Metastasising ameloblastoma or ameloblastic carcinoma? A case report with mutation analyses.

BACKGROUND: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis. CASE PRESENTATION: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet. CONCLUSIONS: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses.

HPV and RAD51 as Prognostic Factors for Survival in Inoperable Oral and Oropharyngeal Cancer in Patients Unfit for Chemotherapy Treated with Hyperfractionated Radiotherapy.

INTRODUCTION: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. OBJECTIVE: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. METHOD: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. RESULTS: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. CONCLUSION: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Negative pressure therapy in the orofacial region in oncological patients - two case reports.

BACKGROUND: Chronic wounds and their problematic healing is a widely discussed topic in all branches of medicine. In recent years, vacuum therapy appears to be a very successful non-invasive method supporting the healing of these wounds. The aim of this paper is to demonstrate the possibility of utilizing a vacuum system in the orofacial area where other conservative and surgical procedures have failed. CASES: The case reports demonstrate the use of vacuum therapy in non-healing postoperative wounds in cancer patients. CONCLUSION: Vacuum therapy has limited use in the orofacial area, but based on our experience, we can conclude that it has a very positive effect on the healing of chronic wounds. Thanks to this treatment, it was possible to reduce the frequency of dressings and significantly shorten the length of hospital stay. Despite these advantages, however, it is necessary to adhere to the conditions for the application of vacuum treatment.

Detecting Binocular Diplopia in Orbital Floor Blowout Fractures: Superiority of the Orthoptic Approach.

Background and Objectives: In patients with orbital floor blowout fracture (OFBF), accurate diagnosis of ocular motility disorder is important for decisions about conservative or surgical therapy. However, the accuracy of the traditional test for detecting binocular diplopia/ocular motility disorder using a moving pencil or finger (hereinafter, "finger test") has been generally accepted as correct and has not been subject to scrutiny so far. Hence, its accuracy relative to full orthoptic examination is unknown. Materials and Methods: In this paper, the results of the "finger test" were compared with those derived from a complex examination by orthoptic tests (considered "true" value in patients with OFBF). Results: "Finger test" detected ocular motility disorder in 23% of patients while the full orthoptic examination proved much more efficient, detecting ocular motility disorder in 65% of patients. Lancaster screen test and test with color filters were the most important tests in the battery of the orthoptic tests, capable of identifying 97.7% and 95.3% of patients with ocular motility disorder, respectively. Still, none of the tests were able to correctly detect all patients with ocular motility disorder in itself. Conclusions: As the presence of ocular motility disorder/binocular diplopia is an important indication criterion for the surgical solution of the orbital floor blowout fracture, we conclude that a complex orthoptic evaluation should be always performed in these patients.

Oral Appliance Effectiveness and Patient Satisfaction with Obstructive Sleep Apnea Treatment in Adults.

BACKGROUND Indication of oral appliances for the treatment of an obstructive sleep apnea (OSA) includes both patients with primary snoring and mild OSA, as well as patients with moderate to severe OSA who refuse other treatment or in whom such treatment failed. The aim of this study was to verify the effectiveness of current OSA treatment by objective measurements, and to assess by means of a questionnaire patients' satisfaction with oral appliances manufactured in our laboratory. MATERIAL AND METHODS The study enrolled 58 adult patients (40 men, 18 women) with mean age of 50.5 years; most were overweight or had class I obesity; mean baseline apnea-hypopnea index (AHI) value prior to the beginning of treatment was 31.3, range 0.6-71. RESULTS Average AHI reduction in the entire group was 10.4; 31% of patients experienced AHI reduction by at least 50%. Significant AHI reduction was proven when using the appliance. Appliances affect the reduction of AHI and patients tolerate the appliances well. CONCLUSIONS Oral appliances complement positive-pressure treatment and do not interfere with it in any way. Craniometric parameters seem to be applicable as predictors of success or failure of appliance treatment.

Buccal films as a dressing for the treatment of aphthous lesions.

