Adenomatoid odontogenic tumor (AOT) is a relatively rare, asymptomatic benign tumor of tooth-bearing sites of the jaw that preferentially affects younger females. Radiographically, this lesion typically appears as a well-circumscribed, somewhat teardrop-shaped radiolucency containing an embedded tooth, most often a permanent maxillary canine, with occasional clusters of calcific aggregates and surrounded by a corticated border. Histopathologic findings demonstrate rosettes, duct-like structures, and focal areas of calcification. This article presents 2 cases of AOT associated with impacted maxillary premolars.

OBJECTIVE:This report describes an unusual case of a lateral periodontal cyst (LPC) residing between the roots of a mandibular first and second molar. BACKGROUND:The LPC is a developmental odontogenic cyst, the majority situated along the lateral roots of the mandibular canines and premolars. The occurrence of an LPC solely confined to the molar region is extremely rare. Limited information regarding the LPC has appeared in the geriatric literature. PATIENT PRESENTATION:A unilocular cyst-like lesion was incidentally discovered on extraoral and intraoral radiographic examinations involving a 68-year-old patient. It was initially considered an infected odontogenic keratocyst or unicystic ameloblastoma. RESULTS:Histologic examination of the excised specimen revealed a thin cuboidal epithelial lining with focal nodular thickenings and underlying fibrovascular connective tissue wall. The lesion was diagnosed as an LPC. At a 6-month follow-up, the patient has remained asymptomatic and exhibited radiographic osseous regeneration. CONCLUSIONS:The LPC should be added to the differential diagnosis of developmental odontogenic cysts found in the inter-molar region. A preoperative cone beam computed tomography scan may be helpful to optimise the surgical approach. Timely removal of any suspected cystic lesion, particularly in the context of infection in an older patient, may reduce postoperative sequelae and rule out malignancy.

Introduction Noonan syndrome (NS) is an autosomal dominant condition caused by overactivation in the RAS/MAP kinase cell signaling pathway and designated as a type of RASopathy. NS is associated with mutations in PTPN11 in ∼50% of cases. NS is clinically characterized by congenital heart defects, cryptorchidism, short stature, hypertelorism, down-slanting palpebral fissures, low-set ears, neck webbing, and pectus excavatum. Gnathic bone manifestations are rare, but when present are usually reported as multiple giant cell lesions. The purpose of this abstract is to report a previously unreported manifestation of fibroblastic osteosarcoma in a patient with NS. Case Report A 28-year-old male with a history of NS presented with recent onset mandibular swelling and pain. On examination, pronounced anterior mandibular swelling extraorally with intraoral buccal expansion was observed. Panoramic radiograph demonstrated an ill-defined expansile radiolucent lesion with areas of erosive changes within the inferior cortical border of the affected left anterior mandible at the junction of the hardware and bone. An incisional biopsy demonstrated a predominantly sarcomatous spindle cell population associated with foci of malignant osteoid matrix. Malignant-appearing cartilage was featured within lace-like osteoid. Scattered atypical mitoses and neoplastic pleomorphic cells invaded the bone. Isolated features of aneurysmal bone cyst and giant cell granuloma were also featured. The diagnosis of osteosarcoma was supported by high SATB2, CDK4, and Ki-67 (∼80%) immunohistochemical positive staining. Although some areas featured chondroblastic osteosarcoma, the predominant pattern was of a fibroblastic osteosarcoma. The patient subsequently underwent resection with negative surgical margins, all regional lymph nodes were negative. Of note, several previous biopsies were read as aneurysmal bone cyst or fibrous dysplasia. Conclusion This case, which is the first reported case of a fibroblastic osteosarcoma in a patient with NS, expands the spectrum of the disease and draws importance to ongoing surveillance of the gnathic bones in NS.

