Prevalence of developmental odontogenic cysts in children and adolescents with emphasis on dentigerous cyst and odontogenic keratocyst (keratocystic odontogenic tumor)

Objective. To investigate the incidence and prevalence of developmental odontogenic cysts in children and adolescents and compare the features of the two most common types, dentigerous cyst and keratocystic odontogenic tumor (KCOT). Study design. A retrospective review in a series of 369 patients with all histological diagnoses of developmental odontogenic cysts in children (≤12 years) and adolescents (13–18 years) was conducted. Results. Among these, 361 (97.8%) patients were diagnosed as dentigerous cyst (n = 281) and KCOT (n = 80), with the male-to-female ratios of dentigerous cyst and KCOT both being 2:1. The average age of the patients with KCOT was older than that of those with dentigerous cyst (14.7 years vs 11.8 years, p < 0.001). Dentigerous cyst (59.1%) was more common in children, but KCOT (78.8%) was more common in adolescents (p < 0.001). Dentigerous cyst (57.6%) predominantly located on the maxilla, but KCOT (60.3%) predominantly located on the mandible (p = 0.010). Conclusions. Adolescent patients with lesions located on the mandible would favor KCOT over dentigerous cyst. This study aids in better knowledge of the prevalence of developmental odontogenic cysts in a large pediatric population, and shows that a well-supported early diagnosis is indispensable for a more adequate treatment.     

Alterations of FHIT and P53 genes in keratocystic odontogenic tumor, dentigerous and radicular cyst

Background:  The purpose of this study was to determine fragile histidine triad (FHIT) and p53 protein expression, and to analyze FHIT and p53 gene status in keratocystic odontogenic tumor (KOT), dentigerous cysts (DC) and radicular cysts (RC).
Methods:  The methods used were immunohistochemistry and molecular genetic methods including loss of heterozygosity (LOH) and gene sequencing.
Results:  FHIT protein expression was different among groups. Aberrant expression was the highest in KOT, then in RC and DC. p53 protein expression was different among groups. LOH in paraffin-embedded specimens was detected in 22.6% and 12.9% for FHIT and p53 respectively. Mutation of p53 gene at codon 237 was observed in only two specimens (one KOT and one DC). Of the six frozen specimens, three exhibited FHIT gene LOH (two RC and one KOT). KOT showed loss of exons 6–7 at FHIT locus and mutation at codon 237 at p53 locus, but this could be a chance result.
Conclusion:  Aberrations of FHIT and p53 genes/proteins could be considered markers responsible for the development of odontogenic lesions.     

A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma

OBJECTIVES: The aim of the present study was to compare the proliferation index of the epithelial cells between odontogenic keratocysts (OKC), orthokeratinized odontogenic cysts (OOC), dentigerous cysts (DC), and ameloblastomas. MATERIALS AND METHODS: The proliferation index, employing a novel cell proliferation marker IPO-38, was studied by the immunohistochemical technique in 10 OKC, seven OOC, eight DC and 10 ameloblastomas. RESULTS: The ameloblastoma had no higher labeling index (LI) of IPO-38 than the OKC (P = 0.910) but had higher LI than the OOC (P = 0.001) and DC (P = 0.000); the OKC had higher LI than the OOC (P = 0.002) and DC (P = 0.000); and the OOC had higher LI than the DC (P = 0.011). IPO-38-positive cells in the OKC and OOC were located principally in the suprabasal cell layers while the ameloblastoma were found in the peripheral portion in particularly, the follicular and plexiform types. CONCLUSION: These findings support previous studies that the proliferation indices are useful in predicting the different biological behavior of the odontogenic lesions and the OKC should be regarded as a benign tumor rather than simply an odontogenic cyst.     