BACKGROUND: Buccal flexible films in the form of solid, thin, mucoadhesive patches can be used as dressings separating aphthous lesions from the environment of the oral cavity, which can in turn shorten the treatment period and reduce the pain perception. METHODS: The clinical study was performed on 36 volunteers suffering from aphthous lesions. The first group was treated using standard means-by application of an oral gel containing cholin salicylate (Mundisal) on the aphthous lesion. The second group was treated with the same preparation; however, the lesion was covered with a mucoadhesive film following the application of the gel. The criteria for statistical evaluation were the size of lesions in relation to the length of the treatment and the subjective perception of the treatment results. RESULTS AND CONCLUSIONS: The application of buccal films covering aphthous lesions during the treatment significantly increased the rate of healing when compared with the standard methods of treatment. While the pain improvement was statistically significant as soon as Day 3 in the experimental group, it was only apparent on Day 5 in the control group, and the number of successfully treated patients (pain perception improving to visual analogue scale 2 or less) was at all time points higher in the experimental group than in the control group. The results imply that the use of buccal films for treatment of aphthous lesions is very promising and can lead to a significant reduction in the duration of patients' discomfort.

Age-related changes in the tooth-bone interface area of acrodont dentition in the chameleon.

Chameleon teeth develop as individual structures at a distance from the developing jaw bone during the pre-hatching period and also partially during the post-hatching period. However, in the adult, all teeth are fused together and tightly attached to the jaw bone by mineralized attachment tissue to form one functional unit. Tooth to bone as well as tooth to tooth attachments are so firm that if injury to the oral cavity occurs, several neighbouring teeth and pieces of jaw can be broken off. We analysed age-related changes in chameleon acrodont dentition, where ankylosis represents a physiological condition, whereas in mammals, ankylosis only occurs in a pathological context. The changes in hard-tissue morphology and mineral composition leading to this fusion were analysed. For this purpose, the lower jaws of chameleons were investigated using X-ray micro-computed tomography, laser-induced breakdown spectroscopy and microprobe analysis. For a long time, the dental pulp cavity remained connected with neighbouring teeth and also to the underlying bone marrow cavity. Then, a progressive filling of the dental pulp cavity by a mineralized matrix occurred, and a complex network of non-mineralized channels remained. The size of these unmineralized channels progressively decreased until they completely disappeared, and the dental pulp cavity was filled by a mineralized matrix over time. Moreover, the distribution of calcium, phosphorus and magnesium showed distinct patterns in the different regions of the tooth-bone interface, with a significant progression of mineralization in dentin as well as in the supporting bone. In conclusion, tooth-bone fusion in chameleons results from an enhanced production of mineralized tissue during post-hatching development. Uncovering the developmental processes underlying these outcomes and performing comparative studies is necessary to better understand physiological ankylosis; for that purpose, the chameleon can serve as a useful model species.

Novel PAX9 gene polymorphisms and mutations and susceptibility to tooth agenesis in the Czech population.

OBJECTIVES: Tooth agenesis is one of the most common developmental anomalies in humans. Genetic and environmental factors may be of etiological importance in this condition. Among genes involved in tooth morphogenesis, mutations in PAX9, MSX1, AXIN2, WNT10a, and EDA genes have been associated with tooth agenesis. The aim of our study was to investigate the relationship between the PAX9 gene variants and tooth agenesis in the Czech population. METHODS: The selected regions of the PAX9 gene were analysed by direct sequencing and compared with the reference sequence from the GenBank online database (NCBI). RESULTS: We found several novel variants in the PAX9 gene, e.g. insertion g.5100_5101insC (rs11373281) with simultaneous substitution g.5272C>G (rs4904155) in exon 1, and mutation g.10934C>T (Gly203Gly, rs61754301) in exon 3. In subjects with full dentition we observed polymorphisms g.10276A>G (rs12882923) and g.10289A>G (rs12883049) in IVS2 (intervening sequence 2) previously related to tooth agenesis in Polish study. CONCLUSIONS: In our study we excluded a direct effect of rs12882923 and rs12883049 polymorphisms on the dental agenesis in the Czech population. All described PAX9 genetic variants were present both in patients with tooth agenesis and controls. We expect that tooth agenesis in our cohort of patients is caused by mutations in regions different from PAX9 exons analyzed in our study.

