Recurrence and cancerization of ameloblastoma: multivariate analysis of 87 recurrent craniofacial ameloblastoma to assess risk factors associated with early recurrence and secondary ameloblastic carcinoma

Objective: The recurrence and progression of ameloblastoma are unpredictable. Therefore, we examined the influence of clinical factors on recurrence time and analyzed the clinical factors associated with early recurrence and cancerization. We then developed a staging system to predict early recurrence and cancerization. Methods: All of the primary craniofacial ameloblastoma patients treated in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were recorded. There were 87 recurrent cases used to create a staging system and tested in a Cox regression analysis for risk factors associated with early recurrence or cancerization following surgery. Results: There were 890 craniofacial ameloblastoma patients, and 72 cases had recurrence. There were also 15 cases with cancerous recurrence. The overall recurrence rate was 9.78%, and the cancer rate was 1.69%. The primary cases were classified into the following 3 stages based on clinicopathological features: stage I, the maximum tumor diameter <= 6 cm; stage II, the maximum diameter of tumor >6 cm or tumor invasion to the maxilla sinus/orbital floor/soft tissue; and stage III, tumor invasion of the skull base or metastasis into regional lymph nodes. When the method of surgery was controlled by partial correlation, the staging had significance with recurrence time (P=0.004). The Cox analysis showed the tumor stage was correlated with recurrence time (P=0.027) and cancerization time (P=0.002). However, the surgical method did not influence the recurrence time when adjusted for cofounding variables. Conclusions: Tumor larger than 6 cm and invasion to soft tissues or adjacent anatomical structures are associated with early recurrence. This staging system can be used to predict the risk factors of early recurrence and cancerization in ameloblastoma patients.

Ameloblastic carcinoma: Report of a rare case

Ameloblastic carcinoma is a rare odontogenic tumor exhibiting histological evidence of malignancy in the primary or recurrent tumor. It is characterized by rapid, painful expansion of the jaw, unlike conventional ameloblastomas. The tumor most frequently involves the mandible. The expanding lesion causes perforation of the buccal and lingual plates of the jaw and invades the surrounding soft tissue. Rapidly growing large tumor mass may cause tooth mobility. A mandibular tumor involving the mental nerve leads to paresthesia of the nerve. A maxillary tumor can produce a fistula in the palate and paresthesia of the infraorbital nerve. Most ameloblastic carcinomas are presumed to have arisen de novo with a few cases of malignant transformation of ameloblastomas. Although rare, these lesions have been known to metastasize, mostly to the regional lymph nodes or lungs. A case of ameloblastic carcinoma in a 60-year-old man is reported here and its clinical, radiological and histological features are discussed.

An Aggressive Ameloblastic Fibroma in Maxilla of a 5-Year-Old Child—Reconstruction of the Defect with Buccal Flap Advancement—A Conservative Approach

Ameloblastic fibroma (AF) is a rare tumour of mixed odontogenic origin that can occur either in mandible or maxilla but is most frequently found in the posterior region of mandible. Age of occurrence is generally between first and second decades of life. It is often mistaken for a den tigerous cyst due to presence of an impacted tooth. The diagnosis of AF usually occurs accidentally by routine radiographic examination for an impacted tooth. Histologically it consists of odontogenic ectomesenchyme resembling the dental papilla, epithelium resembling dental lamina and enamel organ without dental hard tissues. There is controversy in the literature as to whether the treatment should be conservative or a radical resection should be done. A conservative treatment strategy, such as enucleation and curettage, is usually sufficient. We describe a case of massive ameloblastic fibroma in a 5-year-old child with an unusual position in maxillary posterior region and without any impacted tooth. Surgical resection of the tumor through Weber Ferguson approach was done under GA with 2 years of follow-up without any recurrence.

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 Pub Med,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.

Clinical management of primary odontogenic sarcoma in the mandible:a case report after WHO nomination

Ameloblastic fibro-odontosarcoma(AFOS)now designated as odontogenic sarcoma is an extremely rare odontogenic tumor,which histologically presents as a biphasic neoplasm with a malignant mesenchymal component plus ameloblastic epithelium.Here we report a 27-year-old Chinese female with the complaint of a painful swelling for half a month in the right mandible.A segmental mandibulectomy,with an immediate mandibular reconstruction using a free vascularized osteocutaneous fibular flap was performed using surgical guide models.Histological analysis revealed a primary odontogenic sarcoma.The postoperative period was uneventful,and no clinical indication of recurrence or metastasis was observed during the 3-year follow-up.No adjuvant therapy was proposed.This is the first odontogenic sarcoma case reported in China after the new World Health Organization classification of odontogenic lesions.

