The impact and outcomes of cancer-macrophage fusion.

BACKGROUND: Cancer'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. METHODS: This 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. RESULTS: Although 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. CONCLUSIONS: The 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.

Recurrent peripheral odontogenic keratocyst: Review of the literature and presentation of a novel case initially masquerading as an atypical infected lateral periodontal cyst.

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.

Factors important in the correct evaluation of oral high-risk lesions during the telehealth era.

BACKGROUND: Considering 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 METHODS: Oral 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. RESULTS: One 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. CONCLUSIONS: Using 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.

Ghost Cell Odontogenic Carcinoma Arising in a Previous Calcifying Odontogenic Cyst: A Case Report and Review of Literature.

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.

Immunohistochemical profile of the anti-apoptosis, apoptosis and proliferation markers Bcl-2, caspase-3, p53, and Ki-67 in botryoid odontogenic cysts compared to lateral periodontal cysts and gingival cysts of the adult.

We investigated the differences in growth and rates of recurrence of the botryoid odontogenic cyst (BOC) and the less aggressive lateral periodontal cyst (LPC) and gingival cyst of the adult (GCA). We compared the immunohistochemical expression of selected biomarkers of apoptosis and proliferation and of regulators of their activity. Sections from archival paraffin blocks of 15 BOCs, six GCAs, six LPCs, and three odontogenic keratocysts (OKCs) were processed for immunohistochemical localization of Bcl-2, caspase-3, p53 and Ki-67. Labeled and unlabeled epithelial cells were counted and differences in the mean labeling index (LI) were evaluated statistically. The only significant differences in LI were for the anti-apoptotic marker, Bcl-2; the hierarchy was BOC > OKC > LPC > GCA. In two BOCs, 97% of the cells, and in all OKCs, all of the basal cells were labeled with Bcl-2. Otherwise, cells labeled with Bcl-2, p53 and caspase-3 were scattered among the basal and intermediate epithelial cell layers. Ki-67 labeled almost exclusively basal cells in the BOCs, LPCs and GCAs, and both basal and intermediate layer cells in the OKCs. Our findings suggest that while there was no significant difference in replicative potential of the GCAs, LPCs and BOCs, factors that influence apoptosis may be partially responsible for the more aggressive behavior of BOCs and OKCs.

The use of artificial intelligence, machine learning and deep learning in oncologic histopathology.

BACKGROUND: Recently, there has been a momentous drive to apply advanced artificial intelligence (AI) technologies to diagnostic medicine. The introduction of AI has provided vast new opportunities to improve health care and has introduced a new wave of heightened precision in oncologic pathology. The impact of AI on oncologic pathology has now become apparent, and its use with respect to oral oncology is still in the nascent stage. DISCUSSION: A foundational overview of AI classification systems used in medicine and a review of common terminology used in machine learning and computational pathology will be presented. This paper provides a focused review on the recent advances in AI and deep learning in oncologic histopathology and oral oncology. In addition, specific emphasis on recent studies that have applied these technologies to oral cancer prognostication will also be discussed. CONCLUSION: Machine and deep learning methods designed to enhance prognostication of oral cancer have been proposed with much of the work focused on prediction models on patient survival and locoregional recurrences in patients with oral squamous cell carcinomas (OSCC). Few studies have explored machine learning methods on OSCC digital histopathologic images. It is evident that further research at the whole slide image level is needed and future collaborations with computer scientists may progress the field of oral oncology.

Retraction Note to: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression.

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article. The published image labelled "VEGF + VEGFR-2 shRNA" has a metadata label of S4d-plexinB1 shRNA2". In Figure 2E, statistical significance was shown in the published figure for four comparisons, but upon recalculation, one comparison noted as significant was not. In Figure 6A, the lower left image is labelled "VEGF shRNA" in the published figure, but the metadata label is "S4DshRNA-HN121-20X". In Figure 6C, specifically, within columns 2-4, for each antibody used for immunocytochemistry, the three images have been swapped so that the original images do not match the shRNA labels in the figure (the labels for the two antibodies were correct). In Figure 7D, the first published image is labelled as "IgG" in the paper, but the metadata show a label of "Restore (V+S).tif". The third published image has a label of "anti-VEGF IgG", and the metadata show a label of "con sh.tif". Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

High resolution monitoring of chemotherapeutic agent potency in cancer cells using a CMOS capacitance biosensor.

Monitoring cell viability and proliferation in real-time provides a more comprehensive picture of the changes cells undergo during their lifecycle than can be achieved using traditional end-point assays. Particularly for drug screening applications, high-temporal resolution cell viability data could inform decisions on drug application protocols that might lead to better treatment outcomes. We describe a CMOS biosensor that monitors cell viability through high-resolution capacitance measurements of cell adhesion quality. The system consists of a 3 × 3 mm2 chip with an array of 16 sensors, on-chip digitization, and serial data output that can be interfaced with inexpensive off-the-shelf components. An imaging system was developed to provide ground-truth data of cell coverage concurrently with data recordings. Results showed the sensor's ability to detect single-cell binding events, track cell morphology changes, and monitor cell motility. A chemotherapeutic assay was conducted to examine dose-dependent cytotoxic effects on drug-resistant and drug-sensitive cancer cell lines. Concentrations higher than 5 µM elicited cytotoxic effects on both cell lines, while a dose of 1 µM allowed discrimination of the two cell types. The system demonstrates the use of real-time capacitance measurements as a proof-of-concept tool that has potential to hasten the drug development process.

