Clinicopathological and molecular insights into odontogenic tumors associated with syndromes:A comprehensive review

The association between genetic syndromes and odontogenic tumors encompasses several entities,reflecting the intricate interplay between genetic factors and the development of these lesions.The present study aimed to comprehensively investigate the associations between genetic syndromes and odontogenic tumors.We delineated the diverse spectrum of syndromic connections,including key syndromes such as Gardner syndrome,Gorlin syndrome,Schimmelpenning syndrome,and others.Our findings underscore the clinical significance of recognizing odontogenic tumors associated with genetic syndromes as diagnostic indicators for early intervention.We advocate for multidisciplinary collaboration among clinicians,geneticists,and researchers to deepen our understanding of the underlying mechanisms driving these syndromic associations.In light of this,our study contributes to the growing body of knowledge in dentistry and medical genetics,offering insights that may inform clinical practice and enhance patient care for individuals affected by genetic syndromes and odontogenic tumors.

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.

Sclerosing odontogenic carcinoma of maxilla:A case report

BACKGROUND Sclerosing odontogenic carcinoma is a rare primary intraosseous neoplasm that was featured recently as a single entity in the World Health Organization classification of Head and Neck Tumors 2017,with only 14 cases published to date.The biological characteristics of sclerosing odontogenic carcinoma remain indistinct because of its rarity;however,it appears to be locally aggressive,with no regional or distant metastasis reported to date.CASE SUMMARY We reported a case of sclerosing odontogenic carcinoma of the maxilla in a 62-year-old woman,who presented with an indolent right palatal swelling,which progressively increased in size over 7 years.Right subtotal maxillectomy with surgical margins of approximately 1.5 cm was performed.The patient remained disease free for 4 years following the ablation surgery.Diagnostic workups,treatment,and therapeutic outcomes were discussed.CONCLUSION More cases are needed to further characterize this entity,understand its biological behavior,and justify the treatment protocols.Resection with wide margins of approximately 1.0 to 1.5 cm is proposed,while neck dissection,post-operative radiotherapy,or chemotherapy are deemed unnecessary.

Calcifying Odontogenic Cyst of the Oral Cavity: A Clinical Case and Current Updates on the Ethiopathogenesis

Background: The calcifying odontogenic cyst (COC) is a rare pathological entity. It falls into a group of lesions with calcifications that present benign and sometime malignant tumor variants. Case Presentation: In the present study, we report on a case of intraosseous/intrasinusal COC with impacted maxillary canine and dentinoid structures odontoma-like. The clinical, radiographical, histopathological, and molecular characteristics of this pathological entity are discussed in relation also to the problems of differential diagnosis, treatment, and prognosis. Conclusion: The true COC is a rare entity in the oral cavity and represents about less than 1% of all odontogenic lesions. Careful clinical, instrumental and histological analysis must be performed for odontogenic cysts in order to accomplish the correct surgical act and to avoid recurrence.

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.

Adenomatoid odontogenic tumour displacing multiple teeth in an adolescent

Adenomatoid odontogenic tumor is an unusual benign neoplasm which shares clinical and radiographic characteristics with odontogenic cystic lesions denoting a distinct behavior. This paper reports a case of a 12-year-old boy with a bony consistence tumefaction involving the area from teeth 12 to 17. Radiographically, the lesion was characterized by a well-circum- scribed unilocular radiolucent area displacing maxillary canine, first and second premolars. The final diagnosis was adenomatoid odontogenic tumour. The lesion was enucleated concomitantly with the removal of the canine tooth under general anesthesia. The patient was submitted to orthodontic treatment and has been followed-up for four years. Clinical and radiographic features are discussed in this report.

KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells

Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.

TET1 knockdown inhibits the odontogenic differentiation potential of human dental pulp cells

Human dental pulp cells （hDPCs） possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 （TET1） is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TETl-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration.

Identification of the involvement of LOXL4 in generation of keratocystic odontogenic tumors by RNA-Seq analysis

Keratocystic odontogenic tumors （KCOT） are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density （MVD） than dentigerous cysts （DC） and normal oral mucosa. To identify genes in the stroma of KCOT involved in tumor development and progression, RNA sequencing （RNA-Seq） was performed using samples from KCOT and primary stromal fibroblasts isolated from gingival tissues. Seven candidate genes that possess a function potentially related to KCOT progression were selected and their expression levels were confirmed by quantitative PCR, immunohistochemistry and enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 （LOXL4）, the only candidate gene that encodes a secreted protein, was enhanced at both the mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal fibroblasts compared to control tissues and primary fibroblasts （P〈0.05）. In vitro, high expression of LOXL4 could enhance proliferation and migration of the human umbilical vein endothelial cells （HUVECs）. There was a significant, positive correlation between LOXL4 protein expression and MVD in stroma of KCOT and control tissues （r=0.882）. These data suggest that abnormal expression of LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the locally aggressive biological behavior of KCOT.

