Dentinogenic Ghost Cell Tumor Research Articles

Calcifying Odontogenic Cyst Demonstrates Recurrent WNT Pathway Mutations and So-Called Adenoid Ameloblastoma-Like Histology: Evidence Supporting Its Classification as a Neoplasm

Calcifying odontogenic cyst (COC), once called calcifying cystic odontogenic tumor, is classified under the category of odontogenic cysts. However, the proliferative capacity of the lesional epithelium and consistent nuclear β-catenin expression raise questions about its current classification. This study aimed to determine whether COC would be better classified as a neoplasm in the histologic and molecular context. Eleven odontogenic lesions diagnosed as COC or calcifying cystic odontogenic tumor were included in this study. The growth patterns of the lesional epithelium were analyzed histologically in all cases. β-catenin immunohistochemistry and molecular profiling using Sanger sequencing and whole-exome sequencing were performed in 10 cases. Of the 11 cases studied, histologic features reminiscent of so-called adenoid ameloblastoma were observed in 72.7% (8/11), and small islands of clear cells extended into the wall in 36.4% (4/11). Intraluminal and/or mural epithelial proliferation was found in 72.7% of the cases (8/11). Nuclear β-catenin expression was observed focally in all 10 cases studied, mainly highlighting epithelial cells forming morules and adjacent to dentinoid. CTNNB1 hotspot mutations were detected in 60.0% of the cases (6/10). All the remaining cases had frameshift mutations in tumor-suppressor genes involved in the WNT pathway, including APC and NEDD4L. Recurrent WNT pathway mutations leading to nuclear translocation of β-catenin and distinct epithelial growth patterns found in COC are the neoplastic features shared by its solid counterpart, dentinogenic ghost cell tumor, supporting its classification as a tumor rather than a cyst.

Dentinogenic Ghost Cell Tumor: An Unusual Aggressive Oral Lesion

The purpose of this report was to document a case with a 1-week and 2-month follow up and contribute to the small body of existing literature to better understand this rare odontogenic tumor. There have been few aggressive and large dentinogenic ghost cell tumor case reports found in this literature.

Adenoid Ameloblastoma Shares Clinicopathologic, Immunohistochemical, and Molecular Features With Dentinogenic Ghost Cell Tumor: A Comparative Analysis.

The updated classification of odontogenic tumors by the World Health Organization (WHO) has included adenoid ameloblastoma (AA) as a distinct entity. However, distinguishing between AA and dentinogenic ghost cell tumor (DGCT) can still be challenging due to their significant morphologic similarities. In this study, we aimed to compare the clinicopathologic, immunohistochemical, and molecular characteristics of AA and DGCT to aid in their differentiation and to shed light on their pathologic mechanisms. Thirteen cases of AA and 14 cases of DGCT (15 samples) were analyzed, along with 11 cases of adenomatoid odontogenic tumor (AOT) and 18 cases of conventional ameloblastoma (AM) for comparative purposes. The study found that AA and DGCT shared a similar long-term prognosis. Immunohistochemically, all cytokeratins detected, except CK8/18, were not statistically significant in differentiating AA and DGCT, while there was a statistically significant difference in the immunophenotype of CK7 and CK10/13 between AA and AM. Nuclear β-catenin accumulation were detected in all cases of AA and DGCT, while AOTs and AMs exhibited cytoplasmic β-catenin. Molecularly, CTNNB1 hotspot mutations were found in only 1 case of AA (1/13), but not found in the other 3 types of tumors. BRAF p.V600E mutation was positive in 2/13 (15%) AA, 1/15 (7%) DGCT, and 2/11 (18%) AOT cases. In comparison, conventional AM was positive for BRAF p.V600E mutation in 94% (17/18) of cases, while KRAS mutations were detected in 63% (7/11) of AOT cases. The study suggests that the so-called AA is a rare benign tumor that exhibits clinical, immunohistochemical, and molecular features similar to DGCTs. Based on these findings, AA should not be categorized as a standalone entity solely based on the presence of whorls/morules and cribriform/duct-like structures. Further studies are needed to investigate the pathologic mechanisms of these tumors and to identify potential therapeutic targets.

