Delphi study to determine the key qualities consultant histopathologists look for in their trainees.

AIMS: A Delphi study to triangulate and determine the relative importance of the key qualities of trainees identified from qualitative interviews that sought to understand how consultant histopathologists determine diagnostic competences in trainees. METHODS: Twelve participants were purposively chosen for the Delphi to form an expert panel of relevant stakeholders. Participants were asked to score and rank the items presented to them. RESULTS: A total of 22 out of 27 of the key qualities of trainees (items) reached 'consensus in' after round 2 suggesting participants were able to agree that the majority of the items identified in the qualitative interviews were important to diagnostic competence. Five items reached 'no consensus'. Participants did not suggest any additional items. Participants particularly valued qualities of reflection and professionalism and trainees who understood the process of reaching a diagnosis and how their pathological report could impact on patient care. CONCLUSIONS: This study has triangulated findings from our qualitative interviews and show that consultants value a wide variety of qualities when determining diagnostic competence in their trainees. The judgement is complex and is therefore best assessed longitudinally and on a number of cases, so consultants can look for consistency of both approach to diagnosis and of trainee behaviour.

How consultants determine diagnostic competence in histopathology trainees.

AIMS: This is a qualitative study exploring how consultant histopathologists determine diagnostic competence in their trainees. METHODS: Semi-structured interviews were conducted with consultants and trainees and analysed using the Framework Method. RESULTS: Five major themes emerged from the data: process, person, stage of training, trust and time. Within these major themes, there were multiple subthemes which reflect the complex, longitudinal nature of the judgement, as well as the knowledge, skills and attitudes which are most relevant to diagnostic competence. A conceptual framework is proposed to illustrate the judgement ecology, which is supported by anonymised quotes from interview participants. CONCLUSIONS: Our study is the first to explore in depth how consultant histopathologists determine diagnostic competence in their trainees. This is particularly important as histopathology is a unique medical specialty for which there is little evidence to support the current assessment strategies during training. The resulting conceptual model and findings from this study may help to form an evidence base to inform future assessment tools in histopathology.

Odontogenic tumors and lesions treated in a single specialist oral and maxillofacial pathology unit in the United Kingdom in 1992-2016.

OBJECTIVES: Odontogenic tumors (ODTs) are a heterogeneous group of lesions derived from elements of tooth-forming tissues. No detailed data on the incidence of odontogenic tumors in the United Kingdom have been published. The aim of this study was to retrospectively describe the range and incidence of odontogenic tumors from 1992 to 2016 in a single specialist unit and to compare this population with others. STUDY DESIGN: By using the Oral and Maxillofacial Pathology database, Sheffield (UK), we included both local and referred consultation cases. A proportion of diagnoses were reclassified in accordance with the 2017 World Health Organization classification. RESULTS: In total, 559 odontogenic tumors were diagnosed. Overall, the most common lesions were ameloblastoma (196 [33.8%]), odontoma (148 [25.5%]), and odontogenic myxoma (37 [6.3%]), but this varied between local and referral case populations, with odontomas being most common in the local population (43%). The sites affected and the gender and age of patients were similar to other Western populations. Malignant ODTs comprised 33 cases (5.7%), of which 9 (27.3%) were ameloblastic carcinoma. The majority of the malignant ODTs comprised referral cases. CONCLUSIONS: Here, we present the first detailed data on ODTs within a UK population, and the pattern of incidence from the local population is similar to other Western populations. The exceptional rarity of malignant ODTs emphasizes the need for specialist centers for their treatment to gain diagnostic experience.

Assessors' and trainees' perceptions of workplace-based assessments in histopathology.

AIM: Workplace-based assessments (WBAs) are an integral part of specialist medical and dental training in the UK. Histopathology represents a very different training environment to the surgical specialities so it is important to know that the current WBAs are fit for purpose. A literature search revealed very little evidence regarding the perception of WBAs in histopathology. The aim of this study was therefore to assess the current perception of WBAs in histopathology by assessors and trainees. METHODS: A questionnaire was sent to all histopathology assessors and trainees on the Royal College of Pathologists database. Data were analysed using basic descriptive statistics. Free text comments were analysed by thematic analysis. RESULTS: The questionnaire was completed by 242/2175 assessors (response rate 11.1%) and 91/519 trainees (response rate 17.5%). There was no significantly different perception of WBAs between trainers and trainees (p>0.05). Key findings included respondents stating that they strongly disagreed or disagreed WBAs identify diagnostic competence (68% of trainees; 62% of assessors), identify trainees in difficulty (69% of trainees; 64% of assessors) or accurately reflect trainee progress (62% of trainees; 59% of assessors). Analysis of free text comments identified three main issues related to WBAs: their utilisation, purpose and design. CONCLUSION: There was an overall negative perception of WBAs, particularly their perceived regulatory nature. It appears that the current WBAs do not always meet the criteria of a useful test in that they are perceived as being applied variably, produce results with questionable validity and have little apparent educational value.

A Case of Concomitant Pemphigus Foliaceus and Oral Pemphigus Vulgaris.

Pemphigus is a chronic autoimmune condition that can affect multiple areas of the body. The two main subtypes of pemphigus are pemphigus vulgaris (PV) and pemphigus foliaceus (PF) which can rarely occur concurrently or even transition from one to the other. The process of transition may be explained by qualitative changes in desmoglein autoantibody profile. We present a rare case of concomitant PF and oral PV and explore the literature on transitions between pemphigus subtypes and whether this case could represent a transition from PF to PV. Furthermore, the realities of multidisciplinary patient management are discussed.

Constructing Tissue Microarrays: Protocols and Methods Considering Potential Advantages and Disadvantages for Downstream Use.

