Immunohistochemical Analysis of Dentigerous Cysts and Odontogenic Keratocysts Associated with Impacted Third Molars-A Systematic Review.

OBJECTIVE: This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars. MATERIALS AND METHODS: A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods. RESULTS: Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, p < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, p < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, p < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, p < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy. CONCLUSIONS: The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery.

Clinical and radiological documentation of complete remodeling of the mandibular bone after the enucleation of a large odontogenic keratocyst: 15 years follow-up of a unique case - A case report.

INTRODUCTION AND IMPORTANCE: Odontogenic keratocysts (OKC) are benign intraosseous cysts with expansive growth. They account for approximately 7.8 % of all jaw cysts and have a high recurrence rate. Herein, we present a minimally invasive approach for the surgical treatment of a remarkable variation of OKC with a 15-year radiological and clinical follow-up. PRESENTATION OF THE CASE: We present the case of a 42-year-old female patient with a large cyst in the mandible between teeth 35 and 45, who reported spontaneous swelling and paresthesia of the lower lip. Radiological imaging is crucial for treatment planning. The cyst was surgically treated with a single enucleation combined with adjuvant therapy to minimise recurrence. A titanium plate was inserted because of the size of the defect. Recurrence was observed one year later and treated with single enucleation and adjuvant therapy. After 15 years, complete healing, no signs of recurrence, and complete remodeling of the mandible were observed. CLINICAL DISCUSSION: The treatment of OKC remains the subject of varying approaches in the literature due to the lack of established general guidelines. One treatment option is single enucleation combined with adjuvant therapy to minimise recurrence, which can result in complete clinical and radiological remodeling of the bone. CONCLUSION: Direct enucleation combined with adjuvant therapy is a practical approach for treating large OKCs. It is associated with less morbidity and burden on the patient than enucleation with prior decompression or radical resection. Additionally, it shows no deficits in bone defect healing.

Immunohistochemical evaluation of Glut1 in dentigerous cysts, odontogenic keratocysts, and ameloblastoma.

Context: Glucose uptake may be considered the rate-limiting step for the growth and metabolism of the cancer cell. Studies on GLUT1 have shown that GLUT1 is involved in cell survival and proliferation in both healthy and pathological circumstances. GLUT1 expression is regarded as one of the crucial elements in the development of local aggressiveness, tumour invasiveness, and metastasis, particularly in malignant tumours. The role of glut1 in odontogenic cysts and tumours has remained uncertain. Aim: The aim of the study is to assess the expression of Glut1 in dentigerous cysts, odontogenic keratocysts, and ameloblastoma. Settings and Design: The study was conducted in GSL Dental College. The study design was a resprospective immunohistochemical study. Methods and Material: Formalin-fixed, paraffin-embedded blocks of histologically confirmed cases (n = 50), 10 cases of odontogenic keratocysts, dentigerous cysts, ameloblastomas solid, ameloblastomas unicystic, and dental follicles each. Brown colour staining was considered as positive staining for GLUT1. Quantitative analysis was performed by counting the number of labelled cells, and semi-quantitative analysis was conducted by assigning immunostaining intensity scores. Statistical Analysis: Chi-square test was used to compare differences between the groups. A P value of ≤0.05 was considered as statistically significant. Results: Odontogenic keratocysts and unicystic ameloblastoma showed ≥50% of label cells with strong intensity of staining. Odontogenic keratocysts and solid ameloblastoma showed sub-cellular localisation of staining in the cytoplasm and membrane. Dentigerous cysts exhibited combined nucleus, cytoplasm, and membrane sub-cellular localisation of staining. Conclusions: The development of ameloblastomas, odontogenic keratocysts, and dentigerous cysts appears to be influenced by GLUT-1. Variation in its expression may aid in explanation of some of the differences in biological activity of these lesions.

