Calcifying Cystic Odontogenic Tumor Research Articles

Tumor odontogénico quístico calcificante. Reporte clínico patológico de dos casos

El tumor odontogénico quístico calcificante, mejor conocido como quiste odontogénico calcificante es uno de los tumores odontogénicos menos frecuentes de los maxilares y se presenta con una gran diversidad de características clínicas y microscópicas, así como un comportamiento biológico variado. Desde que se identifica a esta lesión como una entidad aislada por Gorlin y cols. en 1962, se ha generado una gran controversia y confusión en relación a su nomenclatura y clasificación, lo que ha provocado diversas propuestas sobre cómo clasificar y cómo llamar a esta lesión. Hasta recientemente, la mayor parte de los investigadores consideraban que el quiste odontogénico calcificante tenía dos entidades básicas: una quística y otra neoplásica, sin embargo en el año 2003 la Organización Mundial de la Salud, basados en investigaciones y clasificaciones previas, establece el término de “Tumor odontogénico quístico calcificante” para la variante quística y lo separa de la variante sólida o neoplásica denominándola “Tumor dentinogénico de células fantasma” como entidades diferentes. En este artículo se reportan dos nuevos casos del tumor odontogénico quístico calcificante (TOQC), así como una revisión de las principales características clínicas, radiológicas y microscópicas de esta lesión.

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.

BONE RECONSTRUCTION SURGERY TO CALCIFY CYSTIC ODONTOGENIC TUMOR: A CASE TREATED BY HYPERBARIC OXYGEN AND BONE RECONSTRUCTION

The calcifying cystic odontogenic tumor (CCOT) is a benign neoplasm that originates from the remnant of the odontogenic epithelium. It is usually of central occurrence, but it may also occur peripherally. The defects resulting from surgical treatments of these tumors cause significant sequels in patients, so restoration of mandibular defects is a challenge for the surgeon. The association between the autogenous graft and the oxygen therapy seems to be a good option in cases of restoration of mandibular defects. This work describes an immediate mandibular restoration of a CCOT associated to a hyperbaric oxygenation of a 63-year-old patient submitted to a segmental resection of the mandible and primary restoration with autogenous, nonvascularized iliac crest excision. Knowing the characteristics of the lesion is fundamental for choosing the best treatment and prognosis. The calcifying cystic odontogenic tumor (CCOT) is a benign neoplasm that originates from the remnant of the odontogenic epithelium. It is usually of central occurrence, but it may also occur peripherally. The defects resulting from surgical treatments of these tumors cause significant sequels in patients, so restoration of mandibular defects is a challenge for the surgeon. The association between the autogenous graft and the oxygen therapy seems to be a good option in cases of restoration of mandibular defects. This work describes an immediate mandibular restoration of a CCOT associated to a hyperbaric oxygenation of a 63-year-old patient submitted to a segmental resection of the mandible and primary restoration with autogenous, nonvascularized iliac crest excision. Knowing the characteristics of the lesion is fundamental for choosing the best treatment and prognosis.

Ameloblastomatous calcifying cystic odontogenic tumor: A review of a rare lesion

Calcifying cystic odontogenic tumor (CCOT) is an uncommon developmental lesion accounting for less than 2% of odontogenic tumors. Because of its diverse histopathology, there has always been confusion about its nature as a cyst or a neoplasm, although it is well known that this lesion often occurs in association with other odontogenic tumors such as complex odontoma and ameloblastoma. It is noted that if CCOT is associated with an ameloblastoma, its behavior and prognosis will be that of an ameloblastoma, not of a CCOT. This article presents a review of all reported cases of ameloblastomatous CCOT in the last 15 years in journals indexed with PubMed.

Calcifying cystic odontogenic tumor of anterior mandible - A case report with series of follow up radiographs

The calcifying odontogenic cyst was first described by Gorlin et al. who were impressed by the presence of numerous ghost cells. Currently, this particular entity is known as calcifying cystic odontogenic tumor (CCOT). Since its recognition, the lesion is seen occurring both peripherally and centrally in the jaws. Its origin, pathogenesis, and histopathological variations have evoked considerable discussions in the past which has resulted in formulation of various classifications. This paper highlights a case of CCOT in the anterior mandible, the characteristic features, treatment and follow-up are discussed, emphasizing on the series of follow-up radiographs.

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

Calcifying cystic odontogenic tumor accompanied by a dentigerous cyst: A case report.

