A Clinical, Radiological and Histopathological Review of 74 Ossifying Fibromas.

BACKGROUND: Ossifying fibroma (OF) is a fibro-osseous lesion of the jaws and craniofacial bones. Accurate diagnosis can be challenging due to significant overlap of clinicopathological features. This study aimed to evaluate the clinical, radiological and histological features that can aid in diagnosis and identify characteristics that allow categorisation into the three subtypes: juvenile trabecular, psammomatoid and cemento-ossifying OF. METHODS: A total of 74 cases of OF were systematically reviewed for their principle features. Of these, 46 cases were evaluated for their radiographic features including size, location and relationship to the teeth. Histological assessment and stereological point counting were performed in 69 cases to assess the pattern, type and proportion of calcification, the nature of the stroma, the border of the lesion and the presence of secondary changes. Fisher's exact test and Chi-squared tests were used to determine associations between clinicopathological parameters and maxillary, mandibular, odontogenic, non-odontogenic and psammomatoid or trabecular lesions. RESULTS: OF showed a female predilection (F: M; 2:1) and a slight bimodal age distribution with peaks in the second (23%) and fourth decades (27%) (Mean age: 32.4 years). 83% of cases presented as an intra-oral swelling, with the mandible being the most common site (73%). Histologically, a range of morphological patterns were seen, with 50% of cases showing mixed trabecular and psammomatoid features. However, there were no significant differences between the variants of OF in terms of age, gender or histological features. CONCLUSION: Histological features of OF cannot be used to differentiate between the subtypes.

The pathology of oral cancer.

The term 'oral cancer' describes a range of malignancies that may arise in and around the oral cavity. Over 90% of such lesions are squamous cell carcinomas, but even these may be divided into different entities based on site, aetiology and prognosis. In particular, squamous carcinomas in the oral cavity (oral cancer) should be regarded as a different disease to carcinomas arising in the oropharynx. Oropharyngeal cancer is associated with infection by human papillomavirus (HPV) and shows different clinical and histological features. This short review summarises the pathology of oral and oropharyngeal cancer, and describes some of the main prognostic factors that pathologists use to assist clinicians in planning appropriate management.

Screening for mouth cancer: the pros and cons of a national programme.

The paper highlights the pros and cons of a national programme for screening for oral cancer. It provides an overview of screening methods and the metrics used to evaluate a screening programme. It then reviews the evidence for mouth cancer screening against the criteria of the United Kingdom National Screening Committee.

Educational aspects of oral cancer.

The incidence of oral and oropharyngeal cancer is rising in the UK, its aetiology is changing and early detection and referral saves lives. This article covers how and to what depth oral and oropharyngeal cancer is taught to dental students and other preregistration dental care professionals and examines the threats in the current climate to that education. It also discusses the knowledge of oral and oropharyngeal cancer among general dental practitioners and argues that further continuing professional development regarding the changing aetiology and epidemiology of oral and oropharyngeal cancer is desirable. The article concludes that current levels of education before registration must be maintained so that dentists and dental care professionals can take full advantage of continuing professional development and are able to detect oral and oropharyngeal cancer, refer for specialist treatment and provide appropriate preventive advice to their patients. In this way the potential of all dental professionals to save lives will be maintained.

Using virtual microscopy to deliver an integrated oral pathology course for undergraduate dental students.

Dental students in the United Kingdom usually study histopathology as part of their undergraduate curriculum and this has traditionally been delivered using light microscopes in laboratory classes. Beginning in 2005, the oral pathology course in Sheffield was gradually modified by the introduction of virtual microscopy with a focus on creating a more integrated, clinically orientated and dynamic approach to student teaching and learning in histopathology. The purpose of this paper is to describe how virtual microscopy has been used to enhance dental students' learning of oral pathology, and its role in facilitating an integrated oral disease curriculum in Sheffield.

DNA ploidy and cell cycle protein expression in oral squamous cell carcinomas with and without lymph node metastases.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most frequently occurring malignant tumour in the oral cavity. OSCC arises because of multiple genetic alterations. Cell cycle aberrations and aneuploidy are reportedly among the main characteristics of cancer cells and are associated with aggressive growth and poor prognosis. METHODS: The study sample included 47 non-metastasised and 39 metastasised primary OSCC, with matched positive cervical lymph nodes and 17 normal oral mucosa samples. Tissue microarrays (TMAs) were prepared with a minimum of three cores from each case. TMA sections were cut and immunostained with MCM2, Ki-67, geminin and cyclin D1 antibodies. DNA image analysis was performed on the whole tissue section before TMAs were created. RESULTS: The results revealed that there were no differences in cell cycle protein expression in different areas of the tumours or between the metastatic and non-metastatic carcinomas. None of the cell cycle proteins showed significant differences between the lymph node metastasis and the primary OSCC, except for Ki-67. Geminin/Ki-67 ratio showed significant difference between metastatic and non-metastatic tumours. Aneuploidy was detected in all (100%) cases of OSCC. Similarly, all lymph node samples (39 cases) were aneuploid. CONCLUSION: The results suggest that although there was dysregulation of cell cycle regulatory proteins, only Ki-67 and the MCM2/Ki-67 and geminin/Ki-67 ratios may have prognostic significance in oral cancer. DNA ploidy alone was not specific and may not be a good tool to evaluate prognosis or metastatic progression in oral cavity carcinomas.

