Ghost Cell Odontogenic Carcinoma Research Articles

Challenging pitfalls in frozen section pathology: a case of mandible ghost cell odontogenic carcinoma and the literature review

BackgroundGhost cell odontogenic carcinoma (GCOC) is a rare malignancy characterized by the presence of ghost cells, preferably in the maxilla. Only slightly more than 50 case reports of GCOC have been documented to date. Due to the rarity of this tumor and its nonspecific clinical criteria, there is a heightened risk of misdiagnosis in clinical examination, imaging findings, and pathology interpretation.Case presentationA 50-year-old male patient presented to the hospital due to experiencing pain in his lower front teeth while eating for the past 2 months. Upon examination, a red, hard, painless mass was found in his left lower jaw, measuring approximately 4.0 cm × 3.5 cm. Based on the malignant histological morphology of the tumor and the abundant red-stained keratinized material, the preoperative frozen section pathology misdiagnosed it as squamous cell carcinoma (SCC). The surgical resection specimen pathology via paraffin section revealed that the tumor was characterized by round-like epithelial islands within the fibrous interstitium, accompanied by a large number of ghost cells and some dysplastic dentin with infiltrative growth. The malignant components displayed marked heterogeneity and mitotic activity. Additionally, a calcified cystic tumor component of odontogenic origin was observed. Hemorrhage, necrosis, and calcifications were present, with a foreign body reaction around ghost cells. Immunoreactivity for β-catenin showed strong nuclear positivity in tumor cells, while immunostaining was completely negative for p53. The Ki67 proliferation index was approximately 30–40%. The tumor cells exhibited diffuse CK5/6, p63, and p40 immunoreactivity, with varying immunopositivity for EMA. Furthermore, no BRAFV600E mutation was identified by ARMS-PCR. The final pathology confirmed that the tumor was a mandible GCOC.ConclusionWe have reported and summarized for the first time the specific manifestations of GCOC in frozen section pathology and possible pitfalls in misdiagnosis. We also reviewed and summarized the etiology, pathological features, molecular characteristics, differential diagnosis, imaging features, and current main treatment options for GCOC. Due to its rarity, the diagnosis and treatment of this disease still face certain challenges. A correct understanding of the pathological morphology of GCOC, distinguishing the ghost cells and the secondary stromal reaction around them, is crucial for reducing misdiagnosis rates.

Case report: Ghost cell odontogenic carcinoma in a dog: diagnostics and surgical outcome.

A 6 year-old spayed female Poodle presented with a mandibular mass. Radiographic examination revealed osteolysis from the right mandibular canine to the fourth premolar, along with horizontal bone loss and dorsal displacement of the right mandibular first and second premolars. Skull cone beam computed tomography revealed osteolysis at the level of the right mandibular canine and fourth premolar. A destructive bone lesion was observed in the apical area of the right mandibular canine, with mass invasion of the interradicular bone of the right mandibular first molar near the mandibular canal. Consequently, unilateral total mandibulectomy and skin flap surgery were performed. Histopathological examination revealed poorly demarcated and infiltrative neoplastic epithelial cells that formed small islands and trabeculae. Neoplastic cells exhibited the malignant features of cytological atypia and high mitotic activity. Furthermore, the neoplastic epithelial cells frequently showed ghost cell changes and were diagnosed as ghost cell odontogenic carcinoma (GCOC). The dog was followed up for 1 year, during which no severe complications or local recurrence was observed, except for slight mandibular drift, tongue protrusion, and drooling. This case report describes the clinical features, diagnostic imaging, and histologic features of an unreported GCOC in a dog and the favorable outcome following surgical resection.

Ghost cell odontogenic carcinoma: A rare case report and review of literature.