A calcifying cystic odontogenic tumor (CCOT) is a proliferation of odontogenic epithelium and scattered nests of ghost cells and calcifications that may form the lining of a cyst, or present as a solid mass. It was previously described by Gorlin et al in 1962 as a calcifying odontogenic cyst. Dentigerous cysts are developmental odontogenic jaw cysts, commonly manifesting in the second and third decades of life. The present study reports an asymptomatic case in a 13-year-old boy who was referred to the outpatient clinic of the Osaka Dental University Hospital (Osaka, Japan) for additional investigation of an area of radiolucency in the lower right jaw. X-ray demonstrated a unilocular, well-circumscribed, radiolucent lesion in the mandible, which measured 30×20 mm, with radiopaque structures within it. Enucleation of the lesion with tooth extraction was performed, which histopathologically revealed features of a CCOT and a cyst. To the best of our knowledge, the occurrence of such a lesion has not been previously identified. The present study examined the significance of the case with a brief review of the literature.

MAXILLARY CALCIFYING CYSTIC ODONTOGENIC TUMOR ASSOCIATED WITH COMPLEX ODONTOMA: CASE REPORT

The calcifying cystic odontogenic tumor (CCOT) or Gorlin cyst is a rare lesion, described as a benign cystic odontogenic neoplasm. It usually occurs in young adults, between the third and fourth decade of life and presents variable clinical behavior. It may also be associated with odontoma, ameloblastoma or impacted teeth. Recurrences are uncommon and malignant behavior is rare. In this study, it is reported a case of a 35-year-old male patient, presenting with an intraosseous lesion in an occasional panoramic radiograph in the anterior maxilla. Lesion was asymptomatic and the radiograph showed a radiolucent unilocular image, as well as multiple radiopaque structures within the lesion, located between teeth 13 and 15. Teeth were unharmed and were not associated with the lesion. Histopathologic analysis from excisional biopsy pointed to the diagnosis of CCOT associated with Odontoma complex. The patient is currently under active follow-up.

INTERROGATION OF CANCER HOTSPOT MUTATIONS IN CALCIFYING CYSTIC ODONTOGENIC TUMOR

To simultaneously interrogate in calcifying cystic odontogenic tumor (CCOT) about 2,800 COSMIC mutations in a panel of important oncogenes and tumor suppressor genes.

Odontoma-associated calcifying cystic odontogenic tumour: Report of a case

The calcifying cystic odontogenic tumour (CCOT) is an uncommon benign neoplasm of odontogenic origin, which was first described by Gorlin. It has been shown to have extensive diversity in its clinical and histopathological features and its biological behaviour. Most of these cases present with cystic characteristics, but a few are of the solid type.Cystic variant of CCOT associated with odontoma is considered as rare variant. A case of calcifying cystic odontogenic tumour associated with odontoma is reported in an 11-year-old female patient. In this report, the lesion was very large extending from the midline up to the right tuberosity region and impeded the eruption of five permanent teeth. Through this article, the radiographic and histopathological features of this entity are discussed and the literature is reviewed.

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.

Histologic Variants of Calcifying Odontogenic Cyst: A Study of 52 Cases.

This study aimed at evaluating histological features of 52 cases of calcifying odontogenic cyst (COC), which is an uncommon benign odontogenic lesion. The World Health Organization (WHO) classified COC as a neoplasm and used the term calcifying cystic odontogenic tumor (CCOT) for benign cystic type and the dentinogenic ghost cell tumor (DGCT) for the benign solid-type lesions. There is no agreement regarding COC classification. A total of 52 cases of COC were selected and reviewed from the archive of the Pathology Department of Taleghani Educational Hospital, Tehran, Iran. To better understand the pathogenesis of COC, the cases were classified. There were 52 cases (31 males and 21 females). The lesion was found in all age groups, and patients' age from 8 to 61 years. Nineteen cases affected the maxilla, and 33 cases affected the mandible. Except two cases, all were intraosseous lesions. Radiographically, 30 cases showed a unilocular radiolucent area, and 22 cases showed a mixed radiolucent/ radiopaque region. Histopathologically, 43 cases were cystic type and 9 cases were neoplastic. There are two different histopathological entities. In view of these findings, it is very difficult to determine every lesion that has a cystic architecture is truly cystic or is a neoplastic one in nature. It is believed that the solid variants may be neoplastic. A better understanding of the histological type of the lesion can provide a classification across patients. This can help in treatment planning to improve patient outcomes.