Dentinogenic ghost cell tumour: A case report

A 23-year-old Malay female patient presented with a history of pain and swelling over right maxilla. Imaging showed a well-defined unilocular radiolucency with areas of radiopacity in the right maxilla. The lesion was initially thought to be a unicystic ameloblastoma. However, histopathology of the excised lesion proved otherwise with a final diagnosis given as dentinogenic ghost cell tumour. The clinical presentation of the case, subtypes of DGCT, similarities with ameloblastoma, and treatment modalities are discussed in this paper.

Dentinogenic ghost cell tumor revisited from a single institution in China with focus on adenoid ameloblastoma-like features

ObjectiveThe present study aims to identify adenoid ameloblastoma (AdAM) from previously diagnosed cases of dentinogenic ghost cell tumor (DGCT), and gain insight to the possible relationship between AdAM and DGCT. MethodsDGCT cases diagnosed between 2006 and 2022 were re-examined with focus on the AdAM-like features. ResultsA total of nine patients were included. Seven patients were males and two were females. The mean age was 38.0 ± 16.0 years. Five tumors occurred in the maxilla and four in the mandible, with a remarkable predilection for the posterior regions of both jaws. Microscopically, dentinoid material deposition was present in all cases. The ghost cells were absent in two cases. Rare ghost cells (<1%) were observed in three cases, and a higher proportion of ghost cells (5%-20%) were present in the remaining four cases. All cases showed prominent AdAM-like features, including duct-like structures, whorls/morules, and cribriform architecture. According to the diagnostic criteria proposed by the 2022 WHO classification, five cases without or with rare ghost cells were reclassified as AdAM. The other four cases including a higher proportion of ghost cells consisted of a mixture of DGCT and AdAM histopathologic patterns. ConclusionOur results confirmed that the AdAM-like features had been largely overlooked in the diagnosis of DGCT at our institution in the past. Whilst a subset can now be more accurately classified as AdAM, some tumors showed overlapping morphological features between AdAM and DGCT, suggesting that the two may represent a spectrum of the same entity.

Dentinogenic ghost cell tumor associated with odontoma: report of a rare case and review of literature.

Dentinogenic ghost cell tumor (DGCT) is an uncommon odontogenic tumor considered to be the solid, tumorous variant of calcifying odontogenic cyst (COC). DGCT is characterized by islands of ameloblastoma-like epithelial cells that resemble the enamel organ, the presence of ghost cells, and dentinoid material. Here, we report a rare case of dentinogenic ghost cell tumor associated with an odontoma in an adult patient and conduct a review of the literature. To the best of our knowledge, there have only been 4 case reports of DGCT associated with odontoma, all of which occurred in children and adults younger than 30 years old.

Modifications of Gallego staining and its dental application.

The objectives of the study are to employ modified Gallego staining in pathology and to specifically evaluate the hard tissue apposed to odontogenic epithelium in order to aid in the diagnosis. Lillie's modification of Gallego's stain was utilized as a reference to create a fresh batch of the stain. The archival and running cases of 2021-2022 was screened for odontogenic pathologies, yielding approximately 46 cases, among these four cases were selected which required evaluation of the hard tissue matrix apposed to odontogenic epithelium for its characterization. The modified Gallego staining was employed in the soft tissue sections of these cases under controlled environment. The staining results were evaluated. The stain was used in cases to stain dentinoid deposition as green color in hybrid ameloblastoma, archegonous cystic odontoma, dentinogenic ghost cell tumor and also in other cases like calcifying odontogenic cyst. Bone presented as green in color, cells as pink color and collagen as green-pink. This helped in the correct diagnosis of these cases facilitating the correct treatment modality. In the field of oral pathology, there are a multitude of lesions which are odontogenic with the diagnosis of few of them hinging on the characterization of hard tissue matrix found in close approximation to odontogenic epithelium implying an inductive capability to the odontogenic epithelium. This particular modified Gallego stain has been able to help in diagnosis of few such cases in our repertoire of cases.

