Lateral dermoid cyst.
This is an unusual case of a lateral dermoid cyst that caused some diagnostic confusion.
Biomedical subjects
Publications and source records attributed to Philip Sloan.
This is an unusual case of a lateral dermoid cyst that caused some diagnostic confusion.
PURPOSE: Fragile histidine triad (FHIT) expression in precursor oral lesions (POL) and oral squamous cell carcinomas (OSCC) was studied with regard to (a) the frequency of loss of FHIT expression, (b) whether loss of FHIT expression correlates with degree of dysplasia in POLs, (c) whether FHIT loss predicts high-risk POLs that are more likely to transform, and (d) whether FHIT loss in OSCCs correlates with survival. EXPERIMENTAL DESIGN: Ninety-four POLs and 86 OSCCs were immunostained for FHIT. Survival analysis was done for cases with validated clinical outcomes. RESULTS: By optimizing the immunostaining protocol, we found that FHIT is expressed in a distinctive strong nuclear and weak cytoplasmic pattern in oral tissues. Loss of FHIT expression was found in 42 of 94 (45%) POLs and in 66 of 86 (77%) OSCCs. We observed a statistically significant positive correlation between frequency of FHIT loss and increasing grade of dysplasia (chi2=13.8; degrees of freedom=4; P=0.008). Loss of FHIT expression in POLs that progressed to malignancy was more frequent than in those that did not [17 of 25 (68%) versus 12 of 29 (41.4%), respectively]. This difference was statistically significant (chi2=3.8; degrees of freedom=1; P=0.046). In OSCCs, loss of FHIT staining indicated a worse prognosis (survival rate, 36.2%) than when positive FHIT staining was observed (survival rate, 50%), but the difference was not statistically significant (P=0.546, Kaplan-Meier, log-rank). CONCLUSIONS: FHIT seems to localize to both nuclear and cytoplasmic domains. FHIT inactivation occurs early in oral carcinogenesis and may be useful molecular marker for progressive dysplastic oral lesions.
OBJECTIVES: To compare the effect of real acupuncture and sham acupuncture in the treatment of temporomandibulat joint myofascial pain, in order to establish the true efficacy of acupuncture. METHODS: A double blind randomised controlled trial conducted in the TMD Clinic, at the School of Dentistry, The University of Manchester. Twenty-seven patients were assigned to one of two treatment groups. Group 1 received real acupuncture treatment whilst Group 2 received a sham acupuncture intervention. Both the assessor and the patient were blinded regarding the group allocation. Baseline assessment of the outcome variables was made prior to the first treatment session, and was repeated following the last treatment. RESULTS: The results demonstrated that real acupuncture had a greater influence on clinical outcome measure of TMJ MP than those of sham acupuncture, and the majority of these reached a level of statistical significance. CONCLUSION: Acupuncture had a positive influence on the signs and symptoms of TMJ MP. In addition, this study provides evidence that the Park Sham Device was a credible acupuncture control method for trials involving facial acupoints.
The present study attempted to assess the reasons behind the inter-observer variation in grading oral epithelial dysplasia (OED). Three oral pathologists and one general pathologist examined 68 histological slides of OED lesions of variable grade for scoring the presence of each individual characteristic of the architecture and cytology changes that were established by the 2005 WHO classification. The assigned features in each case were correlated with clinical outcomes to understand which features are more commonly associated with malignant transformation. Interestingly, for all individual characteristics, the pairwise inter-examiner and group kappa values ranged from poor to moderate. It appeared that for each characteristic separately there was much dissension. Despite these observations, comparing these data with that from our previous paper on the same slides showed that the inter-observer agreement on the degree of dysplasia either by using the new binary system of "low-risk" or "high-risk" or by using the 2005 WHO classification turned out to be better than the agreement on the individual characteristics of architecture and cytology changes. Certain features show significant association with the clinical outcomes. In the discussion, some explanations to help understanding the sources of variation in grading OED are put forward. In conclusion, grading dysplasia is not an exact science and pathologists are doing their best to reach optimal results. Improvement in the standard of the histopathology reporting of OED lesions could be achieved by consideration of several issues. Of these, there is need for a universal definition of the architectural and cytological features that are the basis of any OED grading process. A minimum dataset for reporting OED lesions should be set up. Also, the use of a consensus scoring process between two or more observers should be encouraged as this would improve inter-observer agreement.