Beneficios de la descompresión y enucleación en lesiones quísticas de gran tamaño en la mandíbula / Benefits of decompression and enuclation in large cystic lesions in the jaw / Benefícios da descompressão e enuclação nas grandes lesões císticas na mandíbula

Las lesiones quísticas ocurren en los maxilares, por la presencia de células remanentes del neuroectodermo embrionario. La descompresión es una técnica conservadora para disminuir la presión intraquística mediante drenaje constante, permitiendo el crecimiento de nuevo hueso centrípeto de las paredes óseas del quiste. Objetivo: determinar los beneficios de la descompresión y enucleación en lesiones quísticas mandibulares, tomando como base la metodología de un caso clínico. Descripción del caso: se diagnosticó una lesión quística mandibular en paciente masculino de 27 años, que acudió a consulta mostrando secreción purulenta en mucosa trígono retromolar de UD 37, inicialmente asintomática. Se utilizaron como materiales la tomográfica computarizada de haz cónico, artefacto de drenaje autocurado, hemiarcada izquierda elaborada con Metil Metacrilato y aparato a base de cilindro. Como resultados se reveló imagen hipodensa de bordes definidos localizada en el límite posterior de cuerpo mandibular, borde anterior y parte de la rama ascendente mandibular del lado izquierdo; extendida en sentido cefálico caudal desde la cresta alveolar y borde anterior de la rama hasta la cortical superior del conducto mandibular. Conclusión: Se confirmó diagnóstico de quiste periapical, quiste residual y ameloblastoma. Se realizó biopsia incisional de la lesión para estudio histopatológico y la descompresión con dispositivo personalizado a enucleación conminada con solución de Carnoy, resultando el tratamiento conservador efectivo complementado por la enucleación de una membrana quística más gruesa y menos friable.

Cystic lesions occur in the jaws due to the presence of remnant cells of the embryonic neuroectoderm. Decompression is a conservative technique to decrease intracystic pressure by constant drainage, allowing the growth of new centripetal bone from the bony walls of the cyst. Objective: to determine the benefits of decompression and enucleation in mandibular cystic lesions, based on the methodology of a clinical case. Case description: a cystic mandibular lesion was diagnosed in a 27 year old male patient, who came for consultation showing purulent secretion in the trigone retromolar mucosa of UD 37, initially asymptomatic. The materials used were cone beam computed tomography, self-curing drainage device, left hemiarch made with Methyl Methacrylate and cylinder based apparatus. The results revealed a hypodense image with defined borders located in the posterior limit of the mandibular body, anterior border and part of the ascending mandibular branch on the left side; extended in a caudal cephalic direction from the alveolar crest and anterior border of the branch to the superior cortical of the mandibular duct. Conclusion: Diagnosis of periapical cyst, residual cyst and ameloblastoma was confirmed. An incisional biopsy of the lesion was performed for histopathological study and decompression with a customized device to enucleation with Carnoy's solution, resulting in effective conservative treatment complemented by enucleation of a thicker and less friable cystic membrane.

As lesões císticas ocorrem nos maxilares, devido à presença de células remanescentes da neuroectoderme embrionária. A descompressão é uma técnica conservadora que visa reduzir a pressão intracística por meio de drenagem constante, permitindo o crescimento de novo osso centrípeto a partir das paredes ósseas do cisto. Objetivo: determinar os benefícios da descompressão e da enucleação em lesões císticas mandibulares, com base na metodologia de um caso clínico. Descrição do caso: foi diagnosticada uma lesão cística mandibular em um paciente do sexo masculino, 27 anos, que se apresentou para consulta apresentando secreção purulenta na mucosa do trígono retromolar do UD 37, inicialmente assintomática. Os materiais utilizados foram tomografia computadorizada de feixe cônico, dispositivo de drenagem autopolimerizável, hemiarco esquerdo confeccionado com metacrilato de metila e aparelho de base cilíndrica. Os resultados revelaram uma imagem hipodensa com limites definidos localizada no limite posterior do corpo mandibular, bordo anterior e parte do ramo mandibular ascendente do lado esquerdo; estendendo-se em direção cefálica caudal desde a crista alveolar e bordo anterior do ramo até ao córtex superior do ducto mandibular. Conclusão: Foi confirmado o diagnóstico de quisto periapical, quisto residual e ameloblastoma. Foi efectuada uma biopsia incisional da lesão para estudo histopatológico e descompressão com um dispositivo adaptado à enucleação cominutiva da solução de Carnoy, resultando num tratamento conservador eficaz complementado pela enucleação de uma membrana quística mais espessa e menos friável.

