MMP13 Expression and Activity Suggest Its Role in Bone Resorption in Ameloblastomas.

BACKGROUND: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. METHODS: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. RESULTS: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor-bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. CONCLUSION: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression.

Targeted therapies in ameloblastomas and amelobastic carcinoma-A systematic review.

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.

Adenoid ameloblastoma revisited: A discursive exploration of its histological dualism, molecular aberrations, and clinical recurrence.

Adenoid ameloblastoma (AA) is a rare benign but locally aggressive odontogenic tumor originating from the remnants of the dental lamina or enamel organ. It was newly incorporated into the 2022 WHO classification of odontogenic lesions, standing as the sole novel entity in this update. AA is also regarded as a hybrid tumor because of the combination of histological characteristics observed in both adenomatoid odontogenic tumors and ameloblastoma. Clinically, it presents similarly to other ameloblastoma variants, with patients typically exhibiting a painless, slow-growing jaw swelling. However, this subtype is noted for its more aggressive behavior, including a higher recurrence rate and greater local invasiveness. Histopathologically, AA is distinguished by an intricate arrangement of epithelial islands, cords, and strands, generating a cribriform architectural pattern, with peripheral palisading and central stellate reticulum-like formations. Immunohistochemical profiling reveals the expression of epithelial differentiation markers, including cytokeratins, and proliferative markers such as Ki-67, further corroborating its aggressive phenotype. While its precise etiopathogenesis remains obscure, the unique histological characteristics imply a potentially distinct underlying molecular pathway. Due to its aggressive nature, AA necessitates meticulous clinical and histopathological evaluation and tailored therapeutic strategies to mitigate recurrence risks and optimize patient prognoses. Furthermore, this review integrates histological and molecular insights from recent studies conducted after its inclusion in the updated WHO classification.

Exceptional Evolution of a Squamous Odontogenic Tumor in the Jaw: Molecular Approach.

A squamous odontogenic tumor (SOT) is an epithelial locally benign neoplasia derived from the periodontium of the jaws. It is considered a lesion of low incidence. Predominantly, it affects the mandible, although both jaw bones may be involved. Here, we discuss the malignant clinical evolution of an SOT lesion in an 80-year-old female patient. The patient exhibited an expansive triangular lesion at the inferior right quadrant. Surgery was performed and an SOT was diagnosed (2019). Two years after, the lesion grew, and the analysis of the biopsy revealed SOT malignization with pleomorphic atypical squamous cells, characteristics of a squamous cell carcinoma (2021). Massive DNA sequencing of formalin-fixed-paraffin-embedded specimens of the initial and relapsed tumors indicated pathogenic mutations in RET and POLE genes in both tumors, loss of ALK, and gain of CDKN1B and MAP2K in the relapse. In addition, the clinical, radiographic, and microscopic features of this neoplasm are discussed and compared with those already published. The case presented contributes to the better understanding of this SOT tumor entity and to indicates its malignant evolution, together with its biological behavior and its histologic, clinical, and radiographic features. Also, it aims to stress the importance of deeper genetic analyses in rare diseases to uncover mutations that help to select a personalized treatment.

Curettage combined with decompression for the treatment of ameloblastoma in children: report of two cases.

BACKGROUND: Ameloblastoma (AM) is the most common benign odontogenic tumor, which is more often detected in the mandible than maxilla, especially the mandibular body and mandibular angle. Pediatric AM is a rare disease, especially in patients aged 10 and younger. Compared with the mainstream osteotomy and reconstructive surgery for adult ameloblastoma, there is more room for discussion in the treatment of pediatric ameloblastoma. The postoperative functional and psychological influence can not be ignored. Especially for children in the period of growth and development, an osteotomy is often challenging to be accepted by their parents. We report two patients with ameloblastoma under 10 years old who are treated with curettage and fenestration, which is a beneficial method for children with ameloblastoma. CASE PRESENTATION: We present two cases of classic ameloblastoma in children. We describe in detail the patients' characteristics, treatment processes, and follow-up result. The bone formation and reconstruction in the lesion area after fenestration decompression and curettage are recorded at every clinic review. The surgical details and principles of curettage and decompression are also described and discussed. The two patients have good bone shape recovery and no recurrence. CONCLUSIONS: Children are in the growth and development period and possess an extremely strong ability of bone formation and reconstruction. Based on the principles of minimally invasive and functional preservation, we believe that curettage combined with decompression can be the first choice for treating AM in children, especially for mandibular lesions.