Dentinogenic ghost cell tumor treated with a combination of marsupialization and radical resection: a case report and review of the literature

BackgroundDentinogenic ghost cell tumor is a rare benign tumor that accounts for less than 3% of all cases and consists of the stellate reticulum, which is made up of enamel epithelioid and basaloid cells. Although DGCT is a benign tumor, the local infiltration of the odontogenic epithelium or recurrences have been reported, and its detailed pathology and treatments remain unclear.Case presentationThis report describes the case of a 60-year-old Japanese male diagnosed with a maxillary dentinogenic ghost cell tumor. Images showed well-circumscribed, multilocular cystic lesions with a calcified substance in the interior. Marsupialization was performed along with biopsy to prevent the expansion of the lesion, and a partial maxillectomy was performed 2 years after the initial examination. Histopathological findings showed ameloblastomatous proliferation containing clusters of ghost cells and dentinoid materials, resulting in the diagnosis of dentinogenic ghost cell tumor. This article also reviews recently reported cases of dentinogenic ghost cell tumor.ConclusionIt is important to perform marsupialization, proper resection, and postoperative follow-up because of possible recurrence.

Dentinogenic Ghost Cell Tumour in Childhood Involving the Temporomandibular Joint: Considerations and Therapy.

Although the uncommon dentinogenic ghost cell tumour (DGCT) is a benign entity, it possesses the ability to cause widespread destruction of the jaws and to recur after bone-preserving therapy. Hence, clear margins should be achieved upon surgery, and reconstruction techniques must often be used to restore osseous defects. However, this can be challenging in cases with involvement of the temporomandibular joint (TMJ), and especially in children. We present a case of a DGCT in a 12-year-old boy with wide infiltration of the mandible and the TMJ. A two-staged reconstructive approach was performed. Upon primary surgery, tumour-free margins were obtained and mandibular anatomy was restored using an iliac crest graft and an alloplastic condyle implant for temporary TMJ reconstruction. In a second step 5months later, having received a customized TMJ prosthesis consisting of a fossa and a condyle component, the TMJ was completely replaced for definitive reconstruction. A customized TMJ prosthesis could be a solution for reconstruction of the TMJ in children. However, the further course with respect to growth disturbances must be evaluated upon short-term follow-ups and might require additional corrective interventions.

The molecular basis of odontogenic cysts and tumours.

The advances in molecular technologies have allowed a better understanding of the molecular basis of odontogenic cysts and tumours. PTCH1 mutations have been reported in a high proportion of odontogenic keratocyst. BRAF p.V600E are recurrent in ameloblastoma and KRAS p.G12V/R in adenomatoid odontogenic tumour, dysregulating the MAPK/ERK pathway. Notably, BRAF p.V600E is also detected in ameloblastic carcinoma, but at a lower frequency than in its benign counterpart ameloblastoma. Recently, adenoid ameloblastoma has been shown to be BRAF wild-type and to harbour CTNNB1 (β-catenin gene) mutations, further suggesting that it is not an ameloblastoma subtype. CTNNB1 mutations also occur in other ghost-cell-containing tumours, including calcifying odontogenic cysts, dentinogenic ghost cell tumours and odontogenic carcinoma with dentinoid, but the link between CTNNB1 mutations and ghost cell formation in these lesions remains unclear. Regarding mixed tumours, BRAF p.V600E has been reported in a subset of ameloblastic fibromas, ameloblastic-fibrodentinomas and fibro-odontomas, in addition to ameloblastic fibrosarcoma. Such mutation-positivity in a subset of samples can be helpful in differentiating some of these lesions from odontoma, which is BRAF-wild-type. Recently, FOS rearrangements have been reported in cementoblastoma, supporting its relationship with osteoblastoma. Collectively, the identification of recurrent mutations in these aforementioned lesions has helped to clarify their molecular basis and to better understand the interrelationships between some tumours, but none of these genetic abnormalities is diagnostic. Since the functional effect of pathogenic mutations is context and tissue-dependent, a clear role for the reported mutations in odontogenic cysts and tumours in their pathogenesis remains to be elucidated.