Discovery of metabolite biomarkers for odontogenic keratocysts.

INTRODUCTION: Odontogenic keratocysts (OKCs) are locally aggressive and have a high rate of recurrence, but the pathogenesis of OKCs is not fully understood. We aimed to investigate the serum metabolomic profile of OKCs and discover potential biomarkers. METHODS: Metabolomic analysis was performed on 42 serum samples from 22 OKC patients and 20 healthy controls (HCs) using gas chromatography‒mass spectrometry to identify dysregulated metabolites in the OKC samples. LASSO regression and receiver operating characteristic (ROC) curve analyses were used to select and validate metabolic biomarkers and develop diagnostic models. RESULTS: A total of 73 metabolites were identified in the serum samples, and 24 metabolites were dysregulated in the OKC samples, of which 4 were upregulated. Finally, a diagnostic panel of 10 metabolites was constructed that accurately diagnosed OKCs (sensitivity of 100%, specificity of 100%, area under the curve of 1.00). CONCLUSION: This study is the first to investigate the metabolic characteristics and potential metabolic biomarkers in the serum of OKC patients using GC‒MS. Our study provides further evidence to explore the pathogenesis of OKC.

A case of odontogenic keratocyst in the buccal space: characterization by multimodality imaging including computed tomography, diffusion-weighted magnetic resonance imaging, and ultrasonography.

Odontogenic keratocyst (OKC) is a relatively common non-inflammatory jaw lesion. OKC is known to occur most often in the mandibular angle and mandibular ramus, but rarely outside the bone. In this report, we describe characteristic multimodality imaging of OKC in the buccal space, especially diffusion-weighted MR imaging (DWI) with apparent diffusion coefficient (ADC) mapping, extra-oral and intra-oral ultrasonography. On clinical examination, an approximately 20 mm in diameter mass with elastic hardness was found the left side of the buccal area. Contrast-enhanced CT showed areas of internal non-contrast lesions in the left buccal space. On T1-weighted image, the mass showed multilocular high signal intensity, and homogeneous internal. T2-weighted images revealed high signal at the marginal part and slightly median signal in the internal part. STIR images revealed a heterogeneous high signal in the interior. Furthermore, DWI and ADC map showed high signal and moderate-to-low signal intensity, respectively. ADC value of the lesion was 1.55 × 10-3 mm2 s-1. On extra-oral ultrasonography, the tumor showed clear boundary, hypoechoic, homogeneous internal architecture and vascular signals, and heterogeneous hard of the lesion. On intra-oral ultrasonography also showed clear boundary, hypoechoic, homogeneous internal architecture, heterogeneous hard of the tumor, and back echo enhance. The histopathologic diagnosis based on a full excisional specimen was odontogenic keratocyst. This case suggests that multimodality imaging, especially MR imaging with ADC and DWI, and extra and intra-oral ultrasonography with color Doppler imaging and elastography, could be effective for evaluating buccal lesions.

Radiological evaluation of odontogenic keratocysts in patients with nevoid basal cell carcinoma syndrome: A review.