Ameloblastic fibrosarcoma of the maxilla arising in an old woman, a rare case report and literature review.

BACKGROUND: Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor, commonly occurring in young adults and typically affecting the mandibular region. We report an exceptionally rare and highly atypical case of AFS in an elderly female patient originating from the maxillary bone. CASE PRESENTATION: A 66-year-old woman was admitted with a two-week history of a lump in her left upper molar. CT scans suggested a cyst in the maxillary bone. An incisional biopsy revealed a spindle cell neoplasm. MRI showed abnormalities in the left maxilla, indicating a possible tumorous lesion. The patient underwent a subtotal maxillectomy, wide tumor excision, intraoral epithelial flap transplantation, and dental extraction. Histology identified atypical tumor cells with visible mitotic figures. Immunohistochemistry showed negative for PCK and CD34 expression, but positive for Vimentin and SMA expression. The Ki-67 proliferation index ranged from 30 to 50%. These findings suggested a potentially malignant soft tissue tumor in the left maxilla, leaning towards a diagnosis of AFS. The patient received postoperative radiotherapy. There was no recurrence during the six-month follow-up. CONCLUSION: Based on repeated pathological evidence, we report a rare case of an elderly female with AFS originating from the maxillary bone. Surgery and postoperative radiotherapy resulted in a favorable outcome.

Odontogenic carcinoma with dentinoid: case report and literature review of a rare entity.

BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. CASE PRESENTATION: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and ß-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

[Three-dimensional radiographic features of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor].

OBJECTIVE: To analyze the three-dimensional radiographic characteristics of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor using spiral computed tomography (CT) and cone-beam computed tomography (CBCT). METHODS: Clinical records, histopathological reports, and CBCT or non-enhanced spiral CT images of 19 consecutive patients with calcifying odontogenic cyst (COC) and 16 consecutive patients with calcifying epithelial odontogenic tumor (CEOT) were retrospectively acquired, and radiographic features, including location, size, expansion, internal structure and calcification, were analyzed. RESULTS: Among the 19 COC cases (12 males and 7 females, with an average age of 27 years), 89.5% (17/19) of the lesions originated from the anterior and premolar areas, 100.0% of them exhibited cortex expansion, and 78.9% had discontinued cortex. Among the 16 CEOT cases (3 males and 13 females, with an average age of 36 years), 81.3% (13/16) of the lesions were in the premolar and molar areas, 56.3% of them exhibited cortex expansion, and 96.8% had discontinued cortex. According to the distribution of internal calcifications, these lesions were divided into: Ⅰ (non-calcification type): absence of calcification; Ⅱ (eccentric marginal type): multiple calcifications scattered along one side of the lesion; Ⅲ (diffused type): numerous calcifications diffusely distributed into the lesion; Ⅳ (plaque type): with a ≥ 5 mm calcified patch; Ⅴ (peri-coronal type): multiple calcifications clustered around impacted teeth. Calcifications were present in 73.7% of COC lesions, including 9 type Ⅱ, 3 type Ⅲ and 2 type Ⅳ lesions, and 42.8% of CEOT lesions had calcification images, including 2 type Ⅲ and 5 type Ⅴ lesions. Six COC lesions had odontoma-like images. Moreover, 8 of 9 type Ⅰ CEOTs were histologically Langerhans cell-rich subtype, which had a smaller size (with an average mesiodistal diameter of 17.8 mm) and were not associated with impacted teeth. CONCLUSION: COC lesions tended to originate from the anterior part of the jaw and exhibit cortex expansion, and were sometimes associated with odontoma. CEOT commonly occurred in the posterior jaw and had discontinued cortex. Two lesions had significantly different calcification map. Over 70% of COC lesions had calcification images, which were mostly scattered along one side of the cysts, far from the impacted teeth. Approximately 60% of CEOT lesions exhibited smaller size and non-calcification, and the remaining CEOT cases often had calcification images clustered around the impacted teeth.

Spontaneous mandibular follicular ameloblastoma in a female Sprague-Dawley rat.