Adenoid Ameloblastoma Shares Clinical, Histologic, and Molecular Features With Dentinogenic Ghost Cell Tumor: The Histologic Spectrum of WNT Pathway–Altered Benign Odontogenic Tumors

An epithelial odontogenic tumor called adenoid ameloblastoma (AA) has recently been included in the new WHO classification. However, AA has considerable overlapping features with a preexisting entity, dentinogenic ghost cell tumor (DGCT). This study compared the clinical, histologic, and molecular characteristics of AA and DGCT. Eight cases of odontogenic tumors initially diagnosed as AA or DGCT were included in this study. Quantitative histologic analysis, β-catenin immunohistochemistry, and molecular profiling using next generation sequencing were performed. Additionally, accumulated clinical data of AA and DGCT were statistically analyzed. Nuclear β-catenin accumulation was detected in all cases in common, although the tumors studied histologically consisted of varying combinations of the AA-like phenotype, ghost cells, and dentinoid. However, CTNNB1 hotspot mutations were not found in any case. Instead, loss-of-function mutations in tumor suppressor genes involved in the WNT pathway, including the APC, SMURF1, and NEDD4L genes, were found regardless of histologic type. In addition, KRT13 mutations were detected in 2 cases with a high proportion of ghost cells. Finally, a literature analysis revealed clinical similarities between the previously reported cases of AA and DGCT. These findings suggest that from a clinical and molecular point of view, AA and DGCT represent a histologic spectrum of WNT pathway–altered benign odontogenic tumors rather than 2 distinct tumors. Moreover, previously unidentified keratin mutations may be associated with ghost cell formation found in specific types of odontogenic lesions.

Dentinogenic ghost cell tumor: A case report with review of literature

Dentinogenic ghost cell tumor is a rare odontogenic neoplasm first described by Praetorious et al in 1981. It is a solid variant of calcifying odontogenic cyst. This tumor shows no gender predilection and is seen more in mandibular anterior and molar region. Clinically, this tumor presents as two forms, Intraosseous &amp; Extraosseous. Ghost cells are pathognomonic in diagnosing this tumor. Very few cases of this rare dentinogenic ghost cell tumor have been reported in the literature till date.

Dentinogenic ghost cell tumor: A case report with review of literature

Dentinogenic ghost cell tumor: A case report with review of literature

Dentinogenic Ghost Cell Tumour, a rare case of an African young female patient: Review of literature and report of a case

Dentinogenic ghost cell tumour (DGCT) is a very rare aggressive benign odontogenic tumour with high recurrence rate and a potential to transform into malignancy. It can render facial disfigurement. The tumour is most frequently encountered in males than females with a ratio of 2:1. The peak incidence is in patients aged 40 - 60 years and the posterior mandible is slightly more affected than the maxilla. Segmental resection is a recommended surgical treatment and long-term postsurgical follow up is essential. This paper discusses a case of a 20-year-old African female patient who was diagnosed with a DGCT.