Ghost cell odontogenic carcinoma is a rare malignant odontogenic carcinoma characterized by the presence of ghost cells. It has a nonspecific clinical and radiographic presentation and can be locally destructive and invasive, sometimes with distant metastases. However, no effective systemic therapy is currently recommended for such patients. The patient has been unable to undergo surgery or radiotherapy again. Therefore, he was referred to our department for a more aggressive, multimodal systematic treatment program. The histopathological examination was morphologically suggestive of ghost cell odontogenic carcinomas. We report a case of locally invasive primary inoperable odontogenic shadow cell carcinoma in a 31-year-old Chinese man who achieved treatment with Toripalimab and chemotherapy, followed by Toripalimab maintenance therapy after 6 cycles. He achieved partial remission after treatment. The quality of life significantly improved after treatment. There were no grade 3/4 treatment-related adverse events during treatment. This case presented that Toripalimab and chemotherapy may be a safe and effective systemic therapy for ghost cell odontogenic carcinoma.

Ghost cell odontogenic carcinoma of the mandible: Case report and review of literature

Ghost cell odontogenic carcinoma (GCOC) is an extremely rare odontogenic carcinoma that is typically characterized by an admixture of atypical epithelial cells and ghost cells. Up to date, GCOC remains rare with around 58 cases have been reported. Herein,we report a case of GCOC of the mandible, the patient is particularly young, successfully treated with surgical resection, reconstruction, and radiation, followed for 2 years without any sign of recurrence. A comprehensive literature review was performed.

Ghost cell odontogenic carcinoma of the mandible: case report and review of literature

Ghost cell odontogenic carcinoma of the mandible: case report and review of literature

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.

Ghost cell odontogenic carcinoma: Role of p53 as predictor of progression

Ghost cell odontogenic carcinoma (GCOC) a rare malignant Odontogenic Carcinoma with an unpredictable behaviour presenting with local recurrences and distant metastases, to best of our knowledge about 38 cases have been reported in the past. This is an additional case of GCOC in a 25-year old female presented with a slow-growing mandibular swelling since 9 months with restricted jaw mobility. The CT scan showed an ill-defined osteodestructive lesion in the mandible. The histological examination confirms the diagnoses as a GCOC.
 Immunohistochemical examination was performed for Ki-67 proliferation index and p53 a predictor of progression. This case was managed by wide surgical resection of tumor and reconstruction of the defect by free fibular flap. Six months follow- up period shows no signs of recurrence. GCOC is rare Odontogenic Carcinoma with unpredictable behaviour however p53 & Ki67 proliferation index can predict the progression of tumor and help in differentiation from benign precursor lesions as early diagnosis & treatment of GCOC is necessary to prevent local recurrences & distant metastases.

Calcifying odontogenic cyst – A review

Calcifying odontogenic cyst (COC), also known as “Gorlin cyst,” is a rare developmental odontogenic lesion, introduced by Gorlin in 1962. COC exists either as a cystic or a solid variant. This lesion has been known by different names and classified into various subtypes. The World Health Organization classified (2005) COC as a neoplasm and used the term calcifying cystic odontogenic tumor for benign cystic type, the dentinogenic ghost cell tumor for the benign solid type lesions which occur centrally or peripherally, and the malignant one as ghost cell odontogenic carcinoma. COC mimics other odontogenic cysts clinically as well as radiologically, and a definitive diagnosis can be made only by histological means. The present article discusses the various terminologies, classification, histopathology, and immunohistochemistry of COC.

