Non-syndromic Keratocystic Odontogenic Tumors Research Articles

KERATOCYSTIC ODONTOGENIC TUMOR OF THE MAXILLARY ANTERIOR REGION MASQUERADING AS A RADICULAR CYST

Keratocystic odontogenic tumor (KCOT) is a benign odontogenic neoplasm which is characterized by aggressive behavior and a high recurrence rate. KCOTs have a predilection for the angle and ascending ramus of the mandible. Maxillary KCOTs are usually associated with nevoid basal cell carcinoma syndrome. Very few cases of non-syndromic KCOT crossing maxillary midline have been reported. In this article, we report a rare case of KCOT which presented as a multilocular radiolucency crossing midline and involving periapical area of maxillary incisors. The lesion thus simulated a periapical cyst. However, the lesion was proved to be a KCOT on histopathology. Thus this report highlights the need for histopathological evaluation of periapical lesions for accurate diagnosis and treatment plan.

Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic keratocystic odontogenic tumors.

The aim of this study was to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in keratocystic odontogenic tumors associated with Gorlin syndrome (SKOTs) and non-syndromic keratocystic odontogenic tumors (NSKOTs), and to establish correlations with the angiogenic index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were selected for the study. The percentage of immunopositive cells for GLUT-1 and GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic index was determined by microvessel count. The results were analyzed statistically using the nonparametric Kruskal-Wallis test and Spearman's correlation test. High epithelial immunoexpression of GLUT-1 was observed in most tumors (p = 0.360). There was a higher frequency of negative cases for GLUT-3 in all groups. The few GLUT-3-positive tumors exhibited low expression of this protein in epithelial cells. No significant difference in the angiogenic index was observed between groups (p = 0.778). GLUT-1 expression did not correlate significantly with the angiogenic index (p > 0.05). The results suggest that the more aggressive biological behavior of SKOTs when compared to NSKOTs may not be related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in glucose uptake by epithelial cells of KOTs and this process is unlikely related to the angiogenic index. GLUT-1 could be a potential target for future development of therapeutic strategies for KOTs.

What surgical treatment has the lowest recurrence rate following the management of keratocystic odontogenic tumor?: A large systematic review and meta-analysis.

Among the different surgical treatments for keratocystic odontogenic tumors (KOTs), there is no single method associated with a zero recurrence rate (RR). Thus, this study aimed to seek the best surgical treatment with the least RR using a weighted event rated meta-analysis. To address our study purpose, a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline was performed. An extensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to identify all relevant articles published without language restrictions from inception to August 2016. Relevant articles were selected based on the following inclusion criteria: prospective, retrospective, and case series studies that assessed various treatments in non-syndromic KOTs in which RRs were included. The predictor variable was treatment groups, namely: enucleation alone, enucleation with peripheral ostectomy, enucleation with Carnoy's solution application, enucleation with cryotherapy, marsupialization alone, decompression followed by residual cystectomy, and resection. The outcome variable was RR. A weighted RR using a random effect model (because of variation in follow-up time) with a 95% confidence interval (CI) was performed. Data analysis was performed using a comprehensive meta-analysis software. A total of 2287 KOTs in 35 studies were included in this analysis. The weighted RR for various treatment techniques was as follows: enucleation alone (23.1%), enucleation with curettage (17.4%), enucleation and Carnoy's solution (11.5%), enucleation plus liquid nitrogen cryotherapy (14.5%), marsupialization alone (32.3%), decompression followed by residual cystectomy (14.6%), and resection (8.4%). The pooled weighted overall RR of KOTs for all different treatments was 16.6%. Radical resection remains the certain option for obtaining the lowest recurrence with KOTs. However, low recurrence accompanies enucleation with application of Carnoy's solution or cryotherapy as the first-line treatment for primary KOTs. Marsupialization (where indicated) must be followed by secondary cystectomy to minimize recurrence. We believe that to achieve the least possible morbidity, resections should be reserved for multiple recurrent lesions and possibly syndromic cases.

The Clinical Features and Expression of bcl-2, Cyclin D1, p53, and Proliferating Cell Nuclear Antigen in Syndromic and Nonsyndromic Keratocystic Odontogenic Tumor.

The aim of this study was to describe the clinical features and expression of bcl-2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT). This descriptive study comprised 5 patients of KCOT associated with NBCCS and 8 patients of nonsyndromic type treated in the Department of Oral Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre between years 1998 and 2011. The clinical features (site, size, treatment, and recurrence), demographic characteristics, and immunohistochemistry results using antibodies of bcl-2, cyclin D1, p53, and PCNA were examined. The association of the antibody expression and the type of KCOT was analyzed using Fisher exact test. Altogether there were 13 patients, 5 with syndromic KCOT (1 patient met 3 major criteria of NBCCS) and 8 with sporadic KCOT. The age range for syndromic KCT was 11 to 21 years (mean 16.00 years, SD 4.36) and 10 to 54 years (median 24.50 years, interquartile range 19.00) for the nonsyndromic KCOT. Tumor recurrence occurred in 3 patients (7.7%); 1 patient from the syndromic and 2 patients from the nonsyndromic. The most positive expression was observed in PCNA for both the syndromic and nonsyndromic samples and the least positive expression involved the p53. PCNA, bcl-2 protein, and cyclin D1 expressions could be useful in evaluating the proliferative activity of the tumor and the aggressiveness of the clinical presentation; however, the authors would propose for larger sample size research for more definitive results.