Calcifying cystic odontogenic tumour associated with odontoma involving mixed dentition

The calcifying cystic odontogenic tumor (CCOT) is a benign cystic odontogenic tumor relatively uncommon and may be associated with other odontogenic lesions. This manuscript describes a case of CCOT associated with odontoma in a 9-year-old girl, who presented with a slight swelling along with prolonged retention of a maxillary primary central incisor. Radiographic examination showed a unilocular radiolucent lesion containing radiopaque material, associated with an unerupted tooth. Taking into consideration the clinical diagnostic of odontoma, an excisional biopsy was carried out. Microscopic examination established the diagnosis of a CCOT associated with odontoma. The association of these lesions is rare in individuals in the first decade of life, particularly involving mixed dentition, as outlined in this case. The patient remains under care with no clinical signs of recurrence.

Keratocystic odontogenic tumor overexpresses invadopodia-related proteins, suggesting invadopodia formation

Keratocystic odontogenic tumor (KOT) is an odontogenic neoplasm that shows aggressive clinical behavior and local invasiveness. Invadopodia are actin-rich cellular protrusions exhibiting proteolytic pericellular activity, thereby inducing focal invasion in neoplastic cells and increasing neoplasms aggressiveness. Thus, this study aimed to evaluate immunoexpression of invadopodia-related proteins, cortactin, MT1-MMP, Tks4, and Tks5, in KOT. Immunohistochemistry of 16 cases of KOT, eight cases of calcifying cystic odontogenic tumor (CCOT), and eight samples of the oral mucosa (OM) was carried out to assess the expression of the above described invadopodia-related proteins in the basal and suprabasal layer. KOT samples showed higher and significant immunoexpression of cortactin, MT1-MMP, TKs4, and TKs5 compared with the CCOT and OM samples. Significant expression of all these proteins was observed in the basal layer compared with the suprabasal layer in KOT. Overexpression of cortactin, MT1-MMP, TKs4, and TKs5 was observed in KOT compared with samples of CCOT and OM. These proteins were also overexpressed in the basal over the suprabasal layer of KOT samples. Taken together, these results suggest the participation of invadopodia-related proteins on the pathogenesis of this lesion.

Asymptomatic calcifying cystic odontogenic tumor presenting as a random radiographic finding

Calcifying cystic odontogenic tumor (CCOT), a rare odontogenic lesion, usually appears as radiolucency with radiopacities. This characteristic finding may not always be evident depending on the lesion stage, growth, and histopathological features. An asymptomatic case of CCOT alongside an unerupted third molar that was discovered randomly after a routine panoramic radiograph is presented in a 28-year-old male patient. The imaging examination by cone beam computed tomography revealed a unilocular corticated radiolucency in close association with the buccal aspect of a fully impacted mandibular third molar that extended to the apical third of the tooth. The roots appeared outside the lesion and there was no evidence of resorption or jaw bone erosion. Based on the imaging findings, the provisional clinical diagnosis was dentigerous cyst. After the surgical removal of the cystic lesion, which had adhered in the cemento-enamel junction of the third molar, the histopathological examination showed a CCOT. Unerupted third molars should be investigated radiographically even in the absence of clinical signs for the early diagnosis and management of the various odontogenic cysts and tumors.

Immunohistochemical evaluation of inducible nitric oxide synthase (iNOS) expression in the dental follicle, follicular cyst, and calcifying cystic odontogenic tumor

ObjectiveThe calcifying cystic odontogenic tumor (CCOT) is a benign cystic neoplasm with a variety of histopathological and clinical features in comparison with the follicular cyst. iNOS is an enzyme that produces free radicals and is a mediator regulator of the inflammatory response. It has been implicated in tumorigenesis as well. The aim of this study was to compare iNOS expression in the dental follicle and two odontogenic lesions with different aggressive behaviors. MethodsIn this cross-sectional study, 44 paraffin blocks were selected from the dental follicle, follicular cyst, and CCOT, and immunohistochemical staining was done by iNOS. The percentage and intensity of staining (total score) were calculated in the cytoplasm of the epithelial cells. ResultsThe highest total score of iNOS staining was found in the cytoplasm of the epithelial cells of CCOT when compared to the follicular cyst and dental follicle (p=0.000). There was a significant difference in the final score between the follicular cyst and dental follicle (p=0.001). DiscussionThe overexpression of iNOS in the CCOTs plays a role in its pathogenesis and iNOS, because of producing free radicals and damaging the oral tissue, may contribute to more aggressive behaviors of CCOT.

