Familial odontogenic keratocysts. Report of 3 cases and review of Japanese dental literature

Familial odontogenic keratocysts are described in this report. The Case 1 patient, who has 3 sisters, developed odontogenic keratocysts. The 2 younger sisters (Cases 2 and 3) also had odontogenic keratocysts, although the elder sister did not have any odontogenic cysts. The father of the patients had a history of removal of a jaw cyst, and the mother was found later to have malignant ameloblastoma. Besides the odontogenic keratocysts, the Case 1 patient had basal cell nevus, prominent frontal process, and ocular hypertelorism; the Case 2 patient had prominent frontal process; the Case 3 patient had prominent frontal process, ocular hypertelorism, and squint. All 3 sisters are suspected of being patients with the basal cell nevus syndrome. The Japanese dental literature concerning the basal cell nevus syndrome is reviewed.     

Discrimination of parakeratinised odontogenic keratocysts from other odontogenic and non-odontogenic cyst types by expression of a 38kd cell-surface glycoprotein

We have identified strong expression of a 38-kD cell surface glycoprotein (gp38), a marker of basal cell carcinomas (BCCs), in basal and suprabasal epithelial cell membranes of parakeratinised odontogenic keratocysts. In contrast, orthokeratinised cysts and most other odontogenic cyst types, ameloblastomas, normal stratified oral epithelium, cell rests of Malassez and glands of Serres, all proved negative. To our knowledge this is the first histochemical marker to distinguish between these major cyst types. It has obvious uses in the diagnosis of inflamed keratocysts and the separation of ameloblastomas from BCCs and may find a role in studies of the developmental biology of other odontogenic structures.     

The Prevalence of EBV and KSHV in Odontogenic Lesions

ObjectivesOdontogenic lesions evolve as a result of altered dental development. This study aimed to evaluate the prevalence and the coinfection of Epstein-Barr virus (EBV) and Kaposi sarcoma–associated herpesvirus (KSHV) in radicular cysts, dentigerous cysts, odontogenic keratocysts, and ameloblastomas.MethodsPolymerase chain reaction (PCR) was used to analyse 66 cases of odontogenic lesions for the presence of EBV-DNA and KSHV-DNA. These lesions were 15 radicular cysts, 16 dentigerous cysts, 18 odontogenic keratocysts, and 17 ameloblastomas.ResultsEBV-DNA was detected in 24 (36.4%) of the studied samples as follows: 6 samples (40.0%) of radicular cysts, 4 (25.0%) of dentigerous cysts, 10 (55.6 %) of odontogenic keratocysts, and 4 (23.5%) of ameloblastomas (P = .168). KSHV-DNA was found in 16 (24.2%) of the studied samples as follows: 1 sample (6.7%) of radicular cysts, 6 (37.5%) of dentigerous cysts, 8 (44.4 %) of odontogenic keratocysts, and 1 (5.9%) of ameloblastomas (P = .001). Additionally, EBV and KSHV were positively correlated in all studied samples (P = .002).ConclusionsBoth EBV and KSHV are found in odontogenic cysts and ameloblastomas. KSHV and EBV are more prevalent in odontogenic keratocysts than in other studied odontogenic lesions. Further, there is a high prevalence of EBV and KSHV coinfection in odontogenic cysts and ameloblastomas.     

A comparative histological study of odontogenic keratocysts in basal cell naevus syndrome and control patients

164 odontogenic keratocysts from 60 patients with the basal cell naevus syndrome were compared with a similar number of single keratocysts matched for age and site. Significant differences between the two groups were found in the numbers of satellite cysts, solid islands of epithelial proliferation and odontogenic rests within the capsule, and in the numbers of mitotic figures in the epithelium lining the main cavity. An index of activity derived from these parameters suggests a greater growth potential in syndrome cysts; in addition, the patterns of association of the features support the theory that the odontogenic rests give rise to satellite cysts.     