Significance of podoplanin expression in keratocystic odontogenic tumor

J Oral Pathol Med (2010) 39 : 110–114
Background:  The most important clinical features of the keratocystic odontogenic tumor (KCOT) are its potential for locally destructive behavior, a tendency to recur, and its origin in the odontogenic epithelium. The clinical features of KCOT are similar to those of ameloblastoma (AM). Histologically, KCOT is distinguished from jaw cyst with keratinization (orthokeratinized odontogenic cyst; OOC). However, current scientifically based clinical parameters cannot predict any potential for neoplastic behavior, or aggressive and localized invasiveness, in patients with KCOT. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in AM. The purpose of this study was to determine the usefulness of podoplanin for reclassification of the odontogenic keratocyst (OKC) from cyst to tumor status.
Methods:  Paraffin-embedded tissue specimens of 57 OKCs (46 KCOTs and 11 OOCs) and 15 dentigerous cysts (DCs) were immunohistochemically examined using antibody against podoplanin.
Results:  Immunohistochemical reactivity for podoplanin was detected in the cell membrane and cytoplasm of most of the basal and suprabasal layer, areas of budding basal cell proliferation, epithelial nests and peripheral cells of daughter cysts in the stromal connective tissue in KCOTs. In the case of OOC and DC, only cases associated with inflammation were positive for podoplanin.
Conclusion:  Podoplanin is strongly expressed in KCOTs in comparison with OOCs. The pattern of staining for podoplanin in KCOT could be related to its neoplastic nature, and suggests a role of the protein in tumor invasiveness.     

LINE‐1 methylation difference between ameloblastoma and keratocystic odontogenic tumor

Oral Diseases (2010) 16 , 286–291 Objective: Global hypomethylation is a common epigenetic event in cancer. Keratocystic odontogenic tumor (KCOT) and ameloblastoma are different tumors but posses the same tissue in origin. Here, we investigated long interspersed nuclear element‐1 (LINE‐1 or L1) methylation status between ameloblastoma and KCOT. Materials and methods: We studied the methylation levels of the long interspersed nucleotide element‐1 (LINE‐1) in ameloblastoma and KCOT. After collecting ameloblastoma cells and epithelium lining cells of KCOT by laser capture microdissection from paraffin embedded tissue, combined bisulfite restriction analysis of LINE‐1 (COBRALINE‐1) was performed to measure LINE‐1 methylation levels. Results: The LINE‐1 methylation level in KCOT (53.16 ± 12.03%) was higher than that in ameloblastoma (36.90 ± 16.52%), with a statistical significance of P = 0.001. The ranges of LINE‐1 methylation of both lesions were not associated with either age or sex. Conclusion: We found LINE‐1 hypomethylation levels between ameloblastoma and KCOT are different. Therefore, global methylations between these tumors are processed differently.     

Metallothionein in the radicular,dentigerous, orthokeratinized odontogenic cysts and in keratocystic odontogenic tumor

J Oral Pathol Med (2011) 40 : 270–276 Background: Metallothionein (MT) is a protein correlated with cellular differentiation and proliferation, as well as with the inhibition of apoptosis. The aims were to report and to compare the MT expression in odontogenic cysts and keratocystic odontogenic tumor (KOT); to correlate the MT with cellular proliferation; and to evaluate the influence of the inflammation in MT. Methods: Nine cases of radicular cyst (RC), nine dentigerous cyst (DC), four orthokeratinized odontogenic cyst (OOC), and eight KOT were submitted to immunohistochemistry using anti‐MT and anti‐Ki‐67. Indexes of MT (IMT) and Ki‐67 (IK) were obtained. Lesions were grouped according to inflammation: mild‐to‐moderate (group A) and intense (group B). Results: IMT proved to be highest in RC (91%), followed by DC (89%), KOT (78%), and OOC (63%). IMT was inversely correlated with IK in KOT, and OCC, but was positively correlated with RC and DC. No differences in IMT and in IK could be observed between groups A and B. Conclusions: The higher IMT found in RC and DC compared to OCC and KOT, as well as the differences between the last ones, is possibly correlated with their different histopathological features and clinical behavior. In RC and DC, MT may play a role in cellular proliferation. However, it seems that MT is either less or is not related to proliferation in OOC and in KOT. Moreover, inflammation does not seem to alter IMT and IK.     

