Characterization of stromal calcifications in odontogenic keratocyst: a multicentric study.

Odontogenic keratocysts (OKCs) are locally aggressive cysts that exhibit typical histopathological features and have a propensity for recurrence. Though histological variations are observed in OKCs, hard tissue formation and metaplastic changes are rare, and the underlying pathogenesis is not well understood. This study aimed to characterize stromal calcifications and analyze their association with odontogenic components in non-syndromic and syndrome-associated cases of OKCs. We analyzed 153 cases of OKCs from healthcare institutes in India and Japan. The epithelial and stromal features were evaluated, and the relationship of calcifications with odontogenic rests was determined. Immunohistochemistry for cytokeratin-19 and special stains including Masson Trichrome and Van Gieson, were used for identification of odontogenic rests and calcifications respectively. Stromal calcifications were observed in 29.41% OKCs. The calcification patterns included irregular dystrophic, dentinoid with linear or calcospherite-type mineralization, and psammoma calcifications. Psammoma and dentinoid calcifications were found in the proximity of cytokeratin-19-positive odontogenic rests or satellite cysts, whereas majority cases with dystrophic calcifications did not exhibit co-localization with stromal odontogenic components. Distinct patterns of calcifications were observed in OKCs. Calcifications found in proximity of the odontogenic rests were possibly indicative of an inductive or host-mediated response.

In Silico Analysis of Genes Associated with the Pathogenesis of Odontogenic Keratocyst.

Odontogenic keratocyst (OK) is a benign intraosseous cystic lesion characterized by a parakeratinized stratified squamous epithelial lining with palisade basal cells. It represents 10-12% of odontogenic cysts. The changes in its classification as a tumor or cyst have increased interest in its pathogenesis. OBJECTIVE: Identify key genes in the pathogenesis of sporadic OK through in silico analysis. MATERIALS AND METHODS: The GSE38494 technical sheet on OK was analyzed using GEOR2. Their functional and canonical signaling pathways were enriched in the NIH-DAVID bioinformatic platform. The protein-protein interaction network was constructed by STRING and analyzed with Cytoscape-MCODE software v 3.8.2 (score > 4). Post-enrichment analysis was performed by Cytoscape-ClueGO. RESULTS: A total of 768 differentially expressed genes (DEG) with a fold change (FC) greater than 2 and 469 DEG with an FC less than 2 were identified. In the post-enrichment analysis of upregulated genes, significance was observed in criteria related to the organization of the extracellular matrix, collagen fibers, and endodermal differentiation, while the downregulated genes were related to defensive response mechanisms against viruses and interferon-gamma activation. CONCLUSIONS: Our in silico analysis showed a significant relationship with mechanisms of extracellular matrix organization, interferon-gamma activation, and response to viral infections, which must be validated through molecular assays.

Application of machine learning in the preoperative radiomic diagnosis of ameloblastoma and odontogenic keratocyst based on cone-beam CT.

OBJECTIVES: Preoperative diagnosis of oral ameloblastoma (AME) and odontogenic keratocyst (OKC) has been a challenge in dentistry. This study uses radiomics approaches and machine learning (ML) algorithms to characterize cone-beam CT (CBCT) image features for the preoperative differential diagnosis of AME and OKC and compares ML algorithms to expert radiologists to validate performance. METHODS: We retrospectively collected the data of 326 patients with AME and OKC, where all diagnoses were confirmed by histopathologic tests. A total of 348 features were selected to train six ML models for differential diagnosis by a 5-fold cross-validation. We then compared the performance of ML-based diagnoses to those of radiologists. RESULTS: Among the six ML models, XGBoost was effective in distinguishing AME and OKC in CBCT images, with its classification performance outperforming the other models. The mean precision, recall, accuracy, F1-score, and area under the curve (AUC) were 0.900, 0.807, 0.843, 0.841, and 0.872, respectively. Compared to the diagnostics by radiologists, ML-based radiomic diagnostics performed better. CONCLUSIONS: Radiomic-based ML algorithms allow CBCT images of AME and OKC to be distinguished accurately, facilitating the preoperative differential diagnosis of AME and OKC. ADVANCES IN KNOWLEDGE: ML and radiomic approaches with high-resolution CBCT images provide new insights into the differential diagnosis of AME and OKC.

Differentially expressed extracellular matrix genes functionally separate ameloblastoma from odontogenic keratocyst.