The aim of this paper is to assess the reproducibility of a novel binary grading system (high/low risk) of oral epithelial dysplasia and to compare it with the WHO classification 2005. The accuracy of the new system for predicting malignant transformation was also assessed. Ninety-six consecutive oral epithelial dysplasia biopsies with known clinical outcomes were retrieved from the Oral Pathology archives. A pilot study was conducted on 28 cases to determine the process of classification. Four observers then reviewed the same set of H&E stained slides of 68 oral dysplastic lesions using the two grading systems blinded to the clinical outcomes. The overall inter-observer unweighted and weighted kappa agreements for the WHO grading system were Ks = 0.22 (95% CI: 0.11-0.35), Kw = 0.63 (95% CI: 0.42-0.78), respectively, versus K = 0.50 (95% CI: 0.35-0.67) for the new binary system. Interestingly, all pathologists showed satisfactory agreement on the distinction of mild dysplasia from severe dysplasia and from carcinoma in situ using the new WHO classification. However, assessment of moderate dysplasia remains problematic. The sensitivity and specificity of the new binary grading system for predicting malignant transformation in oral epithelial dysplasia were 85% and 80%, respectively and the accuracy was 82%. The new binary grading system complemented the WHO Classification 2005 and may have merit in helping clinicians to make critical clinical decisions particularly for the cases of moderate dysplasia. Histological grading of dysplasia using established criteria is a reproducible prognosticator in oral epithelial dysplasia. Furthermore, the present study showed that more consensus scoring on either the degree of dysplasia, assessment of risk or the presence of each morphological characteristic by a panel should be encouraged.
Fifty healthy volunteers were studied to assess the potential applications of oral brush sampling using liquid-based cytology. Three specimens from the buccal mucosa and lateral border of tongue were collected from each subject by using cervical brushes and brooms. The brush was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer's directions (SurePath, UK). Slides were stained by the Papanicolaou method and assessed for squamous cell adequacy by the same criteria used for cervical cytology screening. Immunocytochemical staining for FHIT (Fragile Histidine Triad) was applied in liquid-based preparations following the streptavidin-biotin-peroxidase method. Human papillomavirus (HPV) detection was performed using the Hybrid Capture 2 assay (Digene) and the PCR-based Roche AMPLICOR HPV Test. LBC preparation slides showed good sample preservation, specimen adequacy and visualization of cell morphology. Interestingly, nine cases showed borderline cytological abnormalities from apparently normal oral mucosa. All cases showed good quality positive FHIT immunoreactivity staining. All studied cases were high-risk HPV negative using HC2 assay method. However, the AMPLICOR Roche Test detected four samples with positive results for high-risk HPVs. Liquid-based cytology has potential as a screening tool for oral cancer and precancer. The method may also have applications for research and practice in the field of oral cancer and precancer. However a special custom-designed oral cytobrush is required.
An otherwise-healthy 11-month-old white girl presented with a polyp-like lesion on the anteromedial part of the maxillary alveolar ridge. It looked like a congenital epulis, but histological examination showed fascicles of smooth muscle cells dispersed in collagenous stroma with a few peripheral nerve bundles that were intermingled with smooth muscle fibres. The muscle cells stained strongly for desmin and alpha-smooth-muscle actin. However, S-100 was found only in peripheral nerve bundles. It was therefore a leiomyomatous hamartoma.