A comparative histological study of odontogenic keratocysts in basal cell naevus syndrome and control patients

164 odontogenic keratocysts from 60 patients with the basal cell naevus syndrome were compared with a similar number of single keratocysts matched for age and site. Significant differences between the two groups were found in the numbers of satellite cysts, solid islands of epithelial proliferation and odontogenic rests within the capsule, and in the numbers of mitotic figures in the epithelium lining the main cavity. An index of activity derived from these parameters suggests a greater growth potential in syndrome cysts; in addition, the patterns of association of the features support the theory that the odontogenic rests give rise to satellite cysts.     

Immunohistochemical analysis of the biological potential of odontogenic keratocysts

BACKGROUND: The aim of this study was to analyse the usefulness of detecting important apoptosis and proliferation markers in assessing the biological potential of odontogenic keratocysts (OKC) and thus selecting the optimal diagnostic algorithm for these lesions. METHODS: Indirect immunohistochemistry and relevant statistical methods were used for analysis of formalin-fixed and paraffin-embedded samples from 98 patients. RESULTS: Nevoid basal cell carcinoma syndrome (NBCCS) keratocysts were characterized by higher expression of Bcl-2, p27Kip1 and c-erbB-2 as well as by lower proliferative activity measured by Ki-67 in basal cell epithelium and by a lower inflammatory response in comparison with sporadic keratocysts. Dentigerous, radicular and non-specified odontogenic cysts differed from both NBCCS and sporadic keratocysts in a wide spectrum of apoptosis and/or cell cycle-related protein expressions, higher proliferation in the basal cell layer, and vice versa, lower proliferation in the suprabasal cell layer. CONCLUSIONS: The NBCCS keratocysts have a different immunophenotype from sporadic keratocysts and both types are distinguishable from dentigerous, radicular and non-specified odontogenic cysts. These findings confirm the separate biological potential of these lesions and the results of the immunohistochemical analysis have diagnostic and prognostic implications.     

The odontogenic keratocyst. A clinicopathologic study of 312 cases. Part I. Clinical features.

An analysis was made of the clinical features of 312 acceptable cases of odontogenic keratocysts from the files of the Department of Oral Pathology, Indiana University School of Dentistry. A total of 5.1 per cent of the keratocysts were from patients with the basal-cell nevus syndrome and 5.8 per cent were from patients with multiple keratocysts but with no other features of the syndrome. There was a wide age range, with a peak incidence in the second and third decades of life. The mandible: maxilla ratio was 2:1, with the mandibular third molar area and ramus being the most common sites. Dentigerous cyst was the most frequent clinical as well as histologic diagnosis for the majority of the keratocysts in this study. The primordial cyst comprised the greatest percentage of keratocysts (44.4 per cent). A total of 50.3 per cent of the patients were symptomatic before seeking treatment, the most common finding being intraoral drainage and swelling. Their radiographic appearance was quite variable, although they frequently resembled ameloblastoma. These cysts may be very aggressive clinically. They have a relatively high recurrence rate, as previously reported in the literature, in comparison with other types of odontogenic cyst. The findings in this study support the theory that the histologic appearance of an odontogenic keratocyst may be assumed by any of the odontogenic or nonodontogenic cysts.     

Recurrence of keratocysts. A long-term follow-up study

The aim of the study was to investigate the recurrence rate of keratocysts based on a material with a follow-up of at least 5 years, and to evaluate the relationship between different features of these cysts and their recurrence. It was found that of 75 keratocysts with follow-up times ranging from 5 to 17 years (mean 8.3), 32 (43%) recurred. The cumulative recurrence rate of the 67 annually examined cysts increased from 3% after the 1st year following the operation to 37% after the 3rd year. Thereafter, no new recurrences were noted. Recurrence of keratocysts in patients with basal cell nevus syndrome occurred more frequently than that of patients without the syndrome. Keratocysts enucleated in one piece recurred significantly less often than cysts enucleated in several pieces. The recurrence rate of keratocysts with a clinically observable infection, with fistula or with a perforated bony wall was higher than that of keratocysts without these features. Recurrence was also found more frequently in cysts with multilocular radiographic appearance than in unilocular cysts. The size or the location of the keratocysts did not have an influence on the recurrence rate.     