BACKGROUND: Ameloblastoma and odontogenic keratocyst (OKC) are odontogenic tumors that develop from remnants of odontogenic epithelium. Both display locally invasive growth characteristics and high predilection for recurrence after surgical removal. Most ameloblastomas harbor BRAFV600E mutation while OKCs are associated with PATCH1 gene mutation but distinctive indicators of ameloblastoma growth characteristics relative to OKC are still unclear. The aim of this study was to assess hub genes that underlie ameloblastoma growth characteristics using bioinformatic analysis, ameloblastoma samples and mouse xenografts of human epithelial-derived ameloblastoma cells. METHODS: RNA expression profiles were extracted from GSE186489 gene expression dataset acquired from Gene Expression Ominibus (GEO) database. Galaxy and iDEP online analysis tools were used to identify differentially expressed genes that were further characterized by gene ontology (GO) and pathway analysis using ShineyGO. The protein-protein interaction (PPI) network was constructed for significantly upregulated differentially expressed genes using online database STRING. The PPI network visualization was performed using Cytoscape and hub gene identification with cytoHubba. Top ten nodes were selected using maximum neighborhood component, degree and closeness algorithms and analysis of overlap was performed to confirm the hub genes. Epithelial-derived ameloblastoma cells from conventional ameloblastoma were transplanted into immunocompromised mice to recreate ameloblastoma in vivo based on the mouse xenograft model. The top 3 hub genes FN1, COL I and IGF-1 were validated by immunostaining and quantitative analysis of staining intensities to ameloblastoma, OKC samples and mouse ameloblastoma xenografts tissues. RESULTS: Seven hub genes were identified among which FN1, COL1A1/COL1A2 and IGF-1 are associated with extracellular matrix organization, collagen binding, cell adhesion and cell surface interaction. These were further validated by positive immunoreactivity within the stroma of ameloblastoma samples but both ameloblastoma xenograft and OKC displayed only FN1 and IGF-1 immunoreactivity while COL 1 was unreactive. The expression levels of both FN1 and IGF-1 were much lower in OKC relative to ameloblastoma. CONCLUSION: This study further validates a differentially upregulated expression of matrix proteins FN1, COL I and IGF-1 in ameloblastoma relative to OKC. It suggests that differential stromal architecture and growth characteristics of ameloblastoma relative to OKC could be an interplay of differentially upregulated genes in ameloblastoma.

Immunohistochemical expression of SPARC in odontogenic keratocysts: a comparative study with other odontogenic cysts.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been shown to modulate aggressive behavior in several benign and malignant tumors. Little is known about SPARC expression in odontogenic keratocyst (OKC), an odontogenic cyst with an aggressive nature. To the best of our knowledge, only one study has been investigated the expression of this protein in OKCs. This study aimed to characterize SPARC expression in OKCs. Additionally, to determine whether SPARC is associated with aggressive behavior in OKCs, SPARC expression in OKCs was compared with radicular cysts (RCs), dentigerous cysts (DCs) and calcifying odontogenic cysts (COCs). These odontogenic cysts showed no or less aggressive behavior. METHODS: SPARC expression was evaluated in 38 OKCs, 39 RCs, 35 DCs and 14 COCs using immunohistochemistry. The percentages of positive cells and the intensities of immunostaining in the epithelial lining and the cystic wall were evaluated and scored. RESULTS: Generally, OKCs showed similar staining patterns to RCs, DCs and COCs. In the epithelial lining, SPARC was not detected, except for ghost cells in all COCs. In the cystic wall, the majority of positive cells were fibroblasts. Compared between 4 groups of odontogenic cysts, SPARC expression in OKCs was significantly higher than those of RCs (P < 0.001), DCs (P < 0.001) and COCs (P = 0.001). CONCLUSIONS: A significant increase of SPARC expression in OKCs compared with RCs, DCs and COCs suggests that SPARC may play a role in the aggressive behavior of OKCs.

Endodontic microsurgery and prosthodontic treatment of a permanent anterior concrescence: A case report.

Concrescence is a rare dental anomaly in which two adjacent teeth are united only by their cementum. Concrescence most frequently occurs in molars, especially a third mandibular molar and a supernumerary tooth. It is rarely seen in the maxillary anterior teeth. This case report is the first in the literature which details the successful treatment of a concrescence between the maxillary central incisor and a supernumerary tooth through multidisciplinary therapy. The treatment plan included root canal treatment, endodontic microsurgery, and prosthodontic treatment.

Gorlin-Goltz Syndrome - A Rare Case Entity in Young Child.