Second opinion reporting in head and neck pathology: the pattern of referrals and impact on final diagnosis.

OBJECTIVE: There is a need for second opinion histopathology referrals, especially for patients with head and neck pathology. The objective of this study was to determine the pattern and potential impact of referrals to a specialist oral and maxillofacial pathologist. STUDY DESIGN: Retrospective analysis of 566 consecutive referrals with demographic and clinical information was performed. The original diagnosis and the specialists' second opinion diagnosis were compared to assess for discrepancies and potential effect on patient management. RESULTS: Seventy-five percent of cases were referred by general pathologists. Salivary gland (30%) and odontogenic tumors (12%) were the most commonly referred categories. Of the referred cases, 58 (9%) resulted in a significant change in diagnosis, impacting patient management. In 24 cases (4%) the diagnosis was revised from benign to malignant, and in 22 (4%) from malignant to benign. CONCLUSION: This study highlights the need for referrals to oral and maxillofacial pathologists. A second opinion may assist in accurate diagnosis and patient management.

Cribriform adenocarcinoma of the minor salivary glands arising in the epiglottis--a previously undocumented occurrence.

A 39-year-old female was referred to her local Ear, Nose, and Throat department with tonsillar hypertrophy. During intubation for a tonsillectomy, a mass was also noted on the epiglottis. Histopathologic examination showed this mass to be a cribriform adenocarcinoma of the minor salivary glands (CAMSG). As far as the authors are aware, a CAMSG has never been documented in the larynx.

Solitary myofibroma of the adult mandible: a case report.

A 43-year-old woman presented with a swelling in the anterior mandible appearing radiographically as a well-defined radiolucency causing mobility of the anterior teeth. A clinical diagnosis of a radicular cyst led to removal of the lesion and the associated mobile teeth. Postoperative histopathology led to a diagnosis of intraosseous solitary myofibroma of the mandible. Solitary lesions of myofibroma are exceedingly rare in adult jaws, with only 3 previously documented cases.

PLUNC protein expression in major salivary glands of HIV-infected patients.

OBJECTIVE: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. METHODS: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non-specific sialadenitis, and 30 HIV-negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV-negative group was performed. RESULTS: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV-negative cases. CONCLUSIONS: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non-HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.

A qualitative study examining the experience of primary care dentists in the detection and management of potentially malignant lesions. 1. Factors influencing detection and the decision to refer.

BACKGROUND AND AIMS: Many oral squamous cell carcinomas present as late stage disease and so the detection of early and pre-malignancy is considered to be of paramount importance. The majority of research examining primary care dentists' experience of the detection and management of early disease has been undertaken using questionnaires, with the inherent bias this introduces. The aim of this study was to use qualitative methods to develop a richer account of practitioners' views about screening and what factors influence the decision to refer a patient. METHODS: Semi-structured interviews were undertaken with eighteen dentists in Sheffield, transcribed and analysed using thematic analysis. Ten codes were identified according to the aims of the study and organized into four overarching themes. RESULTS: Although many dentists were screening regularly, some did not appear to be adopting a rigorous and systematic approach. A number of participants also placed more reliance on 'classical' presentations rather than the more varied presentation of potentially malignant lesions and were more influenced by the clinical history of the lesion rather than risk factors. CONCLUSION: Overall, the present research suggests that for some dentists, more rigour is required when examining for early disease.

A qualitative study examining the experience of primary care dentists in the detection and management of potentially malignant lesions. 2. Mechanics of the referral and patient communication.

BACKGROUND AND AIMS: The diagnosis of early and pre-malignant lesions of oral squamous cell carcinoma is of paramount importance given the mortality rate of late stage disease. Although studies have been undertaken examining how dentists manage and refer potentially malignant lesions, the majority of the research has used questionnaires, with the inherent bias this introduces. The aim of this study was to use qualitative methods to understand in more detail how practitioners manage potentially malignant lesions once they have been discovered. METHODS: Semi-structured interviews were undertaken with eighteen dentists in Sheffield, transcribed and analysed using thematic analysis. RESULTS: Five codes were identified relating to the mechanics of the referral, the management of the lesion and the patient's risk factors. Health promotional activities were not being undertaken by all the participants and for some, explaining positive results and giving advice about alcohol was perceived as particularly difficult. CONCLUSION: Overall, the present research suggests that further training is required to help dentists broach difficult issues with their patients.

Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas.

Proteins necessary for the normal regulation of the cell cycle include minichromosome maintenance protein 2 (Mcm2) and geminin. These are overexpressed in several premalignant and malignant tumours. The Mcm2/Ki67 ratio can be used to estimate the population of cells that are in early G(1) (licensed to proliferate), and the geminin/Ki67 ratio can determine the relative length of G(1). A high ratio indicates a short G(1) and a high rate of cell proliferation. Mcm2 and geminin have been scarcely explored in oral epithelial dysplasia (OED) and oral squamous-cell carcinoma (OSCC). The purpose of this study was to identify the expression pattern of Mcm2, Ki67 and geminin in normal oral mucosa (NOM), OED and their subsequent OSCC, to determine if expression could help predict the prognosis of OED. Paraffin sections of 41 OED cases that progressed to carcinoma, 40 OED without malignant progression, 38 OSCC and 15 NOM were immunostained with antibodies against Mcm2, geminin and Ki67. Labelling indices (LIs) increased progressively from NOM, OED and OSCC (Mcm2, P<0.001; geminin, P<0.001 and Ki67, P<0.001). In all the OED cases (n=81) the levels of expression of Mcm2 (LI, 73.6), geminin (LI, 24.4) and Ki67 (LI, 44.5) were elevated indicating a constant cell-cycle re-entry. When the OED groups were compared, Mcm2 protein expression was higher in the OED with malignant progression (P=0.04), likewise there was a significant increase in the Mcm2/Ki67 and geminin/Ki67 ratios (P=0.04 and 0.02 respectively). Mcm2 and geminin proteins seem to be novel biomarkers of growth and may be useful prognostic tools for OED.

DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression.

Abnormal DNA content (aneuploidy) has been associated with malignant and premalignant epithelial lesions. The presence of aneuploidy in tumours at an early stage and in dysplastic lesions suggests that analysis of DNA content may be a useful marker for determination of prognosis in these lesions. The aim of this study was to use DNA image cytometry to evaluate aneuploidy in oral dysplastic lesions and to determine whether aneuploidy is associated with malignant progression. Forty-two lesions of oral epithelial dysplasias (OED) that had progressed to oral squamous cell carcinoma (OSCC) and 44 lesions that did not progress were analysed for DNA ploidy using image cytometry of nuclear monolayers prepared from paraffin-embedded tissue. Forty-two OSCC that had arisen from the OED cases and five samples of normal oral mucosa samples (NOM) were also examined. Aneuploidy was found in 14/42 (33.3%) of the OED that progressed, but in only 5/44 (11.3%) of OED that did not progress (p=0.01). A total of 19 OED were aneuploid of which 74% showed malignant progression compared to only 42% of the diploid lesions. The sensitivity and specificity of DNA image cytometry to detect cases with high risk of malignant progression was 0.33 and 0.88, respectively. The PPV and NPV were 0.74 and 0.58. We conclude that aneuploid oral dysplastic lesions have a high risk of malignant progression and that DNA image cytometry might help to identify those lesions most at risk.

Sebaceous carcinoma of the parotid gland in children: an immunohistochemical and ploidy study.

Sebaceous carcinoma (SC) is a rare malignancy, affecting mainly the periocular glands. To the best of the authors' knowledge, this is the first English-language report of parotid SC affecting children; two cases are presented. Immunohistochemical studies included 29 different antibodies (15 of these were cytokeratins, CKs). For each case, DNA ploidy status was determined using isolated nuclei stained with Feulgen and analysed using a DNA image cytometry system. Most of the tumour cells were positive for CKs AE1/AE3, 34B12, 5 and 7. The CK14 pattern depicted the monolayer of basal cells surrounding the islands of malignant tissue, while the more central sebaceous differentiated cells were negative. Epithelial membrane antigen was strongly positive in the well differentiated cells, while most of the basaloid peripheral cells were negative, and only a few cells were positive for carcinoembryonic antigen. beta catenin, E cadherin and C-erb B2 were expressed by most of the cells including the more differentiated sebaceous cells. Tumour cells were negative for muscle or myoepithelial markers, androgen, oestrogen and progesterone receptors. Both SCs were uniformly diploid, and showed low proliferative indices for p53, Ki-67 and Mcm-2, which is consistent with the good clinical course presented by these patients so far.

Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours.