Background: Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal dominant syndrome that has various expressions in each patient. Generally; NBCCS is followed by multiple nevoid basal cell carcinoma of the skin, orbital anomalies, skeletal anomalies, central nervous system anomalies and multiple odontogenic keratocysts (OK). NBCCS is usually diagnosed between the ages of 5-30 years, with multiple basal cell carcinomas of the skin and OKs in the jaws as the initial findings. The purpose of this paper is to describe and compare the radiographic findings of the OKs in NBCCS patients in the literature with additional cases. Materials and Methods: In this study, we evaluated the OKs of the patients with NBCCS in PubMed Database with 5 additional cases from our database. A total of 305 articles were found and the articles in English with full-text access were evaluated. Results: Despite all limitations for a fair discussion; we would like to state that among 59 cases that specified whether a 3D or 2D imaging modality was used, 29 cases were only interpreted with 2D data which should be avoided in OK evaluation. Discussion: According to the World Health Organization's Classification of Head and Neck Tumours Book which was published in 2017, OKs in NBCCS has a higher chance to have small satellite cystic lesions which increase their recurrence possibility post-operatively, thus, a thorough clinical and 3D radiographic evaluation should be performed both to NBCCS patients and non-syndromic OK patients to avoid any recurrence. Conclusion: High recurrence rates of OKs should be reminded all the time. Radiographic examinations with 3D imaging modalities should be done in patients with NBCCS in order to provide a concise diagnosis and optimum treatment.

Comparative immunohistochemical analysis of WT-1, Syndecan and Snail in Ameloblastoma and odontogenic keratocyst: A retrospective study.

Background: The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm's Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma and odontogenic keratocyst (OKC) and to analyse their potential role in pathogenesis. Methods and Material: Immunohistochemical analysis was performed to evaluate WT-1, Syndecan and Snail expression in Ameloblastoma (n = 20) and OKC (n = 20). Topographical immunoexpression pattern of Ameloblast-like cells, Stellate Reticulum-like cells in Ameloblastoma and basal layer as well as suprabasal layer of cells of OKC were also compared. The results obtained were subjected to ANOVA test and Tukey HSD test through SPSS software 20.0 for Microsoft Windows. Results: WT-1 and Snail overexpression was seen in both Ameloblastoma and OKCs. Syndecan, responsible for maintaining normal cellular morphology, cell-cell adhesion and differentiation was significantly downregulated in both the lesions. The Ameloblasts-like cells and the basal cells showed significantly higher immunopositivity for WT-1 and Syndecan as compared to that of basal cells. An inverse relation was noted for Snail protein. The ANOVA test predicted a statistically significant difference of expression across the lesions with a P value <0.0001 for Syndecan and Snail. Conclusions: The under-expression of epithelial membrane protein Syndecan-1 and upregulation of EMT transcription factor Snail can promote local invasion and is indicative of poor prognosis of these lesions. The overexpression of WT-1 results in tumorigenesis, proliferation and localized aggressiveness of Ameloblastoma and intrabony growth of OKC. Further investigation on the biologic behaviour of OKC is still recommended to arrive at more specific conclusions regarding its nature.

Significance of EGFR investigation in odontogenic keratocyst: a narrative review.

BACKGROUND: The recent classification of odontogenic keratocysts (OKSs) recognized them as benign neoplasms, although previous findings have revealed their aggressive nature. Immunohistochemical and molecular analyses have investigated OKSs, but the role of epidermal growth factor receptor (EGFR) has not been fully investigated, despite the importance of this oncogene in the process of carcinogenesis in tumors of epithelial origin. The EGFR protein is usually overexpressed, and the EGFR gene is mutated or amplified. AIMS OF STUDY: This brief review aims to emphasize the importance of EGFR detection in these types of cysts. METHODS AND RESULTS: It was revealed that the majority of the studies examined EGFR protein expression using immunohistochemical methods; however, considering EGFR gene variants, mutations were less explored in the previous period from 1992 to 2023. Although EGFR gene polymorphisms are clinically important, they were not identified in the present study. CONCLUSIONS: In light of the current significance of EGFR variants, it would be beneficial to examine them in odontogenic lesions. This would enable resolving of discrepancies about their nature, and potentially enhance classifications OKCs in the future.

Volumetric changes in the size of odontogenic keratocysts after decompression followed by enucleation, peripheral ostectomy, and Carnoy's solution: A retrospective study.