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, which depicted presence of numerous basal cell carcinoma in conjunction with multiorgan abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the keratocystic odontogenic tumour are usually one of the first manifestations of the syndrome. This article includes a case report of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumour and treatment modalities.

PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.

BACKGROUND: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone. OKCs can be sporadic or associated with nevoid basic cell carcinoma syndrome (NBCCS). However, the factors that initiate OKCs and the mechanism of cyst formation remain unclear. Here, we investigated the impact of PTCH1 and SMO mutations on disease progression, as well as the effects of sonic hedgehog (SHH) signaling pathway inhibitors GDC-0449 and GANT61 on OKC fibroblasts. METHODS: Eight sporadic OKC fibroblasts without gene mutations were used as the control, and six NBCCS-related fibroblasts were cultured in vitro. The effect of PTCH1 non-truncated mutation 3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutation on OKC fibroblast proliferation was examined by EdU assay. CCK8 and wound-healing assays detected the effects of OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations on the proliferation and migration of HaCaT cells after co-culture. Quantitative real-time PCR detected the effects of GDC-0449 or GANT61 on the SHH signaling pathway in NBCCS-related OKCs with PTCH1 truncated mutations and PTCH1 c.3499G>A (p.G1167R) and/or SMO c.2081C>G (p.P694R) mutations. RESULTS: PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) promoted the proliferation of OKC fibroblasts. The proliferation and migration of HaCaT cells were affected by NBCCS-related OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations. GDC-0449 significantly inhibited the SHH signaling pathway in NBCCS-related OKC fibroblasts with PTCH1 truncated mutations. An NBCCS-related OKC carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations were resistant to GDC-0449 but inhibited by GANT61. CONCLUSIONS: Genetic mutations in OKC fibroblasts may affect the biological behavior of epithelial and stromal cells and cause disease. GDC-0449 could be used to treat OKCs, especially NBCCS-related OKCs with PTCH1 truncated mutations. SMO c.2081C>G (p.P694R) may lead to resistance to GDC-0449; however, GANT61 may be used as an alternative inhibitor.

Comprehensive cornified envelope protein profile of odontogenic keratocysts clarifies the characteristics of non-keratinized oral epithelium.

BACKGROUND: Odontogenic keratocysts constitute 10%-20% of odontogenic cysts and exhibit a distinctive corrugated parakeratinized lining epithelium. Considering that cornified envelope formation is an important phenomenon during keratinocyte differentiation, this study aimed to clarify the characteristics of cornified envelope formation in odontogenic keratocysts. METHODS: We investigated the cellular distribution of cornified envelope-related proteins (transglutaminases and their substrates), as well as the upstream regulatory protein c-Fos, by immunohistochemical analysis of the lining epithelium of 20 odontogenic keratocysts. We examined the corresponding mRNA levels by quantitative polymerase chain reaction. Ten dentigerous cysts served as control non-keratinized cysts. RESULTS: The distributions of transglutaminase and their substrates except loricrin and small protein-rich protein 1a significantly differed between odontogenic keratocysts and dentigerous cysts. There was no significant difference in c-Fos expression between odontogenic keratocysts and dentigerous cysts. The mRNA levels of transglutaminases and their substrates were significantly higher in odontogenic keratocysts than in dentigerous cysts. However, c-Fos mRNA levels did not significantly differ between groups. CONCLUSION: Surprisingly, the overall appearance of cornified envelope-related proteins of odontogenic keratocysts was consistent with the characteristics of non-keratinized oral mucosa identified in previous studies. These findings indicate that the contribution of cornified envelope-related molecules in odontogenic keratocysts is similar to that in non-keratinized oral epithelium, rather than keratinized oral epithelium, suggesting that odontogenic keratocysts are not genuine keratinized cysts. The upregulation of cornified envelope-related genes in odontogenic epithelium could be an important pathognomonic event during odontogenic keratocyst development.

Pediatric Oral Pathology: Odontogenic Cysts.

Cysts encountered in the head and neck typically arise from epithelium that would normally be programmed to form teeth or tooth-supporting structures (odontogenic epithelium). These cysts come with a confusing array of similar-sounding names and histopathologic features that are sometimes shared between conditions. Here we describe and contrast the relatively-common lesions: hyperplastic dental follicle, dentigerous cyst, radicular cyst, buccal bifurcation cyst, odontogenic keratocyst, glandular odontogenic cyst, and the less-common gingival cyst of the new-born and thyroglossal duct cyst. The goal of this review is to help clarify and simplify these lesions for the general pathologist, pediatric pathologist, and surgeon.