Early Detection of a Calcifying Cystic Odontogenic Tumor associated with Odontoma

A 15-year-old male patient was referred for diagnosis and treatment of a radiographic lesion located in the anterior region of the maxilla. Clinically, the patient presented a prolonged retention of the element 63 and absence of the element 23. No swelling around the alveolar ridge was observed. The radiographic findings were characterized by few tooth-like radiopaque structures surrounded by a radiolucent halo around the impacted element 23. The clinical hypothesis was stablished as dentigerous cyst associated with compound odontoma. The excisional biopsy was performed keeping the impacted tooth in place, to which an orthodontic bracket was bond for posterior traction. The surgical piece was taken to histopathological examination and the final diagnosis was calcifying cystic odontogenic tumor (CCOT) associated with compound odontoma. The calcifying cystic odontogenic tumor (CCOT) is a rare benign neoplastic lesion that represents less than 2% of all cysts and odontogenic tumors; it is usually found at the canine region and is associated with odontoma. Knowledge on the lesion characteristics, a detailed clinical exam, and complementary exams are essential to a differential diagnosis aiming to provide appropriate treatment for the patient, which currently consists of complete enucleation, with good prognosis. The 12-month follow-up shows an injury-free patient

Calcifying cystic odontogenic tumor associated with unicystic ameloblastoma: Report of a rare hybrid odontogenic tumor

A hybrid odontogenic tumor comprising two distinct lesions is extremely rare. In this paper, we report one such case of hybrid odontogenic tumor composed of calcifying cystic odontogenic tumor and unicystic ameloblastoma in the left maxillary anterior region of a 30-year-old Indian male. Calcifying cystic odontogenic tumor (CCOT) is a benign cystic neoplasm of odontogenic origin, which involves association of a cyst (calcifying odontogenic cyst) with an odontogenic tumor, a finding which is a rare event in other types of odontogenic cysts or tumors. CCOT associated with unicystic ameloblastoma is a rare entity with very few cases being documented in literature. Preoperative diagnosis of such hybrid lesions can be difficult or sometimes impossible because it shares significant clinical and radiographic similarities with odontogenic cysts and tumors.

Immunohistochemical expression of WNT5A and MMPs in odontogenic epithelial tumors and cysts

ObjectiveThe aim of this study was compare the expression of WNT5A and MMP2, 7 and 20, in frequent benign odontogenic tumors and odontogenic cysts, since these lesions have a different biological behavior. Materials and methodsEighty-one paraffin-embedded specimens of odontogenic tumors, including ameloblastoma and keratocystic odontogenic tumor, and thirty-two odontogenic cysts were used for immunohistochemical analysis. ResultsThe expression of WNT5A in odontogenic tumors and inflammatory cyst was higher than in developmental odontogenic cyst. There was no statistical difference (p<0.05) in the expression of WNT5A when comparing the analyzed tumors. The expression of MMP7 was lower in RC with a statistical difference when compared with all tumors and cysts. Statistical differences also occurred when comparing glandular odontogenic cyst (GOC) to keratocyst odontogenic tumor (KOT) and calcifying cystic odontogenic tumor (CCOT). MMP20 expression was higher in ameloblastoma when compared to adenomatoid odontogenic tumor (AOT), DC and GOC. The expression of MMP20 was lower in CCOT when compared to all tumors and cysts. ConclusionsThe expression of WNT5A in a group of odontogenic lesions suggests the participation of a non-canonical WNT signaling pathway in the progression and maintenance of these lesions. These molecules are possibly involved in the biological differences between odontogenic tumors and cysts. Considering previous studies, WNT5A may help promote the calcification seen in AOT, CCOT and CEOT by activating MMP7.

Peripheral Calcifying Cystic Odontogenic Tumor: Report of a Case and Evidence Against its Neoplastic Classification

The most recent World Health Organization (WHO) classification of odontogenic tumors published in Pathology and Genetics. Head and Neck Tumors in 2005 classifies the ghost cell lesions as neoplasms because there is a solid, non-cystic variant. However, most ghost cell lesions are cystic and the WHO offered no scientific evidence for reclassifying the cystic lesions as neoplasms. Accordingly, the reclassification has remained controversial. The most common lesion that contains ghost cells is the calcifying cystic odontogenic tumor (CCOT) or calcifying odontogenic cyst (COC), which is characterized by ameloblastic epithelium and numerous ghost cells. Approximately 20 percent of these are extraosseous. Even though the WHO defines this lesion as a neoplasm, it shows little neoplastic potential and has a low recurrence rate of around 5% with conservative enucleation or local excisional treatment. Does this classification truly describe lesion behavior and does it lead to appropriate treatment?