Calretinin expression in odontogenic cysts

Calretinin is a calcium-binding protein with a possible role as a calcium buffer, calcium-sensor, or regulator of apoptosis. Calretinin is expressed in neural tissue, is a specific marker of mesothelial cells, and has been demonstrated in the odontogenic epithelium during odontogenesis in rat molar tooth germs. Moreover, it has been found to be expressed in a high proportion of solid, unicystic, and multicystic ameloblastomas, whereas, on the contrary, no positive staining has been found in odontogenic keratocysts, residual cysts, and dentigerous cysts. The purpose of this study was to evaluate calretinin expression in radicular cysts, follicular cysts, orthokeratinized keratocysts, and parakeratinized keratocysts. A total of 70 odontogenic cysts, 24 radicular cysts, 24 follicular cysts, and 22 odontogenic keratocysts (10 orthokeratinized keratocysts, 12 parakeratinized keratocysts) were evaluated. All the radicular cysts, follicular cysts, and orthokeratinized keratocysts were negative. However in 8 of 12 parakeratinized keratocysts, there was a positivity to calretinin in the parabasal-intermediate layers of the cyst epithelium. This positivity to calretinin in the parabasal layers in parakeratinized keratocysts, similar to that found for other markers like PCNA and p53, could point to an abnormal control of the cell cycle and could help to explain the differences in the clinical and pathologic behavior of odontogenic keratocysts, in particular the differences found between orthokeratinized keratocysts and parakeratinized keratocysts.     

PTCH mutations in sporadic and Gorlin-syndrome-related odontogenic keratocysts

Odontogenic keratocysts are relatively common lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (or Gorlin syndrome). The PTCH gene has been reported to be associated with Gorlin syndrome. We investigated 10 cases of non-syndromic keratocysts and two other cases associated with Gorlin syndrome, looking for PTCH mutations. Four novel and 1 known PTCH mutations were identified in five individual patients. Of the 5 mutations identified, 2 were germ-line mutations (2619C>A; 1338_1339insGCG) in 2 cysts associated with Gorlin syndrome, and 3 were somatic mutations (3124_3129dupGTGTGC; 1361_1364delGTCT; 3913G>T) in 3 non-syndromic cysts. This report describes PTCH mutations in both non-syndromic and Gorlin-syndrome-related odontogenic keratocysts in Chinese patients, and suggests that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts.     

Lectin histochemistry of ameloblastomas and odontogenic keratocysts

The cell membrane carbohydrate components of 10 simple (follicular and/or plexiform pattern) and 5 acanthomatous ameloblastomas, one plexiform unicystic ameloblastoma, one soft tissue ameloblastoma and 11 odontogenic keratocysts were studied in paraffin-embedded tissues using horseradish peroxidase-conjugated lectins. The presence of glucose and mannose was demonstrated by intense labelling with Concanavalin ensiforme (Con A) in 73% of the ameloblastomas examined, while periodate oxidation of the specimens prior to Con A (PA/Con A) stained 53% of the cases. Ameloblastomas did not express receptors for Triticum vulgaris (WGA), Erythrina chrystagalli (ECA), Arachis hypogea (PNA), and Ulex europaeus (UEA-1). The plexiform unicystic ameloblastoma and the soft tissue ameloblastoma examined showed the same cell membrane glycoproteins as the simple and acanthomatous ameloblastomas. Forty-five per cent of the keratocysts demonstrated Con A reactivity from the basal to the keratinized layer, while 72% of these specimens showed positive PA/Con A reactivity from the parabasal to the keratinized layer. Staining with WGA, ECA, PNA, and UEA lectins also revealed the presence of N-Acetyl-glucosamine and fucose oligosaccharides in the plasma membrane of basal, spinous and keratinized cell layers of the odontogenic keratocysts. The distinct cell surface carbohydrate composition of the ameloblastoma and odontogenic keratocyst may be responsible for the differences in biological behavior in these conditions.     