Ghost cell odontogenic carcinoma of the jaws: Report of two cases and a literature review

BACKGROUND Ghost cell odontogenic carcinoma(GCOC) is a rare malignant odontogenic epithelial tumor with features of benign calcifying odontogenic cysts. Herein, we report two new cases of GCOC and systematically review the previous literature.CASE SUMMARY In case 1, a 46-year-old man complained of painless swelling of the right maxilla for 3 years, with a 1-mo history of hemorrhinia in the right nasal cavity. In case 2,a 72-year-old man was referred to our hospital with a chief complaint of painful swelling of the right mandible. Initially, the preliminary diagnoses were ameloblastomas. Thus, the two patients underwent resection of the tumor under general anesthesia. Finally, immunohistochemical examination confirmed the diagnosis of GCOC. The patient in case 1 was followed for 2 years, with no evidence of recurrence. However, the patient in case 2 was lost to follow-up.CONCLUSION GCOC is a rare malignant odontogenic epithelial tumor with high recurrence.Local extensive resection is necessary for the definitive treatment of GCOC.

Identification of Known and Novel PTCH Mutations in Both Syndromic and Non-syndromic Keratocystic Odontogenic Tumors

Aim To clarify the role of PTCH in patients with NBCCS- related and non-sydromic keratocystic odontogenic tumors. Methodology Mutation analysis was undertaken in 8 sporadic and 4 NBCCS-associated KCOTs. Results Four novel and two known mutations were identifled in 2 sporadic and 3 syndromic cases, two of which being germline mutations （c.2179delT, c.2824delC） and 4 somatic mutations （c.3162dupG, c.1362-1374dup, c.1012 C〉T, c.403C〉T）. Conclusion Our findings suggest that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic KCOTs.

Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

We present an uncommon case （female patient aged 59 years） of the clear-cell variant of calcifying epithelial odontogenic tumor （CEOT） （also known as Pindborg tumor） in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.

Fascial space odontogenic infections: Ultrasonography as an alternative to magnetic resonance imaging

BACKGROUND The introduction of modern diagnostic tools has transformed the field of maxillofacial radiology.Odontogenic infection and fascial space involvement have been evaluated with many diagnostic tools,including ultrasonography(USG)and magnetic resonance imaging(MRI).AIM To explore USG as an alternative model to MRI in the detection of fascial space spread of odontogenic infections.METHODS Among 20 patients,50 fascial spaces were clinically diagnosed with odontogenic infection and included in this prospective study.Fascial space infection involvement was examined by USG and MRI.Results were compared for both and confirmed by microbiological testing.RESULTS Ultrasonography identified 42(84%)of 50 involved fascial spaces.Whereas MRI identified all 50(100%).USG could stage the infections from edematous change to cellulitis to complete abscess formation.CONCLUSION MRI was superior in recognizing deep fascial space infections compared to USG.However, USG is a significant addition and has a definite role in prognosticatingthe stage of infection and exact anatomic location in superficial space infections.

Enucleation combined with guided bone regeneration in small and medium-sized odontogenic jaw cysts

BACKGROUND The odontogenic jaw cyst is a cavity containing liquid,semifluid or gaseous components,with the development of the disease.In recent years,with the rapid development of oral materials and the transformation of treatment of jaw cysts,more options are available for treatment of postoperative bone defect of jaw cysts.Guided bone regeneration(GBR)places biomaterials in the bone defect,and then uses biofilm to separate the proliferative soft tissue and the slow-growing bone tissue to maintain the space for bone regeneration,which is widely used in the field of implantology.AIM To observe the clinical effect of GBR in repairing bone defect after enucleation of small and medium-sized odontogenic jaw cysts.METHODS From June 2018 to September 2020,13 patients(7 male,6 female)with odontogenic jaw cysts were treated in the Department of Oral Surgery,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.Adults without hypertension,heart disease,diabetes or other systemic diseases were selected.The diagnosis was based on the final pathological results:11 cases were diagnosed as apical cysts,one as primordial cyst,and one as dentigerous cyst.The lesions were located in the maxilla in seven cases,and in the mandible in six cases.All cases were treated with the same method of enucleation combined with GBR.RESULTS Three to four months after the operation,the boundary between the implant site and the surrounding normal stroma was not obvious in patients with small-sized odontogenic jaw cysts.The patients with tooth defects were treated with implant after 6 mo.For the patients with medium-sized odontogenic jaw cysts,the density of the center of the implant area was close to the normal mass at 6 mo after surgery,and there was a clear boundary between the periphery of the implant area and the normal mass.The boundary between the periphery of the implant area and the normal mass was blurred at 8-9 mo after surgery.Patients with tooth defects were treated with implants at>6 mo after the operation.CONCLUSION Enucleation combined with guided bone regeneration in small and medium-sized odontogenic jaw cysts can shorten the time of osteogenesis,increase the amount of new bone formation,reduce complications,and improve quality of life.