DENTINOGENIC GHOST CELL TUMOR: REPORT OF THREE NEW CASES

This case series contributes with 3 new cases of dentinogenic ghost cell tumor (DGCT). Case 1 is a 44-year-old male patient with an expansive swelling in the posterior mandible of 2 years duration. It appeared as a well-defined mixed radiolucent-radiopaque (RL-RO) lesion associated with an unerupted first molar. Case 2 is a 22-year-old female patient referred for evaluation of a slow-growing asymptomatic swelling of unknown duration in the left posterior maxilla; it was a 4-cm well-defined unilocular RL-RO lesion causing resorption of adjacent molars and encroachment of the maxillary sinus. Case 3 is a 37-year-old male patient with an expansive well-defined radiolucency in the lower premolar region exhibiting root resorption. Microscopically, prominent ameloblastomatous proliferation with areas of ghost cells and dentinoid material were observed. The patients are under long-term follow-up with no signs of recurrence to date. DGCT should be microscopically distinguished from adenoid ameloblastoma with dentinoid.

DENTINOGENIC GHOST CELL TUMOR WITH FOCAL FEATURES SUGGESTING GHOST CELL ODONTOGENIC CARCINOMA: A CHALLENGING DIAGNOSIS

Dentinogenic ghost cell tumor and ghost cell odontogenic carcinoma form a spectrum of rare benign and malignant odontogenic neoplasms, respectively. A 24-year-old White woman complained of a painful enlargement and dental mobility in the maxilla for approximately 1 year. An intraoral examination showed a 3 × 3 cm firm exophytic mass in the left molar region. Tomographic sections showed a well-defined hypodense expansion with hyperdense foci inside invading the maxillary sinus. Microscopically, incisional sections showed a predominantly solid basaloid epithelium presenting atypical features, mitotic activity, ghost cells, positivity for p53, and high Ki-67 labeling, suggesting malignancy. Partial maxillectomy was performed. Surprisingly, the surgical specimen presented an important variation of the epithelial pattern and lacked any sign of malignancy, with abundant ghost cells and dentinoid, confirming the diagnosis of dentinogenic ghost cell tumor. A strict regular follow-up was done with no signs of recurrence or metastasis over 2 years.

PERIPHERAL DENTINOGENIC GHOST CELL TUMOR: CASE REPORT

Peripheral dentinogenic ghost cell tumor (DGCT) is a rare benign mixed epithelial and mesenchymal odontogenic neoplasm, with approximately 52 cases reported in the literature. A 48-year-old woman was referred for evaluation of a painless, slow-growing swelling in the mandible caused by a removable denture that evolved over 1 year. Her medical history was unremarkable. Intraoral examination showed a pinkish, firm nodule, with erythematous areas, in the left mandibular alveolar ridge. Panoramic radiographic examination revealed no signs of bone involvement. Under the diagnostic hypothesis of inflammatory fibrous hyperplasia, an incisional biopsy was performed. Histopathologic analysis disclosed sheets and islands of odontogenic epithelium, with areas closely resembling ameloblastoma. Ghost cells, dentinoid material, and inflammatory foreign body reaction with multinucleated giant cells were also observed. The final diagnosis was peripheral DGCT. Treatment consisted of surgical excision, and no signs of recurrence were detected after 2 months of clinical follow-up.

Useful diagnostic histogenetic features of ectopic odontogenic ghost cell tumours

BackgroundEctopic odontogenic tumours are rare and difficult to diagnose. Consequently, they are occasionally misdiagnosed as other tumours and overtreated. Dentinogenic ghost cell tumours (DGCTs) are odontogenic neoplasms characterised by a CTNNB1 mutation, ghost cell appearance, and dentinoid-like calcification. Herein, we present a case of ectopic DGCT on the floor of a patient’s mouth, providing reliable clinicopathological and genetic evidence of its odontogenicity for the first time.Case presentationA 72-year-old man presented with painless sublingual swelling. Imaging revealed a multi-lobulated, solid-cystic mass on the floor of his mouth. Cytological evaluation showed folded epithelial clusters composed of basaloid cells, keratinised material, and calcification. Histological analysis revealed a multi-cystic, cribriform to solid nest, with an odontogenic satellate reticulum-like epithelium, including ghost cells and dentinoid matrix deposition. Immunohistochemical analysis found that CK19, CK5/6, bcl-2, and p63 were diffuse positive, β-catenin was focal positive in the nuclei, and the cells in the dentinoid matrix were positive for DMP1. The CTNTTB1 mutation was detected, leading to the final diagnosis of ectopic DGCT. There was no recurrence during the 6-month follow-up.ConclusionsOverall, we have presented a comprehensive clinical overview of DGCT and identified its pathological and genetic features. This report will aid in the recognition of this rare disease in the future and help to avoid misdiagnosis and overtreatment.