Simulation of Orbital Fractures Using Experimental and Mathematical Approaches: A Pilot Study.

This contribution gives basic information about the mechanical behavior of the facial part of the human skull cranium, i.e., the splanchnocranium, associated with external loads and injuries caused mainly by brachial violence. The main areas suffering from such violence include the orbit, frontal, and zygomatic bones. In this paper, as a first approach, brachial violence was simulated via quasi-static compression laboratory tests, in which cadaveric skulls were subjected to a load in a testing machine, increasing till fractures occurred. The test skulls were also used for research into the dynamic behavior, in which experimental and numerical analyses were performed. A relatively high variability in forces inducing the fractures has been observed (143-1403 N). The results lay the basis for applications mainly in forensic science, surgery, and ophthalmology.

High PD-L1 expression on immune cells along with increased density of tumor-infiltrating lymphocytes predicts a favorable survival outcome for patients with loco-regionally advanced head and neck cancer: early results from a prospective study.

Introduction: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment. Methods: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression. Results: Among a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates. Discussion: The early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy. Trial registration: The study is registered with Clinicaltrials.gov. - NCT05941676.

Mucoadhesive films as perspective oral dosage form.

UNLABELLED: Mucoadhesion is a specific phenomenon of creating bonds during intimate contact between biological surfaces covered by a mucus layer and a mucoadhesive material. In recent years come to the forefront of interest in the pharmaceutical industry modern dosage forms based on this specific process. Films (discs, patches) composed of mucoadhesive polymers (cellulose derivatives, polyacrylates, polyoxyethylene, etc.) prepared by established methods (solvent casting, hot melt extrusion, etc.) could be perspective candidates for oral administration of many drugs due to their flexibility and comfortable use. In addition, they can circumvent the relatively short residence time of conventional oral dosage forms on the mucosa and provide a precisely measured drug dose to the application site. Moreover, they can also help to protect the wound surface, thus help to reduce pain and improve effectiveness of the therapy. The aim of this article is to give an overview about the principles of creation of mucoadhesive bonds and about novel dosage form - mucoadhesive films in terms of their composition, preparation and practical usage. KEYWORDS: oral mucosa mucoadhesion principles mucoadhesive dosage forms films patches discs.

Oral mucosa and therapy of recurrent aphthous stomatitis.

UNLABELLED: Oral mucosa is one of the specific surfaces of the human body, which is permanently exposed to external factors related with food intake, breathing and speaking processes, which can lead to the onset of some problems. Disorders of the oral mucosa are a group of diseases, affecting, in the course of life, the majority of the population. Many of the oral mucosa ailments are manifested by lesions. Recurrent aphthous stomatitis (RAS) is the most common of these diseases. Despite much clinical and research attention, its causes remain poorly understood and treatment is only symptomatic. RAS is reported to affect up to 25% of the population worldwide. Topical or systemic therapy (corticosteroids, antiseptics, anti-inflamatory drugs, immunomodulating agents, etc.) can be used for treatment of RAS-associated symptoms. In general, topical therapy should be preferred due to the smaller drug load of the organism. In both cases, the active substance has to be in suitable dosage form. Recently, besides the conventional ways of application (rinses), the main disadvantage of which is the short time of resistance in the oral cavity, mucoadhesive dosage forms are used. The aim of this article is to give a theoretical overview of the oral mucosa topic and its most frequent disease - recurrent aphthous stomatitis in terms of various types of the disease classification, diagnosis and therapy, and in terms of the usage of various types of active substances and medical forms. KEYWORDS: oral mucosa recurrent aphthous stomatitis therapy mucoadhesive dosage forms.

Primary cilia and hypoxia-associated signaling in developmental odontogenic cysts in relation to autosomal dominant polycystic kidney disease - A novel insight.