Introduction Tumors of the head and neck that exhibit rhabdomyoblastic differentiation include rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, spindle cell carcinoma (SpCC), malignant peripheral nerve sheath tumor, or metastatic disease. Spindle cell carcinoma (SpCC) is a rare subtype of squamous cell carcinoma (SCC) typically seen in the oral cavity and larynx. Cases with ulcerated surface epithelium completely devoid of surface dysplastic epithelium that present entirely of a spindle cell proliferation can pose a diagnostic challenge. Additionally, immunohistochemistry (IHC) can demonstrate evidence of differentiation to variable mesenchymal components. Here we present a poorly differentiated SpCC with rhabdomyoblastic differentiation as evidenced by positivity for the rhabdomyoblastic biomarker MyoD-1. Case Presentation A 54-year-old female presented to her dentist with a nodular mass on the anterior mandibular gingiva mimicking a pyogenic granuloma. Upon histopathological examination, H&E tissue sections showed an ulcerated mass devoted of any surface epithelium with malignant spindle cells invading the connective tissue. The spindle cells showed several malignant criteria including pleomorphism, hyperchromatism, increased nuclear-to-cytoplasmic ratio, and atypical mitotic figures. They were arranged in short interlacing fascicles. Abundant eosinophilic cytoplasm with rhabdomyoblastic differentiation was featured. Initial IHC analysis showed diffuse positivity for Myo-D1, focal positivity for Desmin, and negativity for Myogenin, SMA, h-Caldesmon. However, Pancytokeratin, was diffusely positive confirming the diagnosis of SpCC. Other cytokeratins, p53, p63, p40, TLE-1, CD99, and neural markers were all negative. Surgical management at the University of Maryland Medical Center included composite mandibulectomy and bilateral neck dissection, followed by adjuvant radiotherapy and chemotherapy. Surgical pathology findings were positive for perineural invasion, negative for all lymph nodes and tissue margins. Conclusion This case highlights the challenge in diagnosing cases of SpCC devoid of surface epithelium. Pathologists should also be aware of the possibility of rhabdomyoblastic differentiation in SpCC and cautiously interpret skeletal muscle biomarkers given the variable expression patterns.

Introduction Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy worldwide. MEC can be categorized histologically into low, intermediate, and high-grade tumor. When the epidermoid component predominates, MEC may mimic oral squamous cell carcinoma (OSCC) which contribute to diagnostic challenge. Meticulous evaluation would be warranted to differentiate between moderate or high-grade MEC and OSCC. Differentiating these two entities is necessary to prognosticate survival and to determine the most appropriate treatment plan. Case Presentation A 20-year female presented with painless lesion, persisted for 1-2 years, and hasn’t changed in size for last 6 months. Clinical examination showed 1.5 × 0.5 cm elevated lesion of posterior hard palate with central ulcerated area. Incisional biopsy demonstrated evidence of proliferating tumor islands some of which were connected to overlying surface epithelium. That consisted of predominantly epidermoid cells, with scattered mucinous component. Small cystic islands lined by mucous, intermediate, and epidermoid cells, that contributed to less than 20% of tumor were noted. Mucicarmine and PAS-diastase positive highlighted scattered mucous cells. Tumor cells were p63 positive, and negative for Calponin and GATA-3. Findings were consistent with MEC, low grade. Upon excision, surgical impression included erosion of underlying bone. Excisional biopsy showed tumor infiltration of terminal duct and overlying surface epithelium and more prominent cystic component. S100 highlighted perineural invasion. Final diagnosis of MEC, low grade, according to AFIP classification criteria was rendered. Conclusion MEC arising from terminal duct ending in surface epithelium, might be erroneously interpreted as OSCC, especially when predominated with epidermoid cells on small incisional biopsies. Extensive tumor sampling, demonstration of intracellular mucin assisted by special stains, and presence of intermediate cells, represent important clue to diagnosis. It is important to use the most objective histopathologic features to grade MEC and to determine prognosis or treatment modality more accurately.

OBJECTIVES/GOALS: Our aim is to establish soluble salivary biomarkers indicative of increased risk of oral premalignancy to be used in a point-of-service technology. Our goal is to non-invasively assess risk level for premalignancy by characterizing a molecular signature pattern that can be applied to such a diagnostic tool at routine dental or medical visits. METHODS/STUDY POPULATION: Adult patients 18 years of age and older who are non-smokers and patients of the University of Maryland School of Dentistry Oral Medicine Clinic and have been diagnosed with oral premalignancy (proliferative verrucous leukoplakia) are eligible. Exclusion criteria include history of immunosuppression or immune compromise; use of antifungal, antibiotic, and/or antiviral medications within the past three months; and gross dental disease. Serial unstimulated saliva samples will be collected at baseline or diagnosis of oral premalignancy, 6 months and 12 months. Solubility testing will be completed to determine whether malignant markers such as EGFR/mTOR/PI3K/p53 are soluble in saliva, and patient samples will be analyzed by ELISA and compared to appropriate controls. RESULTS/ANTICIPATED RESULTS: We anticipate demonstrating increased activity of molecular pathways known to be involved in malignant transformation, such as EGFR/mTOR/PI3K/p53, or increased burden of select microbial pathogens to be associated with increased risk of oral premalignancy in the form of proliferative verrucous leukoplakia. Preliminary sensitivity and specificity testing of the identified markers will provide additional insight to the utility of a diagnostic tool with salivary specimen. Therefore, the microbiome and/or molecular profile proposed from these results will serve as a translational application to development of future point-of-service test devices to be used in the prevention and detection of oral premalignant lesions. DISCUSSION/SIGNIFICANCE: Oral cancer is the sixth most common cancer worldwide, and presents challenges in its diagnosis and clinical management. Later diagnosis is associated with poorer patient outcomes—therefore, a molecular and microbiome profile that may be used in a noninvasive diagnostic test technology would prove beneficial to providers and patients.