成纤维细胞生长因子受体3在牙源性肿瘤中的表达

目的:探讨成纤维细胞生长因子受体3(FGFR3)在牙源性肿瘤中的表达状况。方法:采用免疫组化方法,检测FGFR3在正常牙囊或残余牙板上皮和牙源性造釉细胞瘤、角化囊肿及始基囊肿中的表达。结果:FGFR3在造釉细胞瘤、角化囊肿及始基囊肿中呈阳性表达,表达率分别为59%、45%、8%,三者表达差异有显著性。FGFR3在正常牙囊或残余牙板上皮中呈阴性表达。FGFR3阳性细胞集中在肿瘤的细胞成熟区。结论:FGFR3可能与造釉细胞瘤、角化囊肿的发病机制及终末分化机制有关。     

牙源性角化囊肿细胞增殖抗原和表皮生长因子受体表达

目的　探讨牙源性角化囊肿衬里上皮细胞的增殖特点。方法　采用免疫组化染色方法 ,对牙源性角化囊肿、成釉细胞瘤、含牙囊肿、正常口腔粘膜上皮中细胞增殖抗原 Ki- 6 7和表皮生长因子受体 (EGFR)的表达进行分析比较。结果　牙源性角化囊肿中 Ki- 6 7表达较含牙囊肿高 ,与正常口腔上皮相似 ;复发的与未复发的牙源性角化囊肿 Ki- 6 7指数无显著性差异。牙源性角化囊肿中 EGFR表达呈阳性。结论　牙源性角化囊肿上皮增殖活跃 ,上皮增殖生长可能与表皮生长因子家族有关。     

Jaw cyst-Basal cell nevus-Bifid rib syndrome: a case report

Jaw cyst-Basal cell nevus-Bifid rib syndrome or Gorlin-Goltz syndrome involves multiple organ system. The most common findings include multiple odontogenic keratocysts in the jaws and basal cell nevus on the skin that have an early age onset. These multiple odontogenic keratocysts warrant aggressive treatment at the earliest because of the damage and possible complications associated with them. Recurrence in these lesions is the most characteristic feature that has to be taken in consideration while explaining the prognosis to the patient. A case report of a child affected with Gorlin-Goltz syndrome diagnosed, treated and followed at this hospital is presented here.     

Discrimination of ameloblastomas from odontogenic keratocysts by cytokine levels and gelatinase species of the intracystic fluids

In the present study, we measured the levels of the cytokines and gelatinase species in the fluids of ameloblastomas and odontogenic keratocysts, and showed that ameloblastomas can be distinguished from odontogenic keratocysts by the use of these biochemical data. We found that interleukin (IL)-1alpha and IL-1beta levels in the intracystic fluids of ameloblastomas were significantly lower than those in the fluids of odontogenic keratocysts, while IL-6 levels in the fluids of ameloblastomas were significantly higher than those in the fluids of odontogenic keratocysts. On the other hand, no significant differences in tumor necrosis factor (TNF)-alpha levels of the fluids were detected between ameloblastomas and odontogenic keratocysts. An immunohistochemical study revealed that the staining intensity of IL-1alpha, IL-1beta and TNF-alpha in the tumor cells of ameloblastomas was significantly weaker than that in the epithelial cells of odontogenic keratocysts, while the staining intensity of IL-6 in the tumor cells was significantly stronger than that in the epithelial cells of odontogenic keratocysts. Gelatin zymography of the fluids showed that only a small amount of pro-MMP-9 was detected in ameloblastomas, while both pro-MMP-9 and the active form of MMP-9 were detected in 8 of 10 cases of odontogenic keratocysts. Thus, ameloblastomas can be distinguished from odontogenic keratocysts by measuring IL-1alpha and IL-6 levels, and gelatinase species in the fluids.     

Multiple odontogenic keratocysts of the jaws

Single odontogenic cysts are very well documented in the literature. Of those less common reports concerning multiple jaw cysts, many have been associated with systemic conditions or syndromes such as Gorlin-Goltz or basal cell naevus syndrome, Hunter's syndrome and mucopolysaccharidosis, for example, Maroteaux-Lamy syndrome. A case of multiple odontogenic keratocysts unassociated with any syndrome is reported so as to add to the growing number of such cases in the literature. The possibility of this case being a partial expression of the Gorlin-Goltz syndrome is discussed.     