The study aimed to retrospectively analyze the reduction pattern of odontogenic keratocysts (OKCs) after decompression, followed by enucleation (EN), peripheral ostectomy (PO), and Carnoy's solution (CS) to establish the appropriate time for inserting implants, along with assessing the long-term success of conservative treatment with adjunctive therapy. The predictable variables were the reduction pattern and the study's treatment option. The outcome variable was the volumetric changes in the size of bony defects. These changes were determined using a percentage difference and a reduction rate. They were recorded after decompression and one, three, six, twelve, and eighteen months after EN. P-values of .05 were considered significant. The study included 66 patients with 71 OKCs. Males, younger ages, and mandibular OKCs significantly predominated. The decompression significantly changed the initial volume from 135.40 ± 1.2 cm3 to 101.55 ± 0.1 cm3 with 28.6 percentage difference and 25% reduction rate. At the end of the first and third months after EN, the reduction pattern is 50.0%-75.5% of the initial volume, with no significant prediction for the direction of the reduction pattern. After 18 months, all bony defects disappeared, with no recurrences for the next 18 years. In conclusion, the reduction pattern is 75.5% of its initial volume at the end of the third month after OKC management. Therefore, within the limitations of the study, its treatment approach seems to be an option amongst other protocols that includes a view to early implant based dental rehabilitation.

Comparative Molecular Genetics of Odontogenic Keratocysts in Sporadic and Syndromic Patients.

Odontogenic keratocysts (OKCs) are common cysts of odontogenic origin that usually occur as a single nonsyndromic cyst in isolation (sporadic) or as syndromic multiple cysts as a manifestation of naevoid basal cell carcinoma syndrome. Alterations involving the PTCH gene are the most commonly identified factor associated with up to 85% and 84% of naevoid basal cell carcinoma syndrome and sporadic cases, respectively. Other Hedgehog pathway and non-Hedgehog pathway-associated genes have been implicated in the pathogenesis of OKCs. This pilot study used the Affymetrix OncoScan molecular assay to perform a comparative genomic analysis between 4 sporadic and 3 syndromic cases of OKC to identify molecular drivers that may be common and/or distinct in these 2 groups. The majority of alterations detected in both groups were copy number neutral loss of heterozygosity. Despite distinct molecular signatures observed in both groups, copy number neutral loss of heterozygosity alterations involving chromosome 9q affecting not only PTCH but also the NOTCH1 gene were detected in all syndromic and 3 sporadic cases. Loss of heterozygosity alterations involving 16p11.2 affecting genes not previously described in OKCs were also detected in all syndromic and 3 sporadic cases. Furthermore, alterations on 22q11.23 and 10q22.1 were also detected in both groups. Of note, alterations on 1p13.3, 2q22.1, and 6p21.33 detected in sporadic cases were absent in all syndromic cases. This study demonstrates that a more common group of genes may be affected in both groups of OKCs, whereas other alterations may be useful in distinguishing sporadic from syndromic cysts. These findings should be validated in larger OKC cohorts to improve molecular diagnosis and subsequent patient management.

The Prevalence of EBV and KSHV in Odontogenic Lesions.

OBJECTIVES: Odontogenic lesions evolve as a result of altered dental development. This study aimed to evaluate the prevalence and the coinfection of Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) in radicular cysts, dentigerous cysts, odontogenic keratocysts, and ameloblastomas. METHODS: Polymerase chain reaction (PCR) was used to analyse 66 cases of odontogenic lesions for the presence of EBV-DNA and KSHV-DNA. These lesions were 15 radicular cysts, 16 dentigerous cysts, 18 odontogenic keratocysts, and 17 ameloblastomas. RESULTS: EBV-DNA was detected in 24 (36.4%) of the studied samples as follows: 6 samples (40.0%) of radicular cysts, 4 (25.0%) of dentigerous cysts, 10 (55.6 %) of odontogenic keratocysts, and 4 (23.5%) of ameloblastomas (P = .168). KSHV-DNA was found in 16 (24.2%) of the studied samples as follows: 1 sample (6.7%) of radicular cysts, 6 (37.5%) of dentigerous cysts, 8 (44.4 %) of odontogenic keratocysts, and 1 (5.9%) of ameloblastomas (P = .001). Additionally, EBV and KSHV were positively correlated in all studied samples (P = .002). CONCLUSIONS: Both EBV and KSHV are found in odontogenic cysts and ameloblastomas. KSHV and EBV are more prevalent in odontogenic keratocysts than in other studied odontogenic lesions. Further, there is a high prevalence of EBV and KSHV coinfection in odontogenic cysts and ameloblastomas.