Heterozygous PTCH1 Mutations Impact the Bone Metabolism in Patients With Nevoid Basal Cell Carcinoma Syndrome Likely by Regulating SPARC Expression

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by bone and skin abnormalities and a predisposition to various tumors. Keratocystic odontogenic tumors (KCOTs), which are common tumors of the jaw that cause extensive damage to the jawbone, are usually accompanied with NBCCS. Germline PTCH1 mutations in NBCCS tumorigenesis have been frequently studied; however, little is known regarding the pathogenesis of bone abnormalities in this disease. This study sought to investigate the mechanism underlying heterozygous PTCH1 mutation-mediated abnormal bone metabolism in patients with NBCCS. Stromal cells were isolated from the fibrous capsules of patients with NBCCS-associated or non-syndromic keratocystic odontogenic tumors and non-syndromic tumor stromal cells without PTCH1 mutations served as controls. Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag-labeled proteomics analysis. Our findings revealed that osteonectin/SPARC expression was significantly downregulated in syndromic stromal cells compared with non-syndromic stromal cells. SPARC expression was even lower in stromal cells carrying PTCH1 protein truncation mutations. PTCH1 siRNA transfection demonstrated that SPARC downregulation correlates with decreased PTCH1 expression. Furthermore, exogenous SPARC promoted osteogenic differentiation of syndromic stromal cells with enhanced development of calcium nodules. In addition, bone mineral density tests showed that patients with NBCCS exhibit weak bone mass compared with sex- and age-matched controls. This study indicates that germline PTCH1 heterozygous mutations play a major role in bone metabolism in patients with NBCCS, in particular in those with PTCH1 protein truncation mutations. SPARC may represent an important downstream modulator of PTCH1 mediation of bone metabolism. Thus, bone mineral density monitoring is critical for patients with NBCCS for prevention of osteoporosis. In addition, surgical procedures on syndromic-associated KCOTs should be performed with consideration of the weaker bone mass in such patients. © 2016 American Society for Bone and Mineral Research.

Pattern of recurrence of nonsyndromic keratocystic odontogenic tumors

To describe and analyze recurrent pattern of KOTs according to time. This retrospective chart study evaluated histologically confirmed nonsyndromic keratocystic odontogenic tumors (KOT) treated at our institutions between 1975 and2012. Mean age at time of diagnosis was 48 years, and male/female ratio was 1.8:1. The typical nonsyndromic KOT lesion was most often found in the posterior mandible, had radiographically smooth borders, and was associated with symptoms and clinical findings, perforated bone, with a thin capsule. Anterior jaw KOT were found more frequently in patients 50 years or older, and maxillary KOTs were more frequently infected. Treatment was enucleation (n= 70) or marsupialization with subsequent enucleation (n= 22). Observation time ranged from 0.5 months to 25 years (mean 53 months). Crude recurrence rate was 29%. Risk of recurrence increased until 7 years after treatment and then remained stable. Patients with impaired general health had a significantly increased risk of recurrence. Tumors in the posterior mandible that had bone perforation and a thin capsule and contained keratin showed increased recurrence rates. Although recurrence rates were similar for both treatment groups, the groups differed in size and tumor site; thus, the results of this study need to be confirmed in a prospective study. Time-dependent recurrence pattern of KOTs is described and analyzed. The following follow-up protocol is suggested for patients with impaired health or large lesions: clinical and radiographic examinations at 2, 4, and 7 years, followed by intervals of 3 to 4 years; for other patients: clinical and radiographic examination at 4, 6, and 8 years, followed by intervals of 3 to 4 years.

Participation of hMLH1, p63, and MDM2 proteins in the pathogenesis of syndromic and nonsyndromic keratocystic odontogenic tumors

To evaluate the expression of hMLH1, p63, and MDM2 in Gorlin syndrome-associated keratocystic odontogenic tumors (SKOTs) and nonsyndromic keratocystic odontogenic tumors (NSKOTs). Seventeen primary NSKOTs, 17 SKOTs, and 8 recurrent NSKOTs were analyzed by using immunohistochemistry. No significant differences in the hMLH1, p63, or MDM2 labeling indices were observed between groups (P = .398; P = .232; P = .426, respectively). Higher hMLH1 immunoexpression was found in the basal layer of primary NSKOTs. Most KOTs exhibited p63 immunoexpression in the upper layers of the epithelium. MDM2 immunoexpression was observed in the upper epithelial layers of SKOTs and recurrent NSKOTs. It was not possible to correlate the immunoexpression of hMLH1, p63, and MDM2 in SKOTs and primary and recurrent NSKOTs, suggesting that these proteins exert independent effects on the development of these groups of tumors.