Ameloblastoma is a locally aggressive tumor derived from the odontogenic epithelium of the developing tooth germ. It is rarely reported in experimental Sprague-Dawley (SD) rats. In this 90-day percutaneous repeated-dose toxicity study, mandibular nodules were observed from day 56 to 90. Upon necropsy, a well-demarcated nodule, approximately 1.2×1.0×1.0 cm, was found attached to the mandibular bone, alongside the unerupted left incisor. Histopathologically, the epithelial cells formed islands, nests, or anastomosing strands. The epithelial islands were surrounded by a peripheral layer of tall columnar cells with antibasilar nuclei arranged in a palisading pattern. Several mitotic cells were observed. Some epithelial islands displayed cystic degenerative changes and squamous metaplasia. Necrotic tissue with inflammatory cell infiltration was observed at the tumor margins. Immunohistochemically, the neoplastic epithelial islands and mesenchymal components exhibited positivity for pan-cytokeratin and vimentin, respectively. Based on these features, the case was diagnosed as follicular ameloblastoma in an SD rat.

IL-6 Plays a Critical Role in Stromal Fibroblast RANKL Induction and Consequent Osteoclastogenesis in Ameloblastoma Progression.

Ameloblastoma (AB) is the most common benign, epithelial odontogenic tumor that occurs in the jawbone. AB is a slow-growing, benign epithelial tumor but shows locally invasive growth, with bone resorption or recurrence if not adequately resected. From these points of view, understanding the mechanism of AB-induced bone resorption is necessary for better clinical therapy and improving patients' quality of life. In bone resorption, osteoclasts play critical roles, and RANKL is a pivotal regulator of osteoclastogenesis. However, the source of RANKL-expressing cells in the AB tumor microenvironment is controversial, and the mechanism of osteoclastogenesis in AB progression is not fully understood. In this study, we investigated the distribution of the RNA expression of RANKL in AB specimens. We found that PDGFRα- and S100A4-positive stromal fibroblasts expressed RANKL in the AB tumor microenvironment. Moreover, we analyzed the mechanisms of osteoclastogenesis in the AB tumor microenvironment using the human AB cell line AM-1 and a human primary periodontal ligament fibroblast cells. The results of histopathologic and in vitro studies clarified that the interaction between AB cells and stromal fibroblasts upregulated IL-6 expression and that AB cells induced RANKL expression in stromal fibroblasts and consequent osteoclastogenesis in AB progression.

Interrogation of TERT promoter hotspot mutations in ameloblastoma and ameloblastic carcinoma.

BACKGROUND: TERT promoter mutations increase telomerase activity, conferring cell immortality. The coexistence of TERT promoter mutations with BRAFV600E is associated with aggressiveness. Ameloblastoma and ameloblastic carcinoma are infiltrative neoplasms that harbor BRAFV600E; however, it remains unknown if these odontogenic tumors also show TERT promoter mutations. METHODS: Genomic DNA of paraffin-embedded ameloblastomas (n = 6) and ameloblastic carcinomas (n = 3) were Sanger-sequenced to assess the hotspot TERT promoter mutations C228T and C250T. BRAFV600E status was screened by TaqMan allele-specific quantitative polymerase chain reaction. RESULTS: None of the samples harbored TERT promoter mutations. The BRAFV600E mutation was positive in 3 of 6 of ameloblastomas and in 1 of 3 of ameloblastic carcinomas. CONCLUSION: The absence of TERT promoter mutation in the samples indicates that this molecular event is not relevant to the tumors' pathogenesis. Further studies are necessary to explore undefined genetic or epigenetic mechanisms related to TERT-upregulation in ameloblastoma, and the telomerase activity in ameloblastic carcinoma.

Adenomatoid odontogenic tumor: Features of ameloblastic-like epithelial cells differentiation, secretion, and the nature of tumor cells products.

BACKGROUND: This study aimed to investigate the differentiation of ameloblastic-like cells and the nature of the secreted eosinophilic materials in adenomatoid odontogenic tumors. METHODS: We studied histological and immunohistochemical characteristics of 20 cases using: cytokeratins 14 and 19, amelogenin, collagen I, laminin, vimentin, and CD34. RESULTS: Rosette cells differentiated into ameloblastic-like cells positioned face-to-face, displaying collagen I-positive material between them. Epithelial cells of the rosettes can differentiate into ameloblastic-like cells. This phenomenon probably occurs due to an induction phenomenon between these cells. The secretion of collagen I is probably a brief event. Amelogenin-positive areas were interspersed by epithelial cells in the lace-like areas, outside the rosettes and distant from the ameloblastic-like cells. CONCLUSIONS: There are at least two types of eosinophilic material in different areas within the tumor, one in the rosette and solid areas and another in lace-like areas. The secreted eosinophilic material in the rosettes and solid areas is probably a product of well-differentiated ameloblastic-like cells. It is positive for collagen I and negative for amelogenin, whereas some eosinophilic materials in the lace-like areas are positive for amelogenin. We hypothesize that the latter eosinophilic material could be a product of odontogenic cuboidal epithelial or intermediate stratum-like epithelial cells.