Co-expression of Ki-67 and p53 protein in ameloblastoma and keratocystic odontogenic tumor

Abstract

Objectives. The purpose of this study was to evaluate the cell proliferation and p53 protein expression in ameloblastomas (ABs), keratocystic odontogenic tumor (KCOT) and dentigerous cyst (DC). Method. The immunohistochemistry were carried out for Ki-67 and p53 protein expression by using MIB-1 clone and DO-7 clone, respectively, in ABs (n = 23), KCOT (n = 32), DC (n = 30), normal oral mucosa (NOM) (n = 12) and fetal oral mucosa (FOM) (n = 10). Results. Both the Ki-67 LI Labeling index (LI) and p53 LI was significantly higher in ABs than KCOT, DC, NOM and FOM. The Ki-67 LI and p53 LI was significantly higher in KCOT as compared to DC. Ki-67 LI and p53 LI was observed in descending order in ABs, KOCT, FOM, NOM and DC. There was significant correlation between Ki-67 expression and p53 expression in ABs, KCOT, DC and NOM. The densely stained p53 positive cells were noted higher in ABs than KCOT. The very few densely p53 positive cells were noted in DC, NOM and FOM. Conclusion. The results suggest that the p53 protein expression does not necessarily imply an association with malignant disease and/or p53 gene mutation, but a tendency to be expressed in an increasing quantitative and qualitative manner, as the biologic behavior of odontogenic cyst or tumors becomes more aggressive. p53 over-expression may promote cell proliferation in odontogenic lesions. Thus, it can be stipulated that Ki-67 and p53 protein expression can be used as a prognostic marker in odontogenic lesions.     

Ameloblastoma ex calcifying odontogenic cyst (dentinogenic ghost cell tumor)

Calcifying odontogenic cyst (COC) has shown to be of extensive diversity in its clinical and histopathological features, as well as in its biological behavior. In this report, a rare case is described of ameloblastoma ex COC (dentinogenic ghost cell tumor) and the relevant literature is briefly reviewed.     

Ameloblastoma, calcifying epithelial odontogenic tumor, and glandular odontogenic cyst show a distinctive immunophenotype with some myoepithelial antigen expression

Background:  Odontogenic neoplasms have some morphologic overlap with salivary gland neoplasms, many of which show myoepithelial differentiation. In the 1980s, an ultrastructural study identified a population of myoepithelial-like cells in calcifying epithelial odontogenic tumor. Myoepithelial derived tumors have since been shown to have distinct immunohistochemical profiles.
Methods:  We examined a series of odontogenic neoplasms, including 11 ameloblastomas, four calcifying epithelial odontogenic tumors, five glandular odontogenic cysts (GOCs), and five keratocystic odontogenic tumors with a panel of myoepithelial-associated immunohistochemical stains. We also assessed representative control examples of oral mucosa, odontogenic rests, and dentigerous cysts.
Results:  All of the neoplastic and non-neoplastic oral epithelium-derived entities share a p63-positive, high molecular weight cytokeratin (CK5/6)-positive immunophenotype. Calponin reactivity was at least focally present in two of four calcifying epithelial odontogenic tumors, three of five GOCs, and 10 of 11 ameloblastomas; the sole completely non-reactive ameloblastoma represents a lung metastasis. One case of calcifying epithelial odontogenic tumor was focally positive for glial fibrillary acidic protein. However, other more definitive markers of myoepithelial differentiation, including S-100 and smooth muscle actin, were negative. Two of three calcifying epithelial odontogenic tumors and five of five GOCs were also positive for a low molecular weight cytokeratin (CK7).
Conclusions:  Ameloblastomas, GOCs, and calcifying epithelial odontogenic tumors show a distinctive immunophenotype which overlaps with that of myoepithelial-derived salivary gland neoplasms but does not provide definitive support for myoepithelial differentiation.     