Identification of Immune Infiltration in Odontogenic Keratocyst by Integrated Bioinformatics Analysis.

BACKGROUND: Odontogenic keratocyst (OKC) is a relatively common odontogenic lesion characterized by local invasion in the maxillary and mandibular bones. In the pathological tissue slices of OKC, immune cell infiltrations are frequently observed. However, the immune cell profile and the molecular mechanism for immune cell infiltration of OKC are still unclear. We aimed to explore the immune cell profile of OKC and to explore the potential pathogenesis for immune cell infiltration in OKC. METHODS: The microarray dataset GSE38494 including OKC and oral mucosa (OM) samples were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in OKC were analyzed by R software. The hub genes of OKC were performed by protein-protein interaction (PPI) network. The differential immune cell infiltration and the potential relationship between immune cell infiltration and the hub genes were performed by single-sample gene set enrichment analysis (ssGSEA). The expression of COL1A1 and COL1A3 were confirmed by immunofluorescence and immunohistochemistry in 17 OKC and 8 OM samples. RESULTS: We detected a total of 402 differentially expressed genes (DEGs), of which 247 were upregulated and 155 were downregulated. DEGs were mainly involved in collagen-containing extracellular matrix pathways, external encapsulating structure organization, and extracellular structure organization. We identified ten hub genes, namely FN1, COL1A1, COL3A1, COL1A2, BGN, POSTN, SPARC, FBN1, COL5A1, and COL5A2. A significant difference was observed in the abundances of eight types of infiltrating immune cells between the OM and OKC groups. Both COL1A1 and COL3A1 exhibited a significant positive correlation with natural killer T cells and memory B cells. Simultaneously, they demonstrated a significant negative correlation with CD56dim natural killer cells, neutrophils, immature dendritic cells, and activated dendritic cells. Immunohistochemistry analysis showed that COL1A1 (P = 0.0131) and COL1A3 (P < 0.001) were significantly elevated in OKC compared with OM. CONCLUSIONS: Our findings provide insights into the pathogenesis of OKC and illuminate the immune microenvironment within these lesions. The key genes, including COL1A1 and COL1A3, may significantly impact the biological processes associated with OKC.

[Application of Deep Learning in Differential Diagnosis of Ameloblastoma and Odontogenic Keratocyst Based on Panoramic Radiographs].

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.

Ameloblastoma modifies tumor microenvironment for enhancing invasiveness by altering collagen alignment.

Tumor progression is profoundly affected by crosstalk between cancer cells and their stroma. In the past decades, the development of bioinformatics and the establishment of organoid model systems have allowed extensive investigation of the relationship between tumor cells and the tumor microenvironment (TME). However, the interaction between tumor cells and the extracellular matrix (ECM) in odontogenic epithelial neoplasms and the ECM remodeling mechanism remain unclear. In the present study, transcriptomic comparison and histopathologic analysis revealed that TME-related genes were upregulated in ameloblastoma compared to in odontogenic keratocysts. Tumoroid analysis indicated that type I collagen is required for ameloblastoma progression. Furthermore, ameloblastoma shows the capacity to remodel the ECM independently of cancer-associated fibroblasts. In conclusion, ameloblastoma-mediated ECM remodeling contributes to the formation of an invasive collagen architecture during tumor progression.

Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC), a newly designated entity of odontogenic cysts, is an intraosseous jaw cyst that is entirely or predominantly lined by orthokeratinized squamous epithelium. The aim of this study was to report a large series of OOC to substantiate its clinicopathologic profiles and to investigate PTCH1 mutations in OOCs. METHOD: The clinicopathologic features of 167 OOCs from 159 patients were analyzed and the immunohistochemical expression of markers related to cell differentiation and proliferation was evaluated. Furthermore, PTCH1 mutations were analyzed in 14 fresh samples of OOC. RESULTS: OOCs occurred mostly in the third and fourth decades (60.4%) with a male predilection (66.7%). The lesions developed more often in the mandible than maxilla, primarily in the posterior mandible and ramus. Eight patients (5.0%) showed multiple locations of either bilateral posterior mandible (n = 6) or both the maxilla and mandible. Radiographically, the majority of OOCs (91.2%) showed a well-demarcated, unilocular radiolucency with 14 multilocular cases (8.8%). A follow-up of 131 patients (123 treated by enucleation with or without marsupialization and eight by peripheral ostectomy) revealed no recurrence during an average period of 4.56 years after surgery. Immunohistochemistry indicated lower proliferative activity and a varying epithelial differentiation pattern in OOC compared with odontogenic keratocysts (OKC). No PTCH1 mutation was detected, except for three known single nucleotide polymorphisms. CONCLUSION: The clinicopathological and molecular differences between OOC and OKC justified their separation, and unlike OKCs, OOCs did not harbor PTCH1 mutations, suggesting different pathogenesis underlying these two jaw cysts.