Dentinogenic Ghost Cell Tumor: A Rare Case Report in Maxillary Sinus

Ghost Cell Tumors (GCT) are a class of lesions that can exist in the form of a cyst or solid neoplastic tumor, and in terms of behavior, they can be benign, locally invasive, or metastatic. They are identified by the presence of ame-loblastic epithelium, ghost cell, and calcification. These lesions are mostly prevalent in the lower jaw, anterior mandible area. They are distributed equally between the male and female population in the second, sixth, and eighth decades of life. Since the recurrence rate is very low, it seems that a conservative approach is sufficient for most cases. Here, we present a rare case of dentinogenic ghost cell tumor in the left sinus of a 32-year-old male patient. It is temporarily diagnosed through clinical findings and .radiographic scan, and later on, confirmed via histology

Comparison of b-Catenin Protein Expression in Calcifying Odontogenic Cyst and Dentinogenic Ghost Cell Tumour

Introduction: Calcifying Cystic Odontogenic Tumour (CCOT)/ Calcifying Odontogenic Cyst (COC) display a varying tissue morphology, while exhibiting different biological progression also at the same time. Attempts at classifying COC have largely been unsuccessful due to the present lack of knowledge about the development of these tumours and their underlying molecular changes. Wingless-beta catenin (Wnt–β catenin) signalling pathway has been found to be a cornerstone in the ectodermal development and tumour initiation-progression to malignant tumours, but its specific role in the pathogenesis of odontogenic ghost cell lesions is unknown. Aim: To elucidate the participation and comparison of β-catenin protein expression in pathogenesis of benign odontogenic ghost cell lesions, CCOT and Dentinogenic Ghost Cell Tumour (DGCT). Materials and Methods: A cross-sectional Immunohistochemical (IHC) study was performed in the Department of Oral and Maxillofacial Pathology, AECS Maaruti College of Dental Sciences and Research Centre, Bengaluru, Karnataka, India, from December 2019 to June 2021. Research was conducted on tissue sections of centrally located 16 cases of CCOT categorised as group 1 and four cases of DGCT categorised as group 2 using β-catenin tumour marker. The study samples were retrieved from the archives. IHC stained slides were subjected for histopathological analysis, where labelling index of tumour cells were assessed in three high power fields. Resultant β-catenin expression was compared between Benign Odontogenic Ghost Cell Lesions (BOGCL). Results were subjected to statistical analysis, Statistical Package for Social Sciences for Windows 17.0 (SPSS, Philadelphia, IL) software to analyse the data. Results: β-catenin positivity was assessed in tumour cells of both the groups, 16 CCOT (group 1) and 4 DGCT (group 2). In each case, number of cells in three high power field i.e., under 40X magnification were evaluated. Both the groups expressed membranous, cytoplasmic and nuclear positivity in the basaloid tumour cells. Whereas, ghost cells showed no reactivity to the biomarker, β-catenin. On comparison using Mann Whitney U and Wilcoxon W test, there was no statistically significant difference in β-catenin expression between CCOT and DGCT. Conclusion: β-catenin plays an important role in the tumourigenesis of benign odontogenic ghost cell lesions. Immunohistochemically CCOT and DGCT showed no significant difference in the β-catenin expression. Hence, the results suggest that CCOT and DGCT may show variation in clinical behaviour but share similar histogenesis.