Oral nodular chronic hyperplastic candidiasis (CHC) is a rare subset of oral CHC, a relatively uncommon condition associated with immunosuppression. We present a case of a 73-year-old female with nodular CHC of the tongue and a medical history noted for type 2 diabetes. Additionally, we discuss the diagnosis, management, and conditions potentially associated with oral nodular CHC.

BackgroundCancer's hallmark feature is its ability to evolve, leading to metastasis and recurrence. Although genetic mutations and epigenetic changes have been implicated, they don't fully explain the leukocytic traits that many cancers develop. Cell fusion between cancer and somatic cells, particularly macrophages, has been suggested as an alternative pathway for cancer cells to obtain new traits by acquiring exogenous genetic material.MethodsThis study aims to investigate the potential biological outcomes of tumor-myeloid cell fusion by generating tumor-macrophage hybrid cells. Two clones with markedly different tumorigenicity were selected, and RNA-seq was used to compare their RNA expressions with that of the control cells. Based on the results that the hybrid cells showed differential activation in several upstream regulator pathways that impact their biological behaviors, the hybrid cells' abilities to recruit stromal cells and establish angiogenesis as well as their cell cycle distributions were investigated through in vitro and in vivo studies.ResultsAlthough both hybrid clones demonstrated p53 activation and reduced growth rates, they exhibited distinct cell cycle distributions and ability to grow in vivo. Notably, while one clone was highly tumorigenic, the other showed little tumorigenicity. Despite these differences, both hybrid clones were potent environmental modifiers, exhibiting significant abilities to recruit stromal and immune cells and establish angiogenesis.ConclusionsThe study revealed that tumor-somatic cell fusion is a potent environmental modifier that can modulate tumor survival and evolution, despite its relatively low occurrence. These findings suggest that tumor-somatic cell fusion could be a promising target for developing new cancer therapies. Furthermore, this study provides an experimental animal platform to investigate cancer-myeloid fusion and highlights the potential role of tumor-somatic cell fusion in modulating the tumor environment.

AIM:To review published cases and case series of the peripheral odontogenic keratocyst (POKC) of the gingiva, report an unusual presentation, and discuss lesional recurrence. MATERIALS AND METHODS:A search of the English language literature for gingival OKCs was conducted. The inclusion of new case yielded a database containing 29 affected patients. Clinical, surgical, radiographic, and histopathologic findings have been summarized. RESULTS:With available patient demographics, 62.5% were female and 37.5% were male, with an overall mean age at diagnosis of 53.8 years. There was near-equal lesional affinity for the jaws, of which 44.0% occurred in the posterior region, 32.0% anteriorly, and 24.0% overlapped these areas. Twenty-five percent of lesions had a normal color, 30.0% appeared yellow, 20.0% were white, and 10.0% were blue. The majority of lesions were < 1 cm and nearly 42% manifested exudation or fluctuance. Lesional pain was infrequent. Pressure resorption was recorded in 45.8% of cases. Most lesions were managed with conservative surgical modalities. Follow-up information was available in 16 primary cases, of which 5 recurred, signifying a 31.3% recurrence rate, including the featured case, which recurred twice. CONCLUSION:To reduce recurrence of a gingival OKC, supraperiosteal dissection is advocated. Further, it is advised to follow POKCs for 5-7 years postoperatively, remaining vigilant for subtle clinical manifestations of recurrence. Timely discovery and excision of a POKC of the gingiva may decrease the incidence of a mucogingival defect.