NCAM (CD56) expression in keratin-producing odontogenic cysts: aberrant expression in KCOT.

ObjectiveTo investigate immunohistochemically the expression of neural cell adhesion molecule (NCAM), which has been identified as a signaling receptor with frequent reactivity in ameloblastomas (AB), in a series of keratin-producing odontogenic cysts (KPOCs).Material and methodsImmunohistochemical expression of NCAM, using a monoclonal antibody, was determined in a series of 58 KPOCs comprising 12 orthokeratinized odontogenic cysts (OOCs) and 46 keratocystic odontogenic tumors (KCOTs), corresponding to 40 non-syndromic KCOT (NS-KCOTs) and 6 syndromic KCOT (S-KCOTs), associated with nevic basocellular syndrome (NBCS).ResultsNCAM expression was negative in all OOCs, but 36.45% of KCOTs exhibited focal and heterogeneous expression at the basal cell level, as well as in basal budding areas and the basal cells of daughter cysts. The latter two locations were especially applicable to S-KCOTs, with focal NCAM reactivity occurring in 66.66% of cases.ConclusionsAberrant NCAM expression, in KCOTs but especially in S-KCOTs, together with its immunomorphological location, suggests that this adhesion molecule and signaling receptor plays a role in the pathogenesis of KCOTs, with a probable impact on lesional recurrence.Electronic supplementary materialThe online version of this article (doi:10.1186/s13005-015-0060-2) contains supplementary material, which is available to authorized users.

Matrix metalloproteinase expression in keratocystic odontogenic tumors and primary cells

Keratocystic odontogenic tumors (KCOTs) are locally invasive, rapidly proliferating cystic lesions of the jaw. The bone-invasive nature of these tumors has been previously associated with the expression of matrix metalloproteinases (MMPs), which degrade the extracellular matrix. The purpose of this study was to assess the expression and activity of MMPs in primary KCOT cells and tumor tissue. Methods: Four independently established KCOT primary cell populations were grown in Dulbecco’s modified Eagle medium supplemented with 10% FBS and antibiotics. Primary cells were analyzed by qRT-PCR and immunohistochemistry (IHC), and for secretion of active MMPs. Primary tumor sections were analyzed by IHC. Results: Of the 18 human MMPs examined, 9 were consistently expressed in primary KCOT cells. MMP-2 and MMP-14 were highly expressed in all KCOT populations, while MMP-1, 3, 11, 12, 16, 17, and 19 were moderately expressed. MMP-3, 11, 12, 16, 17 and 19 were shown to be expressed in KCOTs for the first time. No significant differences in MMPS profiles were found between syndromic (KCOT-3) and non-syndromic cell populations (KCOT-1/2/4). Protein expression of MMP-1, 11, 12, 14 and 16 was confirmed in each KCOT cell populations by IHC. KCOT-3 cells secreted active MMP-2 as determined by a gel zymography assay. Expression of MMP-1, 2, 3, 11, 12, 14, and 16 was confirmed in matching primary KCOT tumor sections representing syndromic and non-syndromic KCOTs. Conclusion: KCOT primary cell populations and tumors express a wide range of MMPs, which likely play a role in the bone-invasive nature of these tumors.

Patched homolog 1 gene mutation (p.G1093R) induces nevoid basal cell carcinoma syndrome and non-syndromic keratocystic odontogenic tumors: A case report

Mutations in the Patched homolog 1 (PTCH1) gene lead to an autosomal dominant disorder known as nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin syndrome (GS). Several PTCH1 mutations have been observed in NBCCS associated with keratocystic odontogenic tumors (KCOTs), including non-syndromic KCOTs. The missense mutation c.3277G>C (p.G1093R) in exon 19 of the PTCH1 gene has only been reported in non-syndromic KCOTs. The present study reports for the first time a familial case (father and daughter) of NBCCS and KCOTs, carrying the same c.3277G>C (p.G1093R) germline mutation. This observation suggests that this missense mutation is involved in the pathogenesis of NBCCS as well as in a subset of non-syndromic KCOTs. The identification of a missense mutation may lead to an earlier diagnosis of NBCCS.

There is Little Evidence That Other Clinical and Conventional Radiographic Features are Better Than Minimal Buccolingual Expansion for the Diagnosis of Nonsyndromic Keratocystic Odontogenic Tumor

To determine if there are other clinical or conventional radiographic signs available to improve the diagnosis of keratocystic odontogenic tumors compared with using minimal or no buccolingual expansion alone. Information not available. Systematic review. Level 3: Other evidence. Grade C: Consensus, disease-oriented evidence, usual practice, expert opinion, or case series for studies of diagnosis, treatment, prevention, or screening.

Non-syndromic keratocystic odontogenic tumor involving the maxillary sinus: case report

INTRODUCTION: The odontogenic keratocyst tumor is rarely found in maxilla. CASE REPORT: This article describes a report of a case of a 60-year-old Caucasian female with an asymptomatic growth in the region of the posterior maxilla tumor diagnosed as odontogenic keratocyst. We discuss the diagnosis and workup for this type of injury.