A case of large ghost cell odontogenic carcinoma arising in the mandible

A case of large ghost cell odontogenic carcinoma arising in the mandible

Calcifying Cystic Odontogenic Tumor Associated with a Complex Odontoma


 We present a case of a 16-year-old lad with a one year history of gingival mass of the left maxillary alveolar ridge. Excision revealed a cystic mass with brown fluid and irregular calcified material within the cavity.
 Histopathologic examination of the cyst lining shows a stratified cuboidal epithelium with palisading of the basal layer. The cells of the latter show reverse nuclear polarization reminiscent of ameloblastic epithelium. The superficial layers have a stellate reticulum-like appearance and contain large eosinophilic polygonal ghost cells. (Figure 1, 2) Some of the ghost cells show calcifications. (Figure 3) Sections from the hard, bony fragments show haphazard deposition of dentin and enamel-like material. (Figure 4) With these features, this case was called a calcifying cystic odontogenic tumour in association with a complex odontoma.
 Calcifying cystic odontogenic tumor (CCOT) is a benign neoplasm characterized by an ameloblastoma-like epithelium with ghost cells that often show calcification.1 It comprises only 2% of all benign odontogenic neoplasms.2 There is equal distribution of involvement for the maxilla and mandible, no sex predilection, with most cases diagnosed at the 2nd to 3rd decade of life.1,2 The classic histologic findings are the presence of a stratified epithelium consisting of cuboidal to columnar cells with reverse polarization of the basal layer and the presence of ghost cells. A stellate reticulum-like appearance of epithelial cells is also seen. Ghost cells are the most characteristic feature of CCOT and this may represent an abnormal type of keratinization or the coagulative necrosis of the odontogenic epithelium. 3
 CCOT may present alone or in association with other odontogenic tumours.2, 4 Association with an odontoma has been reported in 20% to 24% of cases of CCOT.5 Complex odontoma is a hamartomatous lesion characterized by haphazard arrangement of matrix-producing epithelium, enamel, dentin and cementum-like tissue, in contrast to the more regular structure of a compound odontoma.1
 CCOT associated with odontoma (CCOTaO), in contrast to CCOT alone, has a slight female predominance (2:1), a younger age of presentation (mean 16 years) and a predilection to the maxilla (61.5 %).5 Sidana et al. postulated several possible pathogenesis of CCOTaO including the possibility that CCOT develops secondarily from the epithelium involved in the formation of odontoma or that the odontoma develops secondarily from the epithelium in CCOT.5 Enucleation is the treatment of choice and is curative.
 A close histologic differential diagnosis is an acanthomatous ameloblastoma. Acanthomatous ameloblastoma contains distinct squamous epithelium within nests of ameloblastic epithelium, and ghost cells are absent.
 Very rarely, transformation into its malignant counterpart, ghost cell odontogenic carcinoma (GCOC), has been reported in recurrent cases.6, 7 Infiltrative borders, nuclear atypia and increased mitotic activity indicate this change.6, 7

The expression of NF-κB in Calcifying odonto genic cysts (COCs) and Ghost cell odonto genic carcinomas (GCOCs)

Background: Calcifying odontogenic cysts (COCs) are considered rare odontogenic lesionswith a spectrum of behavioral and clinicopathological features. The rare Ghost cell odontogeniccarcinoma (GCOC) is the malignant counterpart of (COC). The goal of this work was to study theexpression NF-κB in COCs and GCOCs.Methods: NF-κB expression was evaluated in 8 (COCs) and 4 (GCOCs), usingimmunohistochemical method. Immunostaining was evaluated semi-quantitatively, following tothe intensity and extent of staining.Results: B oth cytoplasmic and nuclear and NF-κB immunopositivity were detected in all COCtissues, as well as in GCOC.Conclusion: The expression of NF-κB may represent an important mechanism of tumordevelopment and thus might have a role in the progression of ghost cell lesions.

Calcifying Odontogenic Cyst: Two Histopathological Variants

Calcifying odontogenic cyst (COC) is a developmental cyst lined by ameloblastoma-like epithelium, which contains focal accumulations of ghost cells. COC is one of a group of ghost cell lesions of the jaws, along with dentinogenic ghost cell tumor and ghost cell odontogenic carcinoma, accounting for less than 1% of all odontogenic cysts. Based on its behavior and clinicopathological features, COC has been recently reclassified as a developmental cyst that arises from the dental lamina. We report 2 histopathological variants of COC, which occurred in the maxilla of a woman and in the mandible of a man. One lesion presented as the classical histopathological variant, a unicystic lesion with few layers of epithelial cells and focal accumulations of ghost cells. The second lesion presented as a cyst with extensive ameloblastoma-like proliferation areas along with ghost cells accumulations, an ameloblastomatous variant. The clinical and radiographic aspects of the cases are also discussed.

Calcifying odontogenic cyst, dentinogenic ghost cell tumor, and ghost cell odontogenic carcinoma: A systematic review.