Prognostic relevance of clinicopathological factors in sporadic and syndromic odontogenic keratocysts: A comparative study.

BACKGROUND: Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs. OBJECTIVES: This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC. MATERIAL AND METHODS: We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence. RESULTS: We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio. CONCLUSIONS: The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.

Odontogenic Keratocyst with Diverse Variations: A Rare Case Report.

Rationale: An odontogenic keratocyst (OKC) is a developmental odontogenic cyst lined by squamous epithelium having intrinsic growth potential. Hence, metaplastic changes such as the formation of mucous cells, ciliated cells, and hyaline bodies with ortho/para keratinisation have been known to create unusual histopathological variations. Patient Concerns: A 34-year-old male patient reported with swelling on the lower right side of the face and numbness on the overlying skin. Diagnosis: Based upon the histopathological findings, a final diagnosis of glandular odontogenic cyst with OKC was confirmed presenting mixed features of basal layer palisading squamous epithelium with goblet cells and satellite cysts appeared to be entrapped in the connective tissue wall. Treatment: Surgical enucleation of the cyst was done. Outcomes: No recurrence was reported in 1 year of follow-up. Take-away Lessons: Diverse variations appear within odontogenic cysts and tumours. The high recurrence rate and aggressive nature of the cyst, divulges appropriate treatment and long-term follow-up.

Ensemble Deep-Learning-Based Prognostic and Prediction for Recurrence of Sporadic Odontogenic Keratocysts on Hematoxylin and Eosin Stained Pathological Images of Incisional Biopsies.

(1) Background: Odontogenic keratocysts (OKCs) are enigmatic developmental cysts that deserve special attention due to their heterogeneous appearance in histopathological characteristics and high recurrence rate. Despite several nomenclatures for classification, clinicians still confront challenges in its diagnosis and predicting its recurrence. This paper proposes an ensemble deep-learning-based prognostic and prediction algorithm, for the recurrence of sporadic odontogenic keratocysts, on hematoxylin and eosin stained pathological images of incisional biopsies before treatment. (2) Materials and Methods: In this study, we applied a deep-learning algorithm to an ensemble approach integrated with DenseNet-121, Inception-V3, and Inception-Resnet-V3 classifiers. Around 1660 hematoxylin and eosin stained pathologically annotated digital images of OKC-diagnosed (60) patients were supplied to train and predict recurrent OKCs. (3) Results: The presence of SEH (p = 0.004), an incomplete epithelial lining, (p = 0.023), and a corrugated surface (p = 0.049) were the most significant histological parameters distinguishing recurrent and non-recurrent OKCs. Amongst the classifiers, DenseNet-121 showed 93% accuracy in predicting recurrent OKCs. Furthermore, integrating and training the traditional ensemble model showed an accuracy of 95% and an AUC of 0.9872, with an execution time of 192.9 s. In comparison, our proposed model showed 97% accuracy with an execution time of 154.6 s. (4) Conclusions: Considering the outcome of our novel ensemble model, based on accuracy and execution time, the presented design could be embedded into a computer-aided design system for automation of risk stratification of odontogenic keratocysts.

Multidisciplinary approach to Gorlin-Goltz syndrome: from diagnosis to surgical treatment of jawbones.