Decoding a gene expression program that accompanies the phenotype of sporadic and basal cell nevus syndrome-associated odontogenic keratocyst.

BACKGROUND: Odontogenic keratocyst is characterized by local aggressive behavior and a high recurrence rate, as well as its potential to develop in association with the basal cell nevus syndrome. The aim of this study was to decode the gene expression program accompanying odontogenic keratocyst phenotype. METHODS: 150-bp paired-end RNA-sequencing was applied on six sporadic and six basal cell nevus syndrome-associated whole-tissue odontogenic keratocyst samples in comparison to six dental follicles, coupled with bioinformatics and complemented by immunohistochemistry. RESULTS: 2654 and 2427 differentially expressed genes were captured to characterize the transcriptome of sporadic and basal cell nevus syndrome-associated odontogenic keratocysts, respectively. Gene ontologies related to "epidermis/skin development" and "keratinocyte/epidermal cell differentiation" were enriched among the upregulated genes (KRT10, NCCRP1, TP63, GRHL3, SOX21), while "extracellular matrix organization" (ITGA5, LOXL2) and "odontogenesis" (MSX1, LHX8) gene ontologies were overrepresented among the downregulated genes in odontogenic keratocyst. Interestingly, upregulation of various embryonic stem cells markers (EPHA1, SCNN1A) and genes committed in cellular reprogramming (SOX2, KLF4, OVOL1, IRF6, TACSTD2, CDH1) was found in odontogenic keratocyst. These findings were highly shared between sporadic and basal cell nevus syndrome-associated odontogenic keratocysts. Immunohistochemistry verified SOX2, KLF4, OVOL1, IRF6, TACSTD2/TROP2, CDH1/E-cadherin, and p63 expression predominantly in the odontogenic keratocyst suprabasal epithelial layers. CONCLUSION: The odontogenic keratocyst transcriptomic profile is characterized by a prominent epidermal and dental epithelial fate, a repressed dental mesenchyme fate combined with deregulated extracellular matrix organization, and enhanced stemness gene signatures. Thus, we propose a developed epidermis-like phenotype in the odontogenic keratocyst suprabasal epithelial cells, established in parallel to a significant upregulation of marker genes related to embryonic stem cells and cellular reprogramming.

Peripheral odontogenic keratocyst: Clinicopathological and immunohistochemical characterization.

OBJECTIVE: The aim of this study is to present and discuss the salient clinicopathological features, differential diagnosis and epithelial immunohistochemical profile of three additional cases of peripheral odontogenic keratocyst (POKC) and to present a review of the literature. POKC is a locally aggressive odontogenic lesion. The peripheral variant of the odontogenic keratocyst is rare and more frequently located in anterior gingiva. MATERIAL AND METHODS: We present the clinicopathological features of 3 new cases of POKC (2 women and 1 man; age range: 14-74 years). Immunohistochemical study included CK7, CK14, CK19 and Ki-67, and a systematic review of the literature was performed in PubMed, Scopus and Web of Science databases. RESULTS: All cases were located in the anterior gingiva (2 in maxilla and 1 mandible), and none corresponded to Gorlin-Goltz syndrome. High expression of CK14 was seen in all cases, with CK19 and CK7 been only focally positive. The expression of Ki-67 was located in the basal and parabasal cells in all cases. CONCLUSIONS: POKC is a rare gingival lesion that seems to originate from remnants of dental lamina or from the basal cells of the gingival epithelium and present a similar histopathology as compared to intraosseous OKC.

Gene polymorphisms in odontogenic keratocysts and ameloblastomas: A systematic review.