The aim of this study was to integrate the available data published on calcifying odontogenic cyst (COC), dentinogenic ghost cell tumor (DGCT), and ghost cell odontogenic carcinomas (GCOCs) into a comprehensive analysis of their clinicoradiological features, treatment, and recurrence. An electronic search with no publication date restriction was undertaken in October 2017 in the following databases: PubMed, Medline Ovid, Web of Science, and Scopus. Eligibility criteria included publications containing enough clinical, radiological, and histopathological information to confirm a definite diagnosis of these lesions. Data were evaluated descriptively. The literature review indicated a total of 234 publications reporting 367 COCs, 55 DGCTs and 44 GCOCs. These lesions have a predilection for Asian males. COCs mainly affect the mandible and patients in the second decade of life, DGCTs mostly affect the mandible and patients in the fourth decade of life, and GCOCs mostly affect the maxilla and patients in the fifth decade of life. Conservative surgery was the most common therapy for COCs and DGCTs, while radical surgery was most common for GCOCs. This study provides important and interesting data that could help clinicians and surgeons as well as oral and maxillofacial pathologists with the diagnosis and management of these lesions.

A lesion categorized between ghost cell odontogenic carcinoma and dentinogenic ghost cell tumor with CTNNB1 mutation.

Ghost cell odontogenic carcinoma (GCOC) is a rare malignant neoplasm characterized by the presence of ghost cells. It is considered to arise either de novo or from a preexisting benign precursor, calcifying odontogenic cyst (COC), or dentinogenic ghost cell tumor (DGCT). We report a case of a 44-year-old Japanese male with a left maxillary tumor. The patient received treatment to resect the left maxillary cyst 25 years prior; however, the details were uncertain. The tumor was resected with clear margins. Taken together with the results of histological and immunohistochemical examinations, the tumor was categorized between GCOC and DGCT, and we diagnosed the tumor as GCOC suggesting similarity to DGCT. Further, we focused on CTNNB1, which encodes β-catenin and is frequently mutated in COCs. In this tumor, we identified CTNNB1 Ser33Cys, one of the mutations typically found in COCs. This finding suggests that CTNNB1 is a common target for the pathogenesis of tumors accompanied by ghost cells.

Ghost Cell Odontogenic Carcinoma Arising Denovo with Distant Metastasis: A Case Report and Review of Literature

Ghost Cell Odontogenic Carcinoma (GCOC) is a rare malignant odontogenic tumour of epithelial origin accounting about 0.37% to 2.1% of all odontogenic tumours. They are characterized by the presence of ameloblastic islands along with ghost cells representing aberrant keratinization. The aim of this case report is to present a rare case that was diagnosed in a 37-year-old male patient and to describe the behavior of the tumour.

A Case of Ghost Cell Odontogenic Carcinoma in the Maxilla

A Case of Ghost Cell Odontogenic Carcinoma in the Maxilla

Abstract PR02: Integrated genomic analysis of a recurrent ghost cell odontogenic carcinoma