Chronic progression of recurrent orthokeratinized odontogenic cyst into squamous cell carcinoma:A case report

BACKGROUND Orthokeratinized odontogenic cyst (OOC) is a benign odontogenic cyst. It is a variant of the common odontogenic keratocyst (OKC). This case report describes a rare malignant transformation of OOC, with the aim of raising awareness of the malignant potential of OOC and distinguishing it from OKC. CASE SUMMARY In August 2018, a 52-year-old man was referred to the Department of Oral Maxillofacial and Head–Neck Oncology of Wuhan University. The patient presented with severe pain in the left mandible for 2 mo, and had a 5-year history of osteomyelitis and mandibular cyst with three recurrences. His latest diagnosis by pathological examination was OOC of the left mandible with mild-tomoderate local proliferation. However, the cyst showed malignant potential by radiographic examination. We performed partial mandibulectomy and sent the lesion tissue for pathological examination. As expected, the cyst had deteriorated to moderately differentiated squamous cell carcinoma. During postoperative follow-up, the patient went for chemotherapy in September 2018 and successfully completed four cycles. CONCLUSION Surgeons should be more aware of OOC, which is usually benign but can become malignant.

Unusual presentation of localized gingival enlargement associated with a slow-growing odontogenic myxoma

Unusual presentation of localized gingival enlargement associated with a subjacent tumoural pathology is reported.The patient was a55-year-old black male,whose chief complaint was a progressive gingival overgrowth for more than ten years,in the buccal area of the anterior left mandible.According to the clinical features and the radiological diagnosis of odontogenic keratocyst,a conservative surgery with enucleation and curettage was performed.Tissue submitted for histopathological analysis rendered the diagnosis of odontogenic myxoma.After 12-month of follow-up,no evidence of recurrence was found.Clinicians should be cautious when facing any gingival enlargement to avoid diagnostic pitfalls and to indicate the appropriate treatment.

THE EOSINOPHILIC MATERIAL IN ADENOMATOID ODONTOGENICTUMOR ASSOCIATED WITH AMYLOID PROTEIN COMPONENT

Objective: To investigate the relation between eosinophilic materials and amyloid P (AP) component in adenomatoid odontogenic tumor (AOT). Methods: The expression of amyloid proteins and basement membrane proteins, including type IV collagen, laminin and heparin sulfate proteoglycan (HSPG), in AOT were analyzed by immunohistochemical method. Results: Most eosinophilic droplets among tumor cells and some epithelial cells showed positive stain for AP component. The immunoreactions of type IV collagen and laminin were only found in blood vessels of this tumor. The tumor cells and eosinophilic materials in duct-like structures were constantly unstained for both amyloid and basement membrane proteins. Present results suggest that the nature and composition of eosinophilic droplets may differ from the eosinophilic layer in ductlike structures. This study first demonstrated that the amyloid-like deposition in AOT is associated with AP component by immunohistochemical method. It supported that AP component may be epithelial origin since the AP immunolocalization was found in tumor cells.

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.

Reduced delay in diagnosis of odontogenic keratocysts with malignant transformation:A case report

BACKGROUND In rare cases,odontogenic keratocysts(ODs)transform into squamous cell carcinoma.Intervals between the first attendance of a patient and the diagnosis of OD with malignant transformation vary from weeks to years.In this article,we report a case of malignancy derived from OD with a five-day delay in diagnosis.CASE SUMMARY A 54-year-old woman was referred to Tongji Hospital in Wuhan,China with complaints of moderate pain,recurrent swelling,and pus discharge around her left maxillary lateral incisor for over 10 years.Physical examination revealed a fistula at the palatine-side mucoperiosteum of the left maxillary lateral incisor and enlarged lymph node in the left neck.Cone beam computed tomography revealed a cystic lesion with massive bone destruction from the left maxillary central incisor to the left secondary maxillary premolar and local bony destruction in the left first mandibular molar.The patient was clinically diagnosed with OD.Enucleation rather than marsupialization was performed given the risk factors of long history,recent aggravated pain,and massive bony destruction.Malignant transformation of OD was confirmed by pathologists 3 d after the operation.Radical surgery was performed,and lymph node metastasis was observed.The patient was subjected to postoperative radiotherapy and synchronous chemotherapy,and no local recurrence or distant metastasis was noted at one-year follow-up.CONCLUSION Our case suggests that clinicians should be aware of the malignant transformation of OD,especially when patients present with a long history,massive cyst,chronic inflammation,recent persistent infections,aggravated pain,numbness around the cystic lesion,and lymph node enlargement.

A Large Calcifying Cystic Odontogenic Tumor Occupying the Maxillary Sinus: A Case Report and Review of Literature

Calcifying cystic odontogenic tumor (CCOT) is an uncommon benign cystic neoplasm of the jaw that develops from the odontogenic epithelium. It is clinically characterized as a painless—slow-growing tumor that affects the maxilla as well as the mandible, and generally occurs in young adults in the third or fourth decade of life. Herein, we present the case of a 16-year-old Japanese boy who showed a CCOT in the maxillary sinus. Panoramic radiography showed a unilocular lesion in the left maxillary sinus. Computed tomography showed an approximately 5-cm well-defined unilocular expansile lesion with multiple radiopaque calcific specks, arising from the left maxillary alveolar ridge. The lesion was surgically removed, under general anesthesia, and the patient was followed up for 3 years after the surgery, and there have not been any signs of recurrence.