Developmental cysts are pathological epithelial-lined cavities arising in various organs as a result of systemic or hereditary diseases. Molecular mechanisms involved in the formation of developmental odontogenic cysts (OCs) are not fully understood yet; the cystogenesis of renal cysts originating from the autosomal dominant polycystic kidney disease (ADPKD) has been, however, explored in much greater detail. This narrative review aimed i) to summarize molecular and cellular processes involved in the formation and growth of developmental OCs, especially dentigerous cysts (DCs) and odontogenic keratocysts (OKCs), ii) to find if there are any similarities in their cystogenesis to ADPKD cysts, and, based on that, iii) to suggest potential factors, candidate molecules, and mechanisms that could be involved in the DC formation, thus proposing further research directions. Here we suggest a possible association of developmental OCs with primary cilia disruption and with hypoxia, which have been previously linked with cyst formation in ADPKD patients. This is illustrated on the imagery of tissues from an ADPKD patient (renal cyst) and from developmental OCs, supporting the similarities in cell proliferation, apoptosis, and primary cilia distribution in DC/OKC/ADPKD tissues. Based on all that, we propose a novel hypothesis of OCs formation suggesting a crucial role of mutations associated with the signaling pathways of primary cilia (in particular, Sonic Hedgehog). These can lead to excessive proliferation and formation of cell agglomerates, which is followed by hypoxia-driven apoptosis in the centers of such agglomerates (controlled by molecules such as Hypoxia-inducible factor-1 alpha), leading to cavity formation and, finally, the OCs development. Based on this, we propose future perspectives in the investigation of OC pathogenesis.

Enhancing oral squamous cell carcinoma prediction: the prognostic power of the worst pattern of invasion and the limited impact of molecular resection margins.

Objective: Oral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC. Methods: We performed hierarchical clustering of principal components to identify distinct patterns of tumor growth and their association with patient prognosis. We also used next-generation sequencing to analyze somatic mutations in tumor and marginal tissue samples. Results: Our analyses uncovered that the grade of worst pattern of invasion (WPOI) is strongly associated with depth of invasion and patient survival in multivariable analysis. Mutations were primarily detected in the DNA isolated from tumors, but several mutations were also identified in marginal tissue. In total, we uncovered 29 mutated genes, mainly tumor suppressor genes involved in DNA repair including BRCA genes; however none of these mutations significantly correlated with a higher chance of relapse in our medium-size cohort. Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes. Conclusion: Even histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse.

Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma.

Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell carcinoma (HNSCC) is determined by the degree of invasiveness of the primary tumor and by the extent of metastatic spread into regional and distant lymph nodes. Moreover, the level of the perineural invasion itself associates with tumor localization, invasion's extent, and the presence of nodal metastases. Here, we summarize the current knowledge about different aspects of epigenetic changes, which can be associated with HNSCC while focusing on perineural invasion (PNI). We review epigenetic modifications of the genes involved in the PNI process in HNSCC from the omics perspective and specific epigenetic modifications in OSCC or other neurotropic cancers associated with perineural invasion. Moreover, we summarize DNA methylation status of tumor-suppressor genes, methylation and demethylation enzymes and histone post-translational modifications associated with PNI. The influence of other epigenetic factors on the HNSCC incidence and perineural invasion such as tobacco, alcohol and oral microbiome is overviewed and HPV infection is discussed as an epigenetic factor associated with OSCC and related perineural invasion. Understanding epigenetic regulations of axon growth that lead to tumorous spread or uncovering the molecular control of axon interaction with cancer tissue can help to discover new therapeutic targets for these tumors.

Role of orthoptics and scoring system for orbital floor blowout fracture: surgical or conservative treatment.

AIM: To assess the role of orthoptics in referring patients with orbital floor blowout fracture (OFBF) for conservative or surgical treatment and based on the results, to propose a scoring system for such decision making. METHODS: A retrospective analysis of 69 patients with OFBF was performed (35 treated conservatively, 34 surgically). The role of orthoptics in referring to surgery or conservative treatment was retrospectively evaluated, the factors with the highest significance for decision making were identified, and a scoring system proposed using Logistic regression. RESULTS: According to defined criteria, the treatment was unsuccessful in 2 (6%) surgically treated and only in one (3%) conservatively treated patient. The proposed scoring system includes the defect size and several values resulting from the orthoptic examination, the elevation of the eyebulb measured on Lancaster screen being the most significant. CONCLUSION: The study demonstrates the benefits of orthoptic examination when making decisions on conservative or surgical treatment and for diagnosing ocular motility disorder (with or without binocular diplopia) in OFBF patients. The proposed scoring system could, following verification in a prospective study, become a valuable adjunctive tool.

Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost.

PURPOSE: We evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer. METHODS: Thirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70-72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables-tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4. RESULTS: After a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%). CONCLUSION: The combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

The use of a battery of examination methods for detection of cervical metastases in squamous cell carcinoma of the oral cavity.

INTRODUCTION: In patients with squamous cell carcinoma of the orofacial area, the presence of cervical metastases represents a single most significant prognostic factor. This fact underlines the importance of thorough examination of the cervical lymph nodes for potential tumor involvement. To verify this, the most common investigative methods are physical examination (PE), sonography (US) and computed tomography (CT), which have also been used to assess the stage of the disease in the patients in our research. OBJECTIVE: To evaluate the performance of individual methods (physical examination, sonography, computed tomography) and combinations. METHOD: Patients with squamous cell carcinoma of the oral cavity, who had undergone physical, US and CT examinations at our department followed by radical neck dissection were included in this retrospective study. A total of 57 patients were included. RESULTS: The sensitivity of PE, US and CT were 38%, 69% and 61%, respectively, however CT+US combination yielded 83% sensitivity and combination of all these methods 86% sensitivity. The number of false positives was however relatively high with specificity of the 3-way combination at 65%. CONCLUSION: A combination of our three widely available inexpensive methods detected 86% of metastases in cervical nodes. The large number of false positives however indicates that the method should rather be used for screening in selecting patients who need additional and more expensive imaging than for diagnosing cervical metastases. Also, as 14% of cervical metastases pass undetected using our method, we would recommend an additional examination at least by US+PE several weeks to a few months after the initial examination.

Early morphogenesis of heterodont dentition in minipigs.

The minipig provides an excellent experimental model for tooth morphogenesis because its diphyodont and heterodont dentition resemble that of humans. However, little information is available on the processes of tooth development in the pig. The purpose of this study was to classify the early stages of odontogenesis in minipigs from the initiation of deciduous dentition to the late bell stage when the successional dental lamina begins to develop. To analyze the initiation of teeth anlagens and the structural changes of dental lamina, a three-dimensional (3D) analysis was performed. At the earliest stage, 3D reconstruction revealed a continuous dental lamina along the length of the jaw. Later, the dental lamina exhibited remarkable differences in depth, and the interdental lamina was shorter. The dental lamina grew into the mesenchyme in the lingual direction, and its inclined growth was underlined by asymmetrical cell proliferation. After the primary tooth germ reached the late bell stage, the dental lamina began to disintegrate and fragmentize. Some cells disappeared during the process of lamina degradation, while others remained in small islands known as epithelial pearls. The minipig can therefore, inter alia, be used as a model organism to study the fate of epithelial pearls from their initiation to their contribution to pathological structures, primarily because of the clinical significance of these epithelial rests.

Reawakening of Ancestral Dental Potential as a Mechanism to Explain Dental Pathologies.

During evolution, there has been a trend to reduce both the number of teeth and the location where they are found within the oral cavity. In mammals, the formation of teeth is restricted to a horseshoe band of odontogenic tissue, creating a single dental arch on the top and bottom of the jaw. Additional teeth and structures containing dental tissue, such as odontogenic tumors or cysts, can appear as pathologies. These tooth-like structures can be associated with the normal dentition, appearing within the dental arch, or in nondental areas. The etiology of these pathologies is not well elucidated. Reawakening of the potential to form teeth in different parts of the oral cavity could explain the origin of dental pathologies outside the dental arch, thus such pathologies are a consequence of our evolutionary history. In this review, we look at the changing pattern of tooth formation within the oral cavity during vertebrate evolution, the potential to form additional tooth-like structures in mammals, and discuss how this knowledge shapes our understanding of dental pathologies in humans.