BACKGROUND: Recent studies have proposed that minichromosome maintenance (Mcm) proteins may be sensitive proliferation markers and may serve as novel biomarkers for prognostication and diagnosis of various pre-malignant and malignant lesions. The aims of this study were to determine the expression of Mcm-2, Ki-67 and geminin in salivary gland (SG) tumours, and to evaluate their usefulness for diagnosis or for prediction of tumour behaviour. METHODS: Tissue from 62 SG tumours was assembled in tissue microarray format. There were 13 adenoid cystic carcinomas (ACC), 10 carcinoma ex pleomorphic adenomas (CEPA), 10 mucoepidermoid carcinomas (MEC), 10 polymorphous low-grade adenocarcinomas (PLGA), 10 pleomorphic adenomas (PA) and nine acinic cell carcinomas (AcCC). Clinicopathological data were collected retrospectively and immunohistochemical analyses of Mcm-2, Ki-67 and geminin were performed on all lesions. Labelling index (LI) for each marker was determined by counting the percentage of positive cells in six random fields from three arrays per case. RESULTS: Mcm-2 expression was higher than Ki-67 and geminin in all tumours studied. Mcm-2 LI was higher in ACC (28.2 +/- 19.2%) than in CEPA, AcCC, MEC, PA and PLGA (5.3 +/- 4.1%, P = 0.001). Mcm-2 LI was higher in CEPA (20.4 +/- 5.0%) than in PA (6.9 +/- 5.0%, P = 0.001). LI did not correlate to tumour grade or outcome for any of the markers or tumour types. CONCLUSIONS: The findings suggest that Mcm-2 may be a sensitive proliferation marker in SG tumours and may be useful for differential diagnosis between PA and CEPA, and ACC and PLGA. Further studies are warranted to assess the value of Mcm-2 as a predictor of recurrence and survival.

Oral and pharyngeal cancer in South Asians and non-South Asians in relation to socioeconomic deprivation in South East England.

From UK Thames Cancer Registry data, after controlling for socioeconomic deprivation of area of residence, South Asian males showed a higher relative risk of oral (1.36; 95% CI: 1.11, 1.67), but not of pharyngeal cancer than non-South Asian males, whereas South Asian females had much higher risks of these cancers (3.67; 95% CI: 2.97, 4.53 and 2.06; 95% CI: 1.44, 2.93), respectively, than non-South Asians.

Expression of PLUNC family members in benign and malignant salivary gland tumours.

OBJECTIVES: The aim of this study was to determine the expression of PLUNC proteins in benign and malignant salivary gland tumours and thus their potential use as diagnostic and / or prognostic tools. MATERIALS AND METHODS: A tissue microarray was assembled from 64 salivary gland tumours including adenoid cystic carcinoma, carcinoma ex-pleomorphic adenoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, pleomorphic adenoma, acinic cell carcinoma, myoepithelial carcinoma and papillary cystadenocarcinoma. Clinicopathological data were collected retrospectively and immunohistochemical analysis of three PLUNC proteins (SPLUNC1, SPLUNC2 and LPLUNC1) was performed. Immunoreactivity was assessed as positive or negative. RESULTS: PLUNC expression was only found in mucoepidermoid carcinomas and papillary cystadenocarcinoma; all other tumours studied were negative. Mucin plugs, mucous and intermediate cells of mucoepidermoid carcinomas were positive for LPLUNC1 and SPLUNC2, but areas composed of epidermoid and clear cells were negative for all PLUNCs. Papillary cystadenocarcinoma was positive for all PLUNCs. No correlation was found with tumour grade or outcome. CONCLUSIONS: Intense expression of two PLUNC proteins in mucous cells and mucin plugs of mucoepidermoid carcinoma and papillary cystadenocarcinoma indicate that they could be used as additional diagnostic tools in some equivocal cases, but further studies are needed to understand the biological processes involved in PLUNC expression.

The range and demographics of salivary gland tumours diagnosed in a UK population.

Salivary gland tumours are relatively rare and comprise a diverse range of neoplasms. The aim of this study was to determine the range and demographics of all histologically diagnosed salivary tumours in a European population. All entries for salivary gland tumours from 1974 to 2005 inclusive were retrieved and analysed for each diagnosis including number of specimens, male:female ratio and age range. These data were then analysed for the distribution of benign and malignant salivary tumours in major and minor salivary glands. 58,880 specimens were received; of these, 741 cases (1.3% of all specimens) were diagnosed as salivary gland tumours with a male to female ratio of 0.7:1. There were 481 (64.9%) benign and 260 (35.1%) malignant neoplasms, with the most common tumours being pleomorphic adenoma and mucoepidermoid carcinoma, respectively. Our study provides demographic data on a large series of salivary gland tumours in a European population. Accurate diagnosis is essential as salivary lesions have diverse clinical and prognostic outcomes. This study has confirmed that some tumours have a predilection for certain sites and that the risk of malignant disease is also greater at specific sites within the oral cavity.