Ghost cell odontogenic carcinoma arising in dentinogenic ghost cell tumor, peripheral: A case report.

Ghost cell odontogenic carcinoma (GCOC) is an extremely rare intraosseous malignant odontogenic tumor with prominent ghost cell keratinization and dentinoid formation. Here, we present the first case of GCOC arising in dentinogenic ghost cell tumor (DGCT), peripheral. The patient was a man in his 60s with an exophytic mass in the anterior part of lower gingiva. The resected tumor measured 4.5 cm in maximum diameter. Histologically, the nonencapsulated tumor proliferated in the gingiva without bone invasion. It was predominantly composed of ameloblastoma-like nests and islands of basaloid cells with ghost cells and dentinoid in the mature connective tissue, suggesting DGCT, peripheral. As minor components, sheets of atypical basaloid cells and ameloblastic carcinoma-like nests with pleomorphism and high proliferative activity (Ki-67 labeling index up to 40%) consistent with malignancy were identified. CTNNB1 mutation and ß-catenin nuclear translocation were observed in both benign and malignant components. Final diagnosis was GCOC arising in DGCT, peripheral. GCOC shows similar histological features to DGCT. In this unique case without invasion, the cytological atypia and high proliferative activity supports the diagnosis of malignant transformation from DGCT.

Central Granular Cell Odontogenic Tumor: A Literature Review of Cases Reported in the Last 71 Years with a New Case Report.

Central granular cell odontogenic tumors (CGCOTs) are rare, benign, slowly growing odontogenic neoplasms. Due to their uncertain histogenesis, CGCOTs are still not included as a distinct entity in the WHO classification (2017) of odontogenic tumors. We report a case of CGCOT involving the right side of maxillary anterior region of a 39-year-old white female. Immunohistochemical staining showed that granular cells positively expressed CD68 and vimentin, and negatively expressed S-100 protein. Meanwhile, we searched PubMed, Google Scholar, and Scopus databases to summary the clinico-pathological features of 51 reported cases of CGCOT. The results showed that the granular cells of 28.6% cases were immunopositive for vimentin and CD68, and odontogenic epithelial cells were positive immunoreactivity for cytokeratin. These findings reinforced the mesenchymal origin of granular cells and the odontogenic nature of epithelium islands.

[Primordial odontogenic tumor in children]. / Pervichnaya odontogennaya opukhol' u detei.

Primordial odontogenic tumor (POT) is a rare benign mixed epithelial and mesenchymal odontogenic tumor that has been included as a new nosological form in the latest classification of the World Health Organization (WHO 2017). The first two clinical cases of POT treatment in children in Russia are presented. A comprehensive examination and surgical treatment of POT were carried out. The diagnosis was confirmed morphologically. OBJECTIVE: To inform maxillofacial surgeons and dentists about the clinical, radiological and morphological features of POT on the example of clinical experience and literature data.

Identification of circ_0089153/miR-608/EGFR p53 axis in ameloblastoma via MAPK signaling pathway.

OBJECTIVES: This study investigated the role of circular RNAs (circRNAs) in the pathogenesis of ameloblastoma (AB), identifying potential novel targets for future targeted therapy. MATERIALS AND METHODS: CircRNA and microRNA (miRNA) profiling in AB were built with microarrays. Six novel circRNAs were validated, circ-miRNA networks were delineated. Hsa-miR-608 was filtered over cross-comparison between database screening, miRNA microarray and validated. Circ-miRNA binding sponge was validated via luciferase reporter assay. Downstream mRNAs were screened. Regulation between miRNAs and mRNAs was confirmed in vitro. Gene interaction networks and circRNA-miRNA-mRNA interaction pathway enrichment analyses were established. RESULTS: Six differentially expressed circRNAs were selected and validated. According to miRNAs and pathways predicted, six correlated miRNAs were selected, hsa-miR-608 was filtered and validated. The hsa_circ_0089153/hsa-miR-608 binding sponge was validated. Downstream gene interaction networks showed that EGFR and p53 had the strongest co-expression. In vitro transfection results confirmed the suppressive function of miR-608 and EGFR p53. Hsa_circ_0089153/hsa-miR-608/EGFR p53 interaction pathway enrichment analysis confirmed functions mainly enriched in MAPK and related signaling pathways regulating AB progression. CONCLUSIONS: Six novel circRNAs were identified. Hsa_circ_0089153/hsa-miR-608 sponging was validated, hsa-miR-608 downregulated EGFR and p53, which might further regulate cell proliferation, differentiation, apoptosis, and cell cycle processes via the MAPK signaling pathway.