Comparison of angiogenesis in keratocystic odontogenic tumours, dentigerous cysts and ameloblastomas

Objective:  The aim of the present study was to evaluate and compare angiogenesis in keratocystic odontogenic tumours, dentigerous cysts (DCs) and ameloblasomas using monoclonal antibody against CD34.
Materials and methods:  Microvessel density was assessed in a total of 53 cases including 20 keratocystic odontogenic tumours, 13 DCs and 20 ameloblastomas (14 solid and six unicystic variants). Microvessel density was expressed as the mean number of microvessels per high-power-field.
Results:  Statistically significant differences in mean microvessel density were observed between keratocystic odontogenic tumours, DCs and solid ameloblastomas ( P  < 0.001). Mean microvessel density was significantly higher in solid ameloblastomas compared with both keratocystic odontogenic tumours and DCs; and was also significantly higher in keratocystic odontogenic tumours than in DCs.
Conclusion:  Within the limitations of the present study, it can be suggested that angiogenesis may be one of the mechanisms possibly contributing to the different biological behaviours of keratocystic odontogenic tumours, DCs and solid ameloblastomas.     

The differential expression pattern of BMP-4 between the dentigerous cyst and the odontogenic keratocyst

BACKGROUND: Bone morphogenic protein-4 (BMP-4) is widely expressed in oral cavity and involved in tooth morphogenesis, cellular differentiation and proliferation. The purpose of this study was to compare the difference in expression pattern of BMP-4 in odontogenic keratocysts (OKC) and dentigerous cysts (DC). METHODS: We evaluated 77 cysts, OKC (n = 34) or DC (n = 43). The average age of patients with OKC was 29.5 +/- 14.4 and that of patients with DC was 36.1 +/- 19.4. The male to female ratio was 20:14 for OKC and 27:16 for DC. Ten cases of OKC were recurrences. Expression of BMP-4 was determined by immunohistochemistry and in situ hybridization. RESULTS: The intensity scales were (-) for invisible or trace staining, (+) for visible staining, and (++) for dense, strong staining. OKCs exhibited the following staining patterns: the epithelium in 15/34 specimens and the mesenchymal cells in 17/34 specimens showed (++) stain. In contrast, the staining pattern of DC was (-) for epithelium in 37/43 specimens. The mesenchymal cells showed (-) degree staining in 30/43 specimens. The difference between the groups studied was significant (P < 0.001 in epithelium and mesenchymal cells). When recurrent and non-recurrent OKC were compared BMP-4 was expressed more intensely in the recurrent cases (P = 0.036 in epithelium). The difference in BMP-4 expression in mesenchymal cells was not significant. In situ hybridization demonstrated positive mRNA probes to BMP-4 were localized in epithelium and mesenchymal cells of OKCs and DCs. CONCLUSIONS: BMP-4 was expressed more intensely in OKC when compared with DC, and was more intensely expressed in recurrent cases.     

Age-standardized incidence rates of ameloblastoma and dentigerous cyst on the Witwatersrand, South Africa

Although a great deal is known about the incidence of cancer, including oral cancer, no such study has been done on odontogenic tumors and jaw cysts. There are therefore no standardized data which would allow for comparative incidences in different countries and between different groups. In the present study, cases of ameloblastomas and dentigerous cysts derived from the records of all the hospital pathology departments and private pathology practices on the Witwatersrand, were recorded for the 10-year period 1965--1974. The population at risk (1970 census) was 974,390 Whites and 1,567,280 Blacks. The annual incidence rates, standardized against the standard world population, for ameloblastomas per million population are 1.96, 1.20, 0.18 and 0.44 for Black males, females and White males, females, respectively. The equivalent four figures for dentigerous cysts are 1.18, 1.22, 9.92 and 7.26. These figures show that ameloblastoma is very much more common in Blacks than Whites in the population at risk. Conversely, dentigerous cysts are much more common in Whites. This makes it unlikely that dentigerous cysts predispose to ameloblastoma formation. These epidemiologic observations give rise to speculation as to whether some component of the South African Black diet or other environmental substance might possibly be an etiologic factor in ameloblastoma.     