Combination Nivolumab/Ipilimumab Immunotherapy For Melanoma With Subsequent Unexpected Cardiac Arrest: A Case Report and Review of Literature.

The success of immunotherapy in the treatment of patients with advanced melanoma has paved the way for unprecedented successes in the treatment of many other malignancies. We present a case of extensively metastatic oral mucosal melanoma that responded successfully to combined immune checkpoint blockade with ipilimumab and nivolumab but developed multiple immune-related adverse events, including myocarditis, a rare event associated with immunotherapy of elderly melanoma patients. Though the acute myocarditis was managed successfully, the patient succumbed to sudden cardiac death. This case highlights the fact, that autoimmune carditis must be considered when working up the sudden onset of shortness of breath in patients on immune checkpoint blockade. After controlling the acute myocarditis with high-dose steroids, which should be tapered over 6 weeks, further cardiology care is needed, and a defibrillator might have to be implanted. Understanding the pathophysiology of immune-related adverse events could make cancer immunotherapy both more effective and safer.

Gingival squamous cell carcinoma: an unexpected clincal presentation.

Squamous cell carcinoma (SCC) is an aggressive tumor and represents the most common oral malignancy found by dental health care providers. Timely detection is paramount to reduce patient comorbidities of regional and distant metastases and improve survival rates. To augment recognition of early stage of gingival SCC (GSCC), this article features the somewhat innocuous clinical findings in a 60-year-old female.

Computer-assisted analysis of immunohistological parameters in oral giant cell granulomas.

OBJECTIVE: The aim of this study was to examine the relationship between active osteoclasts, as defined by positive nuclear NFATc1 signals, and the clinical behaviors of oral giant cell granulomas. MATERIALS AND METHODS: NFATc1 immunohistochemical and TRAP-Cbfa1 double immunofluorescence stainings were performed on 9 cases of peripheral giant cell granulomas (PGCGs), 9 cases of central giant cell granulomas (CGCGs) with a recurrent history, and 10 cases of CGCGs without a recurrent history. The results were photographed and quantified by ImageJ. Nine osteoclast- and osteoblast-related parameters were analyzed with conventional statistics and with Rapidminer, an open data analysis platform for computer predictive modeling. RESULTS: Peripheral giant cell granulomas had a significantly lower percentage of active osteoclasts than CGCGs. The recurrent CGCG subgroup had the highest active osteoclast density in comparison with non-recurrent CGCG subgroup and PCCGs. CONCLUSIONS: The study strongly indicates that the status of osteoclasts, as defined by the subcellular NFATc1 signal, has an association with the clinical behavior of oral giant cell granulomas. NFATc1 staining may be useful as a biomarker to predict recurrence of CGCGs. The study also illustrates the potential application of data science tools in studying pathology to facilitate the discovery of disease-associated biomarkers.

Real-Time Measurements of Cell Proliferation Using a Lab-on-CMOS Capacitance Sensor Array.

We describe a capacitance sensor array that has been incorporated into a lab-on-CMOS system for applications in monitoring cell viability. This paper presents analytical models, calibration results, and measured experimental results of the biosensor. The sensor has been characterized and exhibits a sensitivity of 590 kHz/fF. We report results from benchtop tests and in vitro experiments demonstrating on-chip tracking of cell adhesion as well as monitoring of cell viability. Human ovarian cancer cells were cultured on chip, and measured capacitance responses were validated by comparison with images from photomicrographs of the chip surface. Analysis was performed to quantify cell proliferation and adhesion, and responses to live cells were estimated to be 100 aF/cell.

Central xanthoma of the mandible associated with hyperlipidemia: A rare presentation.

Xanthoma is a common, self-limiting cutaneous lesion of non-Langerhans cell, lipid-laden foamy histiocytes that is often concomitant with hyperlipidemia. The intraosseous counterpart is rarely encountered and typically presents as a painless, expansile osteolytic process in the context of hyperlipidemia or normolipidemia. Only a scant number of gnathic xanthomas have been reported in the otolaryngologic literature. We report the clinical, laboratory, radiographic, histopathologic, immunohistochemical, and ultrastructural studies of a mandibular lesion discovered in an asymptomatic 16-year-old male, and associated with 2 previously unreported comorbidities, namely hyperlipidemia and vitamin D deficiency.

Juvenile Trabecular Ossifying Fibroma.