OBJECTIVES: The aim of this systematic review was to critically analyze available data on gene polymorphisms in odontogenic keratocysts (OKC) and ameloblastomas, including their possible relationship with clinical and histological features of these lesions. MATERIALS AND METHODS: A comprehensive search of Web of Science Scopus, PubMed, Cochrane Central Register of Controlled Trials and EMBASE was conducted using relevant key terms and supplemented by a gray literature search. Quality assessment of included studies was performed using criteria from the Strengthening the Reporting of Genetic Association (STREGA) statement. RESULTS: Ten studies were included in the final review. Survivin -31G/C, interleukin IL-1α -889 C/T, p53 codon 72 G/C, tumor necrosis factor TNF-α (-308G>A) and its receptor TNF-R1 (36A>G), glioma-associated oncogene homolog 1 rs2228224 and matrix metalloproteinase 2 rs243865 gene polymorphisms were reported to be associated with OKC. For ameloblastomas, p53 codon 72 G/C, X-ray repair cross-complementing protein 1-codons 194 and 399 and matrix metalloproteinase 9 rs3918242 gene polymorphisms were identified as risk factors. It was not possible to establish a relationship between specific polymorphisms and clinical and histological features of investigated lesions. CONCLUSIONS: Several gene polymorphisms might be considered as a risk factor for the development of these lesions. Future studies should investigate whether these polymorphisms might be used to identify patients with increased risk of recurrence or aggressive disease.

Dental Screening Including Panoramic Radiograph for Gorlin-Goltz Syndrome in Patients With Multiple Basal Cell Carcinomas.

PURPOSE: To answer the following clinical research question: "Among patients with multiple basal cell carcinomas (mBCCs), can panoramic radiograph (PaR) facilitate the diagnosis of Gorlin-Goltz syndrome (GGS)?" METHODS: This retrospective study enrolled mBCCs subjects who presented to a German tertiary care center between 1 January 2015 and 31 December 2021. The primary predictor was presence of syndromic mBCCs, and the main outcomes were jaw cysts and odontogenic keratocysts (OKCs). Descriptive, bi- and multivariate statistics, diagnostic test evaluation, and number needed to screen (NNS) were computed at α = 95%. RESULTS: The sample comprised 527 mBCCs patients (36.1% females; 6.8% GGS; 5.5% OKCs; mean age, 74.5 ± 15.8 years [range, 15-102]). There was a significant association between syndromic mBCCs and jaw cysts (P < .0001; NNS = 2 [95% CI, CI, 1.1 to 1.4]). In the adjusted logistic model, PaR identified GGS via radiographic diagnosis of jaw cysts in case of 1) age ≤ 35 years, 2) ≥ 5 BCCs, and 3) ≥ 1 high-risk BCCs. Nearly every jaw cyst identified by PaR was OKCs (P = .01; 95% CI, 3.1 to 3,101.4; NNS = 1.3 [95% CI, .9 to 2]). The post hoc power was 100%. CONCLUSIONS: Dental screening with the use of PaR for mBCCs patients, especially those aged ≤35 years, or with ≥5 BCCs, or ≥1 high-risk BCCs, may be helpful in detection and identification of GGS through recognition of OKCs.

Recurrent odontogenic keratocyst with orbital invasion.

Odontogenic keratocysts (OKCs) are aggressive lesions that have been variously classified as neoplasms or cysts according to the World Health Organisation (WHO). They can be challenging to surgically remove and the cysts can exhibit locally aggressive behaviour if incompletely excised. We describe a case of recurrent OKC invading the orbit requiring multidisciplinary approach for extended surgical excision, and review the current literature regarding this condition.

Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst.

OBJECTIVE: Odontogenic keratocyst (OKC) is a benign lesion that tends to recur after surgical treatment. In an attempt to clarify the molecular basis underlining the OKC pathobiology, we aimed to analyze its proteomic profile. MATERIALS AND METHODS: We compared the proteomic profiles of five OKC and matched normal oral mucosa by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we performed enrichment analysis and a literature search for the immunoexpression of the proteomics targets. RESULTS: We identified 1,150 proteins and 72 differently expressed proteins (log2 fold change ≥ 1.5; p < .05). Twenty-seven peptides were exclusively detected in the OKC samples. We found 35 enriched pathways related to cell differentiation and tissue architecture, including keratinocyte differentiation, keratinization, desmosome, and extracellular matrix (ECM) organization and degradation. The immunoexpression information of 11 out of 50 proteins identified in the enriched pathways was obtained. We found the downregulation of four desmosomal proteins (JUP, PKP1, PKP3, and PPL) and upregulation of ECM proteases (MMP-2, MMP-9, and cathepsins). CONCLUSIONS: Proteomic analysis strengthened the notion that OKC cells have a similar proteomic profile to oral keratinocytes. Contextual investigation of the differentially expressed proteins revealed the deregulation of desmosome proteins and ECM degradation as important alterations in OKC pathobiology.