OBJECTIVES/GOALS: This study aims to develop objectively scored histological characteristics of early oral leukoplakia, which may be correlated with molecular pathways predictive of progression into proliferative verrucous leukoplakia (PVL). The secondary aim is to develop a biomarker profile to be used in diagnosis, staging, and management of PVL. METHODS/STUDY POPULATION: Clinical and pathology records of 120 patients with oral leukoplakia and/or PVL were reviewed. Eight patients were selected—all had serial biopsies over time leading to PVL suspicion. Specimens were deidentified and subjected to blinded examination by a board certified oral pathologist, then scored relative to the extent of each of the commonly accepted histologic characteristics of PVL: hyperkeratosis, acanthosis, blunt rete ridges, hyperchromatic nuclei, increased nuclear-cytoplasmic ratio, dyskeratosis, and surface corrugation. Given these results, a larger subset of patient samples will be labeled and assayed for expression of epidermal growth factor receptor tyrosine kinases and downstream pro-oncogenic signaling mediators. Expression of these factors will be tested against progression to PVL. RESULTS/ANTICIPATED RESULTS: Histologically, in scoring the specimens from eight subjects, the characteristics of acanthosis, dyskeratosis, and blunted rete ridges had the strongest correlation with eventual progression to PVL. These criteria will therefore be recommended as an objective histopathologic method of identification of patients with high risk of development of PVL, and therefore malignant potential. We expect the results of the biomarker assay to provide a molecular basis for predicting PVL pathogenesis. Particularly, we anticipate pro-oncogenic targets such as EGFR, PI3K, Akt, and mTOR pathways will show increased expression as leukoplakic lesions progress. These results would then provide the basis for testing patient samples for expression of these markers in a longitudinal study of PVL emergence and progression. DISCUSSION/SIGNIFICANCE: The aggressive nature of PVL, with a rate of malignant transformation of 61% and mortality rate of 40%, requires close clinical monitoring in order to improve patient outcomes. Therefore, well defined objective clinical, histologic, and molecular criteria are critical for early detection of sites likely to progress to PVL and subsequent malignancy.

Ghost cell odontogenic carcinoma (GCOC) is a rare malignant tumor of odontogenic origin, with only about 50 cases reported in the English literature so far. Histologically, it is characterized by ghost cells, dentinoid deposits, high grade malignant cellular features, and areas of necrosis and invasion. Having common histological features with other odontogenic ghost cell lesions (OGCL) like calcifying odontogenic cyst (COC) and dentinogenic ghost cell tumors, it is crucial to recognize GCOC malignant features, as it can be destructive and invasive, sometimes showing distant metastases and high recurrence rate. For this reason, it may entail more aggressive surgical approach and multimodal therapeutic regimen. Here we present a case report of GCOC arising in a previous COC, treated with surgical excision that showed persistence and recurrence after two years. The clinical and histological features of this rare occurrence are presented, in addition to the surgical approach, and a summary of literature review of OGCL.

AbstractBackgroundConsidering that early detection of squamous cell carcinoma (SCC) improves prognosis and clinical examination is the primary detection method, we identified factors related to the clinical evaluation of oral mucosal lesions. Due to the growing role of telehealth, our study was based on clinical image evaluation.Subjects and MethodsOral medicine specialists and dental students evaluated six images of benign, potentially malignant, or SCC lesions (18 images in total). We analyzed the role of personal factors of the examiners and the visual pathological features of the lesion upon which the participants based their evaluation.ResultsOne hundred thirty‐three subjects participated. Half of the benign images were correctly evaluated. On average 1.2 (±SD1.3) cancer pictures were recognized correctly and 3.66 (±SD1.42) images were considered potentially malignant. Potentially malignant lesions were correctly evaluated at an average of 4.08 (±SD1.48) images. For cancer and potentially malignant lesion images, there were significantly better results among clinicians with the worst results from the fourth‐year students. Student results correlated significantly with years of study, number of weeks spent in the oral medicine clinic, and interest in oral pathology. Consideration of lesion irregularity yielded a correct diagnosis, whereas wrong answers were based on color changes. Lesion size and margins were considered equally important.ConclusionsUsing clinical images as part of the diagnostic process provides good results, though increased clinical experience for graduates and undergraduates may be necessary to improve accuracy. Therefore, emphasizing the important visual parameters of malignancy may be valuable in the current telehealth era.

Abstract The trademark of cancer is the ability to evolve, which lays the grounds for progressive events such as metastasis and recurrence. Although genetic mutations and epigenetic changes have been implicated as the mechanisms, they don’t explain why many cancers develop leukocytic traits. Cell fusion between cancer and somatic cells, particularly macrophages, has been suggested as an alternative pathway for cancer cells to obtain new traits via acquiring exogenous genetic material. In this study, tumor-macrophage hybrid cells were generated, and two clones, both grew slowly yet with very different tumorigenicity, were selected for further study. Despite their very different abilities to form tumors in mice, both clones showed significant abilities to influence the tumor microenvironment. RNA-seq of the hybrid cell clones revealed the differential expression profiles of the hybrid cells that contributed to the biological behaviors. This study emphasizes the role of hybrid cells as potent environmental modifiers that aid tumor survival and evolution despite their minority status among the tumor cells. This study also provides an animal experimental platform to study cancer-myeloid fusion and a potential direction for novel therapeutic interventions.