Benign fibro-osseous lesions within the maxillofacial region represent a heterogeneous group of benign entities with overlapping histologic features. Ossifying fibroma, the rarest of these entities, represents a true neoplasm. Juvenile ossifying fibroma (JOF) is considered an aggressive rapidly growing sub-type. It tends to occur in the first or second decades of life. Based on histological and clinical features it can further be classified into two variants, namely juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). JTOF features a proliferation of cellular fibroblastic tissue admixed with woven bone trabeculae with varying histologic presentations. Correlation with clinical and radiographic features is essential to differentiate it from other fibro-osseous lesions. A case of JTOF of the mandible is exemplified in this Sine Qua Non Radiology-Pathology article.

Large Cell Transformation of Oral Mycosis Fungoides.

Mycosis fungoides (MF) accounts for approximately 50% of all primary cutaneous lymphomas. MF occurrence in the oral cavity is extremely rare with approximately 45 cases reported to date. We present a case of a 68 year-old man with a raised nodular lesion of the ventral tongue with clinical impression of irritational fibroma. Histopathologic and immunohistochemical (IHC) examination revealed a phenotype consistent with MF with large cell transformation in the context of Sezary syndrome. The histological diagnosis of oral MF requires a high index of suspicion and IHC panel to rule out large cell transformation. To our knowledge, only four cases of large cell transformation of oral MF have been reported in the English literature. The clinical and histopathologic features of a rare case of intra-oral MF with large cell transformation are exemplified in this article.

Recurrent Gingival Squamous Papilloma: A Rare Finding in a Child.

Gingival squamous papilloma (SP) is a mucocutanous, benign proliferation rarely seen in the pediatric population. The majority of publications of affected younger patients have been confined to datasets from clinicopathologic investigations. A limited number of case reports in this age group have appeared in the literature, usually featuring primary gingival lesions. Recognition of recurrent gingival SPs in pediatric patients has been underappreciated. The purpose of this report is to present the case of a four-year-old boy with a gingival SP that recurred twice within 18 months and to increase awareness of this entity in children.

Emergent gingival cyst of the adult.

The gingival cyst of the adult is a relatively rare, benign odontogenic cyst that maintains an insidious growth rate. This article describes a case of a diminutive fibrotic overgrowth arising on the labial interproximal gingiva between the mandibular right canine and first premolar in a 68-year-old woman. Within 1 year, the lesion had increased in size and appeared vesicular. The morphologic changes warranted surgical excision and histopathologic review. The lesion was diagnosed as a gingival cyst. At a 4.5-month recall appointment, there was no evidence of recurrence. Early lesional detection can potentially mitigate mucogingival defects and improve clinical outcomes.

Angiopoietin-2 is expressed in oral Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) persists today as a highly prevalent vascular cancer, often found in HIV patients. Studies have shown that angiopoietin 2 (Ang2), a pro-angiogenic protein, is involved in the pathogenesis of this tumor. However, expression of this protein has not been investigated in oral KS lesions. Thus, we aimed to investigate the expression of Ang2 in samples of oral KS. METHODS: Immunohistochemistry was used to evaluate Ang2 expression in 14 oral KS cases, with degrees of expression being analyzed in a semi-quantitative manner. In addition, clinical information such as age, gender, race, tumor location, size, color, and appearance, as well as HIV status, was collected and included in the analysis. RESULTS: All patients were white males, mostly HIV-positive, with a mean age of 40 years. Clinically, the lesions were dark red/blue/purple masses, ranging from 1 to 2.5 cm in diameter, found in various locations such as the tongue, palate, and gingiva. Expression of Ang2 was noted in 72% (10/14) of the samples. Of these, 10% showed weak expression, 60% moderate, and 30% strong expression. CONCLUSIONS: Our results indicate that Ang2 is expressed in oral KS and, consistent with results from previous studies, show that Ang2 may contribute to the pathogenesis of this lesion.

Glycogen-Rich Clear Cell Squamous Cell Carcinoma Originating in the Oral Cavity.

Clear cell squamous cell carcinoma (CCSCC) is a rare histological subtype of squamous cell carcinoma (SCC) that was originally described in the skin. Here, we report a case of a 66-year-old female patient who presented with a fungating ulcerative mass of the left lateral tongue extending anteriorly to the floor of the mouth, and posteriorly to the left retromolar fossa and the oropharynx. The patient had a history of SCC of the left posterior tongue that was treated with partial glossectomy and adjuvant radiotherapy. Representative biopsies were obtained from the floor of the mouth, tongue and retromolar fossa. The examined biopsies showed various degrees of dysplastic surface epithelium with transition into infiltrating epithelial tumor nests and cords with clear cytoplasm and malignant cellular features. Pancytokeratin, CK5/6, and p63 were all diffusely positive. S-100, Calponin, and smooth muscle actin (SMA) were negative. PAS stain was diffusely positive and diastase labile in the tumor clear cells. Sparse areas of mucicarmine positivity were noted. Based on these findings a final diagnosis of a glycogen-rich CCSCC was given. This case represents a very rare histological variant of oral SCC, which is significant for the histological differential diagnosis of clear cell tumors of the oral cavity.