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Worldwide, oral cancer has one of the lowest survival rates. It is well recognized that survival rates are improved if the disease is treated in its early stages. The aim of this study was to assess the effectiveness of screening methods in decreasing the mortality of oral cancer. A systematic review on the effectiveness of oral cancer screening was performed using all publications in MEDLINE, CANCERLIT, EMBASE, and Cochrane CCTR between 1966 and September 2002. The evidence was evaluated using the standardized methodology of the Cochrane Collaboration. The search strategy revealed 1,389 citations. From these, 100 potentially relevant articles were selected for review. However, only one randomized controlled study using visual examination as the method for screening fulfilled the selection criteria. Given the limitation of evidence and the potential methodological weakness in the included study, it is valid to say that there is no evidence to recommend inclusion or exclusion of screening programs for oral cancer using visual examination in the general population. In addition, no robust evidence exists that indicates whether other screening methods including toluidine blue, fluorescence imaging, or brush biopsy are either beneficial or harmful. Further high-quality studies to assess the efficacy and effectiveness of screening are required. Additional investigations aimed at elucidating the natural history of oral cancer and evaluating the effectiveness of prevention and opportunistic screening in high-risk groups are needed. A greater understanding of the genetic basis of oral cancer is an essential prerequisite to the development of molecular markers for screening.
The aim of this review is to establish the effectiveness of stabilization splint (SS) therapy in reducing symptoms in patients with myofascial pain. Searching of electronic databases, handsearching of relevant key journals, and screening of reference lists of included studies were undertaken. There was no language restriction, and unpublished research was sought. The selection criteria were randomized controlled trials comparing splint therapy to either no treatment or another active treatment. Data extraction and validity assessment were carried out independently and in duplicate. Studies were grouped according to treatment type. Twenty potentially relevant Randomized Controlled Trials (RCTs) were identified. Only twelve met the inclusion criteria. There is insufficient evidence either for or against the use of stabilization splint therapy over other active interventions for the treatment of temporomandibular myofascial pain. However, it appears that stabilization splint therapy may be beneficial for reducing pain severity at rest and on palpation and depression when compared to no treatment. The authors suggested the need for well conducted RCTs that pay attention to method of allocation, blind outcome assessment, sample size, and duration of follow-up. Various measures were adopted to assess the outcomes of treatment. Standardization of the methods used to measure outcomes of the treatment of myofascial pain should be established in future RCTs.
Allelic imbalance on chromosome arm 8p is common in head and neck squamous cell carcinoma (HNSCC). DLC1, a tumour suppressor gene inactivated in liver carcinogenesis and encoding a Rho GTPase activating protein (RhoGAP) maps to one of the deleted regions (8p21.3-22). In order to determine whether inactivation of DLC1 is involved in HNSCC, we have screened tumour cell lines for DLC1 mutations and expression. Pathological mutations were not identified in any of the 17 cell lines tested. Seven polymorphisms were identified; 13 of the 17 of cell lines were homozygous for all seven polymorphisms compared to only 2 of 17 controls suggesting a loss of heterozygosity in a majority of the cell lines. DLC1 expression was observed in all 11 HNSCC cell lines tested, thus excluding the possibility of transcriptional silencing of DLC1 by promoter hypermethylation. Overall, our data suggest that hemizygous deletions of the DLC1 locus are frequent in HNSCCs but this gene is unlikely to be primary target for inactivation on this chromosomal arm.
We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon-Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early-onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 micro moles/mg/min vs. 1,678.7 +/- SD 527.2 micro moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS.
We and others previously identified a region of hemizygous or homozygous deletion at chromosome band 8p23 in oral and oropharyngeal squamous cell carcinomas (OSCCs) and many other cancer types, suggesting the presence of a tumor-suppressor gene (TSG) in this region. Recently, based on a single region of homozygous deletion in head and neck squamous cell carcinomas (HNSCC), a putative TSG, CUB and sushi multiple domains-1 (CSMD1), has been identified. In the present study, we mapped three OSCC cell lines with previously described homozygous deletions at a high resolution onto a detailed physical map. Critically, this map covered a wider region than that used in previous studies, and in contrast to these studies, our results revealed multiple regions of homozygous deletion within a small interval on 8p23. To investigate this deletion pattern further, we generated a panel of 34 sequence tagged site (STS) markers spanning the region and tested these three cell lines and an additional 34 OSCC cell lines, identifying homozygous deletions in a further four. Combining the results from all seven deleted cell lines identified three non-overlapping regions of homozygous deletion. This complex pattern could be consistent with the presence of multiple TSGs or one very large TSG in this region, and/or specific chromosomal instability. CSMD1 spans two of the three deleted regions and, therefore, would appear to be an excellent candidate for a TSG. However, deletion mapping with STSs corresponding to the exons of CSMD1 shows that some of the deletions do not interrupt its coding region, and in other cell lines the coding region is interrupted by two discontinuous homozygous deletions, suggesting the presence of redundant deletions. These results call into question whether the CSMD1 gene is the 8p23 TSG or whether this or any other genes at this locus are involved in the development of OSCC.