Expression of cell cycle and apoptosis-related proteins in sporadic odontogenic keratocysts and odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome.

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin D1 with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.     

Diagnosis of multiple synchronously occurring cystic jaw lesions in 23 patients: prognostic implications related to basal cell nevus syndrome

Objectives We rarely find multiple cystic lesions in the jaw in panoramic radiographs. Most reports of multiple cystic lesions have described keratocystic odontogenic tumors (KOTs) in patients with basal cell nevus syndrome. In this study, we performed radiographic and clinical examinations of patients with multiple cystic jaw lesions found during their first visit to our department to determine the proportion of basal cell nevus syndrome among multiple cystic lesions. Methods Patients who had a panoramic radiograph taken at Okayama University Hospital between 1993 and 2000 were examined. Twenty-three patients with multiple cystic jaw lesions on a first panoramic radiography examination were entered into this study. Results Of the 23 patients, 12 (52.2%) were diagnosed with basal cell nevus syndrome and 11 (47.8%) were not. Of the 14 patients with multiple KOTs, 12 (85.7%) were diagnosed as having basal cell nevus syndrome. Of the nine remaining patients with multiple cystic jaw lesions, only seven had multiple dentigerous cysts and two had multiple simple bone cysts. Cleft palate was observed in four of the 12 patients (33.3%) with basal cell nevus syndrome. Conclusion Diagnosing basal cell nevus syndrome based on multiple cystic jaw lesions carries a high risk of misdiagnosis. A strong possibility exists that patients with multiple jaw KOTs have basal cell nevus syndrome. Furthermore, cleft palate should be considered an important oral finding in basal cell nevus syndrome because its occurrence was relatively frequent in our study.     

An observational retrospective study of odontogenic cyst´s and tumours over an 18-year period in a Portuguese population according to the new WHO Head and Neck Tumour classification

Background Odontogenic cysts and tumours of the jaws represent one of the most prevalent groups of oral-maxillofacial lesions. We aimed to evaluate the clinical and pathological characteristics of a cohort of odontogenic cysts (OC) and odontogenic tumours (OT) of the jaws in a Portuguese population. Material and Methods This observational retrospective study analysed patients diagnosed with either an OC or OT of the jaws at a central hospital of Oporto, Portugal, between 1988 and 2006. Data collected from patients’ files included demographic, clinical, radiological and histopathological information. Recurrence was evaluated using univariate and multivariate analysis. Results The sample consisted of 397 patients, 231 males (58.2%) and 166 females (41.8%), with a mean-age of 36.7±17 years. Twenty-seven patients (6.8%) presented with more than one lesion providing a total of 433 lesions. There were 396 (91.5%) OC, mostly represented by radicular cysts (n=257;59.4%), dentigerous cysts (n=79;18.2%), or odontogenic keratocysts (n=50;11.5%). There were 37 (8.5%) OT, mostly represented by ameloblastomas (n=16;3.7%), and odontomas (n=9;2.1%). The most common initial clinical manifestation was swelling (n=224;51.7%). Recurrence was observed in 30 cases (6.9%), mostly in ameloblastomas (n=6;37.5%) and odontogenic keratocysts (n=12;24%). In the multivariate analysis the diagnosis classification of the lesion was the only independent and significant variable related with the recurrence (P=0.04). Conclusions Radicular cysts were the most commonly occurring type of OC and ameloblastomas the most commonly occurring OT. Amelobastomas and odontogenic keratocysts were the lesions with the highest rates of recurrence. This large sample provides useful information about the frequency profile and characteristics of OC and OT over a period of 18 years, allowing valuable comparison with data from other countries. Key words:Odontogenic cysts and tumours, radicular cyst, dentigerous cyst, odontogenic keratocyst, ameloblastoma, recurrence.