variability and misdiagnosis. Thus, our study aims to develop a convolutional neural network (CNN) model that can identify regions suspicious for OED whole-slide pathology images. METHODS: During model development, we optimized key training hyperparameters including loss function on 112 pathologist annotated cases between the training and validation sets. Then, we compared OED segmentation and classification metrics between two well-established CNN architectures for medical imaging, DeepLabv3+ and UNet++. To further assess generalizability, we assessed case-level performance of a held-out test set of 44 whole-slide images. RESULTS: DeepLabv3+ outperformed UNet++ in overall accuracy, precision, and segmentation metrics in a 4-fold cross validation study. When applied to the held-out test set, our best performing DeepLabv3+ model achieved an overall accuracy and F1-Score of 93.3 percent and 90.9 percent, respectively. CONCLUSION: The present study trained and implemented a CNN-based deep learning model for identification and segmentation of oral epithelial dysplasia (OED) with reasonable success. Computer assisted detection was shown to be feasible in detecting premalignant/precancerous oral lesions, laying groundwork for eventual clinical implementation.

Odontogenic and Developmental Oral Lesions in Pediatric Patients.

This article reviews odontogenic and developmental oral lesions encountered in the gnathic region of pediatric patients. The process of odontogenesis is discussed as it is essential to understanding the pathogenesis of odontogenic tumors. The clinical presentation, microscopic features, and prognosis are addressed for odontogenic lesions in the neonate (dental lamina cysts/gingival cysts of the newborn, congenital (granular cell) epulis of the newborn, melanotic neuroectodermal tumor, choristoma/heterotopia, cysts of foregut origin), lesions associated with unerupted/erupting teeth (hyperplastic dental follicle, eruption cyst, dentigerous cyst, odontogenic keratocyst/keratocystic odonogenic tumor, buccal bifurcation cyst/inflammatory collateral cyst) and pediatric odontogenic hamartomas and tumors (odontoma, ameloblastic fibroma, ameloblastoma, adenomatoid odontogenic tumor, primordial odontogenic tumor). Pediatric odontogenic and developmental oral lesions range from common to rare, but familiarity with these entities is essential due to the varying management implications of these diagnoses.

Oral Manifestations of Syphilis: a Review of the Clinical and Histopathologic Characteristics of a Reemerging Entity with Report of 19 New Cases.

BACKGROUND: Syphilis is a sexually-transmitted infectious disease caused by Treponema pallidum. Cases of primary and secondary syphilis are on the rise in the United States, with a 14.4% increase in new cases noted from 2017 to 2018 and an escalation of 71% between the years 2014 and 2018. Fulfilling its nickname of "the great imitator," oral manifestations of syphilis may mimic a variety of infectious, neoplastic, or immune-mediated processes, both clinically and histopathologically. This large spectrum of appearances can create a diagnostic challenge to the clinician and/or pathologist, leading to delay in diagnosis or misdiagnosis. METHODS: A database of oral syphilis cases was created from archives at the University of Kentucky, University of Pittsburgh, LIJMC, Columbia University MC, and University of Tennessee. The age, sex, race, location, duration, and clinical description were recorded. Cases without positive reaction upon immunohistochemistry or serologic tests were excluded. RESULTS: We identified 19 new cases of oral syphilis (17 males, one female, and one case unknown sex) and described the clinical and histopathological features of this re-emerging and potentially fatal disease. All cases demonstrated dense lymphoplasmacytic inflammation, often with inflammatory exocytosis or ulceration at the surface, and perivascular inflammation. CONCLUSIONS: Early recognition of the histopathologic and clinical manifestations of oral syphilis is imperative for prompt diagnosis, improved patient outcomes, and disease prevention.