Mixed odontogenic tumors:A review of the clinicopathological and molecular features and changes in the WHO classification

BACKGROUND Ameloblastic fibromas and ameloblastic fibrosarcomas are rare odontogenic tumors,and controversy exists in the classification of cases presenting hard-tissue production:Ameloblastic fibrodentinoma(AFD)and ameloblastic fibro-odontoma(AFO).These cases are currently considered“developing odontomas”(hamartomatous lesions).AIM To analyze the clinicopathologic features of these lesions and discuss the changes in the 2017 World Health Organization classification.METHODS An electronic literature search was performed in the PubMed/MEDLINE database.An electronic search of the English language literature was performed and last updated in September 2020 in the PubMed/MEDLINE database using the following terms:“ameloblastic fibroma”,“ameloblastic fibrodentinoma”,“ameloblastic fibro-odontoma”,“ameloblastic sarcoma”,“ameloblastic fibrosarcoma”,“ameloblastic fibrodentinosarcoma”,“ameloblastic fibroodontosarcoma”and“odontogenic carcinosarcoma”.The inclusion criteria were odontogenic tumor series,case reports and systematic reviews that provided sufficient clinical,radiological and microscopic documentation to confirm the diagnosis.RESULTS The database search strategy resulted in 947 papers.Articles focusing on other topics,articles that were not in English,duplicate articles,and articles without fulfilling the inclusion criteria were excluded.Finally,96 publications were included in this review to describe and discuss the main features of the searched entities.Several aspects of AFO and AFD,such as biological behavior,age of occurrence,amount of hard tissue,and potential for malignant transformation into odontogenic sarcomas,support the neoplastic nature in most of the reported cases.Considering the clinical,radiographic,histopathological and molecular characteristics of odontogenic lesions with hard tissue production,we suggest that these types of lesions should continue to be recognized as odontogenic tumors by maintaining the classically used terms.CONCLUSION This recommendation will be relevant for future clinical,microscopic,and molecular studies to better understand the biology of these interesting odontogenic tumors.

TGF-β1调控成釉细胞ODAM基因表达的研究

目的:探讨TGF-β1对ODAM基因表达的作用。方法:通过实时定量RT-PCR法观察TGF-β1对成釉细胞ODAM基因表达的影响;利用c-jun小RNA干扰(siRNA)技术,阻断转录因子c-jun基因表达,观察c-jun基因沉默对TGF-β1诱导ODAM基因表达的影响;利用双荧光素酶基因报告系统研究成釉细胞中TGF-β1对ODAM启动子转录活性的调控作用。结果:TGF-β1刺激成釉细胞后,ODAM基因表达显著增强;利用小RNA干扰技术使c-jun基因沉默,实时定量RT-PCR法研究显示,TGF-β1调控ODAM基因表达的作用减弱。将pGL3-ODAM转染成釉细胞后,用TGF-β1刺激成釉细胞一定时间,ODAM启动子的转录活性增强。c-jun基因沉默抑制了TGF-β1对ODAM启动子的激活作用。结论:在釉质发育过程中,TGF-β1通过转录因子c-jun调控成釉细胞ODAM基因表达。

Meeting report:a hard look at the state of enamel research

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines （ENAMEL） Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research （NIDCR）. Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.

Globoside accelerates the differentiation of dental epithelial cells into ameloblasts

Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside （Gb4）, a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins （including neurotrophin-4） and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.

The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells

This study aimed to compare epithelial cells derived from human embryonic stem cells(hESCs) to human ameloblast-lineage cells (ALCs),as a way to determine their potential use as a cell source for ameloblast regeneration.Induced by various concentrations of bone morphogenetic protein 4(BMP4),retinoic acid(RA) and lithium chloride(LiCI) for 7 days,hESCs adopted cobble-stone epithelial phenotype(hESC-derived epithelial cells(ES-ECs)) and expressed cytokeratin 14.Compared with ALCs and oral epithelial cells(OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs.ES-ECs were compared with human fetal skin epithelium,human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well.ALCs had relatively high expression levels of cytokeratin 76,which was also found to be upregulated in ES-ECs.Based on the present study,with the similarity of gene expression with ALCs,ES-ECs are a promising potential cell source for regeneration,which are not available in erupted human teeth for regeneration of enamel.