Abstract Introduction: The Personalized OncoGenomics (POG) project launched at the British Columbia Cancer Agency uses genome analyses to support cancer treatment decision making. The POG project enrolls patients with incurable cancers for which standard chemotherapy regimens fail or do not exist. Here we report the first genomic sequence of a ghost cell odontogenic carcinoma (GCOC) patient enrolled in the POG program. GCOC is a very rare cancer of the maxillofacial apparatus and only 35 GCOC cases have been reported in the literature. The etiology of GCOC is largely unknown and genomic profiling of this rare cancer-type has not been previously reported. Methods: We performed whole genome sequencing (WGS; ~100X coverage) and transcriptome sequencing (RNA-seq) of a fresh tumor biopsy sample and WGS (~50X coverage) of DNA purified from peripheral blood. Bioinformatics approaches were used to identify genes with somatic single nucleotide variants (SNVs), copy number variants (CNVs), structural variants (SVs), and expression changes. All variants were integrated to build an individual somatic molecular profile, followed by intensive pathway analysis and literature searches to identify the candidate biological processes that are deregulated. Based on the integration of these results, therapeutic options were explored. Results: The tumor genome was highly aneuploid with extensive regions of loss of heterozygosity. Homozygous deletion of RB1 and heterozygous loss of PTEN, RASSF4 and FHIT tumor suppressors was observed. Oncogenes belonging to the sonic hedgehog pathway (GLI1 and SHH) as well as a variety of other oncogenes including AURKA, AKT1, GSK3B, MYCN also showed gains in copy number. Among the genes with predicted protein altering SNVs were APC, HLF, TWIST1 and UBR5. The only translocation resulting in an expressed RNA product, a reciprocal t(3;18), resulted in a novel fusion involving the TCF4 and PTPRG genes. The predicted fusion product lacks all the functional domains of the PTPRG gene including the phosphatase domain, possibly leading to the loss of tumor suppressor activity. Oncogenes involved in tyrosine kinase signaling (EGFR, KIT, FGFR1), various members of the PI3-kinase-mTOR pathway including PIK3R2, PIK3CA and MYCN, members of the NOTCH signaling pathway (NOTCH1, NOTCH3, JAG1, DTX4, HES2 and HEY1), the hedgehog pathway (PTCH1, GLI1, TWIST1 and TWIST2), and the WNT pathway (WNT4, WNT5A, FZD2, FZD10, DVL3 and GSK3B) were highly expressed in the GCOC sample. Conclusions: This study represents the first integrated genomic and transcriptomic analysis of a GCOC genome. Based on alterations in tyrosine kinase, PI3-kinase-mTOR, hedgehog and NOTCH pathways, inhibitors to these pathways were identified as therapeutic options. This abstract is also presented as Poster 06. Citation Format: Pinaki Bose, Erin Pleasance, Martin Jones, Yaoqing Shen, Carolyn Ch'ng, Caralyn Reisle, Jacqueline E. Schein, Andrew Mungall, Richard Moore, Yussanne Ma, Brandon S. Sheffield, Thomas Thomson, Steven Rasmussen, Christopher Lee, Stephen Yip, Marco A. Marra, Janessa Laskin, Cheryl Ho, Steven J. M. Jones. Integrated genomic analysis of a recurrent ghost cell odontogenic carcinoma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR02.

Abstract 702: BRAF V600E mutation in benign and malignant epithelial odontogenic tumors

Abstract The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82%) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83%) unicystic, 7/9 (78%) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36%) malignant tumours, specifically, 3/8 (38%) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E mutation was less frequent in odontogenic carcinomas than in ameloblastomas. In ameloblastomas, this mutation occurred at similar proportions in cases from the mandible and maxilla, as well as among unicystic, multicystic and desmoplastic variants, suggesting that there is no difference in their molecular pathogenesis. Our findings support the possibility for personalised, molecular targeted therapy for ameloblastomas and ameloblastic carcinomas harbouring the BRAFV600E mutation. Supported by: FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais), CNPq (National Council for Scientific and Technological Development) and CAPES (Coordination for Improvement of Higher Education Personnel), Brazil Citation Format: Marina Goncalves Diniz, Carolina Cavalieri Gomes, Bruna Viana Antonini Guimaraes, Alessandra Pires Duarte, Ricardo Santiago Gomez. BRAF V600E mutation in benign and malignant epithelial odontogenic tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 702. doi:10.1158/1538-7445.AM2015-702

Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours.

The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82 %) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83 %) unicystic, 7/9 (78 %) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36 %) malignant tumours, specifically, 3/8 (38 %) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a secondary genetic event in the ameloblastoma pathogenesis. Our findings support the possibility for personalised, molecular-targeted therapy for ameloblastomas and odontogenic carcinomas harbouring the BRAFV600E mutation.

Malignant transformation of calcifying cystic odontogenic tumour - a review of literature.

Calcifying cystic odontogenic tumour (CCOT) has been classified as an odontogenic tumour. Ghost cell odontogenic carcinoma (GCOC) is the malignant counterpart of CCOT. This paper aims to review the literature regarding malignant transformation of CCOT.A literature search was done via the National Library of Medicine PubMed interface, searching for articles relating to malignant transformation of CCOT. From these articles, references were obtained, and from their references lists, pertinent secondary references were also identified and acquired.After reviewing the literature, we found 26 cases of GCOC which developed from CCOT. Malignant transformation of CCOT was seen more commonly in the maxilla. Histologically, changes such as increased nuclear/cytoplasmic ratio, atypical mitotic figures have been reported after malignant transformation. Immunohistochemical analysis has shown an increased expression of ki-67 and p53 in tumour cells.Malignant transformation of CCOT, although rare, mostly takes place in recurrent and long standing cases.