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.

Primary intraosseous carcinoma in the pediatric and adolescent mandible.

BACKGROUND: Primary intraosseous carcinoma (PIOC) is a rare malignant odontogenic tumor that predominantly occurs in males older than 50 years. PIOC can be misdiagnosed as odontogenic cyst because it occasionally shows a well-defined border on radiography. In this study, related literatures of pediatric and adolescent PIOC cases were analyzed under strict PRISMA guidelines along with an adolescent case who was provisionally misdiagnosed as an odontogenic cyst. METHODS: All case reports for PIOC published in English from 1966 to 2021 were collected. Cases under the age of 20 were classified as pediatric and adolescent populations in this study. A total of 12 pediatric and adolescent cases including 11 PIOCs from the literature and one new case of a 14-year-old female were analyzed. Clinical and radiographic features, diagnosis and treatment approaches, and prognosis were investigated. RESULTS: Ages ranged from 4 to 18 years. The female to male ratio was 1.4:1. Seven cases occurred in the mandible. Swelling was observed in 11 patients. The radiologic borders were well-defined in six cases and corticated in four cases. Tooth displacement and root resorption were observed in four and six cases, respectively. The provisional diagnosis for seven patients was odontogenic cyst and enucleation was performed in six cases including the new case. During the follow-up period, local recurrence occurred in three patients. The pediatric and adolescent PIOC cases with local recurrence showed poor prognosis. The locally recurred lesion in the new case did not decrease in size despite concurrent chemo-radiation therapy. CONCLUSIONS: Three-dimensional imaging modalities and incisional biopsy with multiple specimens are necessary to rule out PIOC in the lesions with atypical radiographic findings. PIOC should be diagnosed differentially from odontogenic cyst even in pediatric and adolescent populations to properly manage the disease with poor prognosis.

Central granular cell odontogenic tumor of mandible in a child.

Central granular cell odontogenic tumor (CGCOT) is sporadic benign odontogenic tumor and it especially occurs in women older than 50 years of age. Radiologically it manifests as unilocular to the multilocular radiolucency with sometimes mixed densities. Histopathology displays sheets and islands of large eosinophilic cells with abundant granular cytoplasm, however few cases exhibit inadequate epithelium, thus creating a diagnostic confusion. Though, resection is advocated by some surgeons, however because of the non-aggressive biological behaviour, enucleation or curettage is the treatment of choice for this lesion. Till now only 39 cases have been reported in the past six decades. We are reporting the first case of CGCOT occurring in the youngest age of eleven-year-old patient with massive size of 11 × 7 × 6 cm. This would add CGCOT as a differential diagnosis in the bony lesions of younger individuals. In addition, the importance of immunohistochemistry studies in cases with scarce odontogenic epithelium and the potential role of Carnoy's solution in the management of this rare tumor in this age group was emphasized.

New diagnostic molecular markers and biomarkers in odontogenic tumors.

Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of odontogenic tumors is not exactly determined and pathologists deal with challenges in diagnosis of odontogenic tumors because they are rare and obtained experiences are difficult to evaluate. In this study, we describe immunohistochemical and molecular markers in diagnosis of odontogenic tumors besides advanced diagnostic technique. Immunohistochemical features of odontogenic tumors beside the clinical features and radiological finding can help us to determine the correct diagnosis. Although these markers are neither specific nor sensitive enough, but analysis of gene expression provides definitive confirmation of diagnosis. In addition, "-omics" technology detected specific molecular alternation associated with etiology such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. The post transcriptional events such as DNA methylation and chromatin remodeling by histone modification affect the changes in epigenome. Furthermore, non-coding RNAs like micro-RNAs, long noncoding RNA (lncRNA) and small non-coding RNA (snoRNA) play regulatory role and impact odontogenesis. Molecular marker propose their potential role in etiopathogenesis of odontogenic tumors and suitable candidate in diagnostic, prognostic and therapeutic approaches in addition to patient management. For future evaluations, organoid represents in vitro tumor model-study for tumor behavior, metastasis and invasion, drug screening, immunotherapy, clinical trial, hallmarks association with prognosis and evolution of personalized anti-cancer therapy. Moreover, organoid biobank help us to check genetic profile. We think more investigation and studies are needed to gain these knowledges that can shift therapeutic approaches to target therapy.