BACKGROUND: Gorlin syndrome, also known as Gorlin-Goltz syndrome (GGS) or basal cell nevus syndrome (BCNS) or nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant familial cancer syndrome. It is characterized by the presence of numerous basal cell carcinomas (BCCs), along with skeletal, ophthalmic, and neurological abnormalities. It is essential to anticipate the diagnosis by identifying the pathology through the available diagnostic tests, clinical signs, and radiological manifestations, setting up an adequate treatment plan. MAIN BODY: In the first part, we searched recent databases including MEDLINE (PubMed), Embase, and the Cochrane Library by analyzing the etiopathogenesis of the disease, identifying the genetic alterations underlying them. Subsequently, we defined what are, to date, the major and minor clinical diagnostic criteria, the possible genetic tests to be performed, and the pathologies with which to perform differential diagnosis. The radiological investigations were reviewed based on the most recent literature, and in the second part, we performed a review regarding the existing jawbone protocols, treating simple enucleation, enucleation with bone curettage in association or not with topical use of cytotoxic chemicals, and "en bloc" resection followed by possible bone reconstruction, marsupialization, decompression, and cryotherapy. CONCLUSION: To promote the most efficient and accurate management of GGS, this article summarizes the clinical features of the disease, pathogenesis, diagnostic criteria, differential diagnosis, and surgical protocols. To arrive at an early diagnosis of the syndrome, it would be advisable to perform radiographic and clinical examinations from the young age of the patient. The management of the patient with GGS requires a multidisciplinary approach ensuring an adequate quality of life and effective treatment of symptoms.

Gorlin-Goltz syndrome with familial manifestation.

AIMS: The detection of odontogenic keratocysts (OKC) in the oral cavity is one of the main criteria for the clinical manifestation of Gorlin-Goltz syndrome (Nevoid Basal Cell Carcinoma Syndrome - NBCCS). From a clinical point of view, we distinguish between "syndromic" and "sporadic" OKC. Syndromic cysts, often multifocal, may be an accidental finding on X-ray examination. They can manifest gradually depending on the development of permanent dentition. Sporadic cysts are rather solitary lesions with clinical manifestation in adulthood. METHODS: Mutations in the PTCH1 gene are thought to be the cause of the clinical manifestation of NBCCS. These abnormalities can be transmitted from one generation to another and lead to a familial occurrence of the disease. In 35-50% of cases, these are a newly arising mutations. It is necessary to take into account the typical manifestations which in the next generation begin at a younger age and the disease usually has a more serious course. RESULTS: We found a familial manifestation of NBCCS in two pairs of patients (mother and daughter and two siblings). Odontogenic keratocysts and cutaneous basal cell carcinomas were diagnosed and genetic testing revealed mutations in the PTCH 1 gene in all four individuals. CONCLUSIONS: With regard to the possibility of familial occurrence of NBCCS, it is necessary to pay increased attention to family history and, if necessary, to ensure clinical and genetic examination of parents and other family members. Patients of childbearing potential with evidence of NBCCS should be informed of the increased likelihood of the disease in the offspring.

Epithelial-mesenchymal markers and their correlation with clinical aspects in odontogenic keratocysts / Marcadores epitélio-mesênquima e sua correlação com aspectos clínicos em lesões de ceratocisto odontogênico

ABSTRACT Objective: Odontogenic keratocysts have a high recurrence rate and aggressive clinical behavior. The event called epithelial-mesenchymal transition is a process in which the epithelial cell loses its epithelial characteristics and acquires properties typical of mesenchymal cells. Studies have already demonstrated that odontogenic keratocysts has expression of tumor markers, but the lack of clarification about its development mechanism and molecular composition makes the therapeutic options remain limited. The aim of this study is to evaluate the expression of epithelial-mesenchymal transition marker proteins in these lesions, correlating the expression of these proteins with clinical aspects of each case. Methods: Patients with odontogenic keratocysts diagnoses, treated by the Department of Oral and Maxillofacial Surgery of the Erasto Gaertner Hospital, Curitiba, Brazil in the period between 2016 and 2019 were evaluated by immunohistochemical analysis, to assess the expression of epithelial-mesenchymal transition markers (Vimentin, beta-catenin and E-cadherin) by qualitative analysis. Results: Eighteen patients were included, with a mean age of 43 years, and most of them were male. The mandible was more affected than the maxilla. No association between the clinical characteristics of the cysts and the immunohistochemical profile for epithelial-mesenchymal transition proteins was observed. Conclusion: The positivity of E-cadherin and negativity of vimentin demonstrates that its function is preserved. Loss of function of E-cadherin is associated with worse prognosis. The identification of the epithelial-mesenchymal transition process as a prognostic marker for odontogenic cysts and tumors could be an important tool for defining treatment.