Malignant Triton tumor (MTT) is a malignant peripheral nerve sheath tumor showing rhabdomyoblastic differentiation. It is considered a high-grade neoplasm with poor outcome. This report describes an MTT appearing in the oral cavity. On histologic examination the encapsulated lesion was composed of interlacing fascicles of spindle cells and scattered, large, strap-like pleomorphic cells with abundant eosinophilic cytoplasm. No cross striations were seen. Examination of levels through the tissue showed a total of only 4 normal mitoses and no necrosis. Immunohistochemistry demonstrated diffuse S100 positivity in the spindle cells. The large pleomorphic cells were weakly positive for alpha-sarcomeric actin and myoglobin, although variably but strongly positive for desmin. Management involved a small en bloc resection of the maxilla. After 33 months there was no sign of recurrence or distant metastasis. It was concluded that low-grade variants of MTT occur that do not have an aggressive clinical course.
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Familial melanoma predisposition is associated with germline mutations at the CDKN2A/ARF locus in up to 40% of families. The exact role of the two proteins encoded by this complex locus in this predisposition is unclear. Most mutations affect either CDKN2A only or products of both genes. Recently a deletion affecting ARF-specific exon 1beta was reported in a family with melanoma and neural tumours. However, the possibility of this deletion also altering the CDKN2A transcript could not be excluded. More convincingly, a 16 base pair insertion in exon 1beta has been reported in an individual with multiple melanomas suggesting a direct role for ARF in melanoma predisposition. We report here a splice mutation in exon 1beta in a family with melanoma that results in ARF haploinsufficiency. The mutation was observed in a mother and daughter with melanoma. A sibling of the mother with breast cancer also had this mutation. Analysis of the melanoma from one individual revealed a 62 bp deletion in exon 3 of the wildtype allele and loss of the mutant allele; these somatic changes would affect both CDKN2A and ARF. These somatic events suggest that concomitant inactivation of both ARF and CDKN2A may be necessary for melanoma development and that mutations in ARF and CDKN2A possibly confer different levels of susceptibility to melanoma, with the former associated with lesser predisposition. In this situation, the events follow a 'three-hit' model as observed in tumours from FAP patients with an attenuated phenotype. Overall, the data suggest a direct role for ARF haploinsufficiency in melanoma predisposition and co-operation between ARF and CDKN2A in tumour formation, consistent with recent observations in Cdkn2a-specific knockout mice.
Bone traps vary in design, although the effect of pore size on the nature of the debris collected in vivo has not yet been established. The aims of this study were 1) to compare the clinical performance of two bone collectors during implant surgery, ii) to establish the mass of tissue collected by each device, and iii) to characterize the nature of the collected debris. Thirty-eight patients (paired for implant site) were categorised into three clinical groups according to the site and the number of implants they were to receive. Patients underwent bone collection with the Frios bone trap or the Osseous Coagulum Trap according to a randomisation sequence. The samples were fixed in formalin, frozen, freeze-dried and weighed. Material from each sample was embedded in paraffin wax and stained with haematoxylin and eosin. All sections were examined by optical microscopy and the proportion of bone to coagulum was established histomorphometrically. During surgery, the Frios bone trap blocked once and the Osseous Coagulum Trap blocked 11 times. In all cases where blockage occurred, excess coagulum was apparent. All the samples that were collected by the Frios bone trap contained bone and coagulum, with a mean proportion of 90.6% bone. With regard to the Osseous Coagulum Trap, one sample contained no bone and two samples contained only trace amounts of bone; the remaining samples contained a mean proportion of 67.3% bone. Pore size affects both clinical performance and the histological composition of the debris collected, and this might have important implications if used as an augmentation material.