Tumor angiogenesis in keratocystic odontogenic tumor assessed by using CD‐105 antigen

J Oral Pathol Med (2011) 40 : 263–269 Background: The purpose of this study was to assess and compare angiogenesis with proliferative activity in Keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC) by using monoclonal mouse anti‐human antibody against CD105 (endoglin). Material and Methods: Angiogenesis was assessed in 38 KCOT, 27 DCs and 19 Normal Oral Mucosa (NOM) by measuring the Mean Vascular Density (MVD), Total Vascular Area (TVA) and Mean Vascular Area (MVA). Cell proliferation was assessed by obtaining Ki‐67 Labeling Index (Ki‐67LI) in all the groups. Results: Statistically significant difference was observed in MVD, TVA, MVA and Ki‐67 LI between the KCOT, DC and NOM (P = 0.000). The MVD, TVA, MVA and Ki‐67 LI were significantly higher in KCOT than in DC and NOM (P = 0.000). The Ki‐67 LI was significantly higher in NOM than in DC (P = 0.000). MVD (P = 0.032) and TVA (P = 0.038) were significantly higher in NOM than in DC. There was significant positive correlation between Ki‐67 LI and MVD, Ki‐67 and TVA and Ki‐67 and MVA. Conclusion: The result suggests that CD105 (endoglin) is strongly expressed in microvessels of KCOT compared with that in Dentigerous cyst and Normal oral mucosa. Thus, it suggests that angiogenesis may be associated with locally aggressive biological behavior of KCOT. These findings further stress on the hypothesis that the stroma of KCOT could be regarded not just as a structural support of the cyst wall, but as playing a part in the neoplastic behavior of cyst.     

Histopathologic study of epithelial components in the connective tissue wall of unilocular type of calcifying odontogenic cyst

Histopathologic study of satellite cysts and odontogenic epithelial islands in connective tissue wall of unilocular type of calcifying odontogenic cyst (COC) was made. The material was 13 cases consisting of 3 simple unicystic COCs, 9 odontome producing COCs and 1 ameloblastomatous proliferating COC. Satellite cysts were found in 6 cases, and were histologically classified into following types: simple cystic, odontome producing and ameloblastomatous. Histologic types of satellite cysts did not coincide with those of main cystic lesions in some cases. Odontogenic epithelial islands with or without proliferating feature were found in 9 cases, and were found in all cases with satellite cysts. Melanin and melanocytes were seen in an ameloblastomatous satellite cysts of 1 of 3 pigmented COCs.     

Primordial odontogenic tumor: Subepithelial expression of Syndecan‐1 and Ki‐67 suggests origin during early odontogenesis

Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan‐1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell‐to‐cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation. Ki‐67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan‐1 and Ki‐67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan‐1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan‐1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla.     

Surgical management of dentigerous cyst and keratocystic odontogenic tumor in children: a conservative approach and 7-year follow-up

Dentigerous cyst (DC) is one of the most common odontogenic cysts of the jaws and rarely recurs. On the other hand, keratocystic odontogenic tumor (KCOT), formerly known as odontogenic keratocyst (OKC), is considered a benign unicystic or multicystic intraosseous neoplasm and one of the most aggressive odontogenic lesions presenting relatively high recurrence rate and a tendency to invade adjacent tissue. Two cases of these odontogenic lesions occurring in children are presented. They were very similar in clinical and radiographic characteristics, and both were treated by marsupialization. The treatment was chosen in order to preserve the associated permanent teeth with complementary orthodontic treatment to direct eruption of the associated permanent teeth. At 7-years of follow-up, none of the cases showed recurrence.