RESUMO Objetivo: O ceratocisto odontogênico têm uma alta taxa de recorrência e comportamento clínico agressivo. O evento chamado transição epitelial-mesênquima (TEM) é um processo no qual a célula epitelial perde suas características epiteliais e adquire propriedades típicas das células mesenquimais. Estudos já demonstraram que o ceratocisto odontogênico tem expressão de marcadores tumorais, mas a falta de esclarecimento sobre seu mecanismo de desenvolvimento e composição molecular faz com que as opções terapêuticas permaneçam limitadas. O objetivo deste estudo é avaliar a expressão das proteínas marcadoras de transição epitelial-mesênquima nestas lesões, correlacionando a expressão destas proteínas com os aspectos clínicos de cada caso. Métodos: Os pacientes com diagnóstico de ceratocisto odontogênico, tratados pelo Serviço de Cirurgia Bucomaxilofacial do Hospital Erasto Gaertner, Curitiba, Brasil, no período entre 2016 e 2019, foram avaliados por análise imunohistoquímica, para avaliar a expressão dos marcadores transição epitelial-mesênquima (Vimentina, beta-catenina e E-cadherina). Resultados: Foram incluídos 18 pacientes, com idade média de 43 anos, e a maioria deles eram do sexo masculino. A mandíbula foi mais afetada do que a maxila. Não foi observada associação entre as características clínicas dos cistos e o perfil imuno-histoquímico das proteínas transição epitelial-mesênquima. Conclusão: A positividade da E-caderina e a negatividade da vimentina demonstram que a sua função está preservada. A perda da função da E-caderina está associada a um pior prognóstico. Identificar o processo da transição epitelial-mesênquima como um marcador de prognóstico para cistos e tumores odontogênicos pode ser uma ferramenta importante para definir o tratamento dessas lesões.

Deep Learning-Based Microscopic Diagnosis of Odontogenic Keratocysts and Non-Keratocysts in Haematoxylin and Eosin-Stained Incisional Biopsies.

BACKGROUND: The goal of the study was to create a histopathology image classification automation system that could identify odontogenic keratocysts in hematoxylin and eosin-stained jaw cyst sections. METHODS: From 54 odontogenic keratocysts, 23 dentigerous cysts, and 20 radicular cysts, about 2657 microscopic pictures with 400× magnification were obtained. The images were annotated by a pathologist and categorized into epithelium, cystic lumen, and stroma of keratocysts and non-keratocysts. Preprocessing was performed in two steps; the first is data augmentation, as the Deep Learning techniques (DLT) improve their performance with increased data size. Secondly, the epithelial region was selected as the region of interest. RESULTS: Four experiments were conducted using the DLT. In the first, a pre-trained VGG16 was employed to classify after-image augmentation. In the second, DenseNet-169 was implemented for image classification on the augmented images. In the third, DenseNet-169 was trained on the two-step preprocessed images. In the last experiment, two and three results were averaged to obtain an accuracy of 93% on OKC and non-OKC images. CONCLUSIONS: The proposed algorithm may fit into the automation system of OKC and non-OKC diagnosis. Utmost care was taken in the manual process of image acquisition (minimum 28-30 images/slide at 40× magnification covering the entire stretch of epithelium and stromal component). Further, there is scope to improve the accuracy rate and make it human bias free by using a whole slide imaging scanner for image acquisition from slides.

Imaging of Gorlin-Goltz syndrome: Series of 2 cases.

Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder with multisystemic involvement. It is characterized by the triad of multiple baso-cellular epitheliomas, odontogenic keratocysts (OKC) in the jaws and skeletal anomalies. Later, it was found that calcification of falx is also highly specific. We present radiological findings in case series of two cases, one with multiple OKC, calcified falx, skin lesions, and fibrous dysplasia of sphenoid and second with multiple OKC, calcified falx, vertebral anomaly and medulloblastoma.