Tissue microarrays were first constructed in the 1980s but were used by only a limited number of researchers for a considerable period of time. In the last 10 years there has been a dramatic increase in the number of publications describing the successful use of tissue microarrays in studies aimed at discovering and validating biomarkers. This, along with the increased availability of both manual and automated microarray builders on the market, has encouraged even greater use of this novel and powerful tool. This chapter describes the basic techniques required to build a tissue microarray using a manual method in order that the theory behind the practical steps can be fully explained. Guidance is given to ensure potential disadvantages of the technique are fully considered.

High-grade urothelial carcinoma with squamous differentiation metastasizing to the tongue.

Tumors metastasizing to the head and neck region are uncommon. Metastasis of urothelial carcinoma to the maxillofacial region is exceedingly rare and mostly involves the jaw. We present a case of urothelial carcinoma metastasizing to the tongue. Immunohistochemistry in conjunction with fluorescent in situ hybridization was used to confirm the relation between the primary and metastatic lesions, making it the first such reported case employing the UroVysion (Catalogue number 02 J27-025, Abbott Molecular Inc., Des Plaines, IL, USA) fluorescent in situ hybridization probe in a metastatic lesion in the head and neck region.

The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour.

BACKGROUND: Chemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL-8 and growth-related oncogene-α (which selectively binds CXCR2). METHODS: mRNA and protein expression was studied using RT-PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS-based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays. RESULTS: mRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL-8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL-8) and CXCR2 (for GROα) as receptor-blocking antibodies significantly inhibited the responses. IL-8 and GROα also increased MMP-9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP-7 production was only seen in OCCL. CONCLUSIONS: Functional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.

The αE(CD103)ß7 integrin interacts with oral and skin keratinocytes in an E-cadherin-independent manner*.

The integrin αE(CD103)ß7 (αEß7) is expressed by intraepithelial lymphocytes, dendritic cells and regulatory T cells. It plays an important role in the mucosal immune system by retaining lymphocytes within the epithelium and is involved in graft rejection, immunity against tumours and the generation of gut-homing effector cells. In gut and breast, the ligand for αEß7 is E-cadherin but in human oral mucosa and skin, there is evidence that lymphocytes use an alternative, unknown, ligand. In the present study, the I domain of the human αE subunit, which contains the E-cadherin-binding site, was locked in a highly active, 'open' and an inactive, 'closed' conformation by the introduction of disulphide bonds and these domains were expressed as IgG Fc fusion proteins. αE fusion proteins recognize E-cadherin, the only known ligand for αEß7. This interaction was inhibited by an antibody that blocks the αE-binding site on E-cadherin and by the omission of Mn(2+) , which is essential for integrin function in vitro. The locked 'open' conformation of αE adhered to human oral and skin keratinocytes, including the E-cadherin-negative H376 cell line, and this was not inhibited by blocking antibody against the αEß7-binding site on E-cadherin, providing further evidence for the existence of an alternative ligand for αEß7 in skin and oral mucosa. The interaction with E-cadherin and the alternative ligand was Mn(2+) dependent and mediated by the metal ion-dependent coordination site (MIDAS) of the locked 'open'αE I domain, independently of the ß7 subunit.

Functional expression of the chemokine receptor XCR1 on oral epithelial cells.

Chemokines are chemoattractant cytokines which act on specific receptors and play an important role in leukocyte migration as well as physiological and pathological processes. We investigated the role of the chemokine receptor XCR1 and its ligand lymphotactin (Lptn/XCL1) in the regulation of oral epithelial cell behaviour. In vitro XCR1 mRNA and cell surface protein expression was detected in normal oral keratinocytes and oral squamous cell carcinoma cell lines. Lymphotactin mediated intracellular activation of the ERK1/2 signalling pathway and stimulated migration, invasion, and proliferation of all cells through XCR1. Oral cancer cells showed a greater response to lymphotactin than normal keratinocytes and a direct relationship between receptor expression and migration, invasion, and proliferation was observed. Exposure of normal keratinocytes to lymphotactin resulted in increased adhesion to fibronectin but not collagen and stimulated MMP-2 and MMP-9 but not MMP-7 release, whereas exposure of cancer cells resulted in increased adhesion to both collagen and fibronectin and stimulated production of MMP-2, MMP-9, and MMP-7. We observed XCR1 but not lymphotactin to be expressed by epithelial cells in normal oral mucosa in vivo, whilst both were expressed and up-regulated in inflammatory oral disease and oral cancer including primary and metastatic disease. Lymphotactin mRNA and constitutive intracellular protein were detected in normal keratinocytes and oral cancer cell lines in vitro. These findings show that XCR1 and its ligand, lymphotactin, are expressed by oral epithelial cells and suggest that they play a role in regulating the behaviour of these cells.

Amyloidosis: an unusual case of persistent oral ulceration.

We report a case of systemic amyloidosis, with an unusual oral presentation, in a 70-year-old patient suffering from light chain myeloma. The patient presented with extensive ulceration of the tongue and alveolar ridges, and a large swelling in the floor of mouth. Incisional biopsies of the tongue and floor of mouth confirmed amyloid deposition within the tissues with evidence of necrotic ulceration. Amyloid deposition in the oral cavity usually manifests as macroglossia, however it can present elsewhere in the mouth as nodular or plaquelike lesions. Ulceration is a rare finding. This case highlights the variable nature of this condition, and how it can present a challenge to clinicians in terms of diagnosis and treatment.

Synovial sarcoma presenting as a parotid mass: case report and review of literature.

BACKGROUND: Synovial sarcoma is an unusual neoplasm of mesenchymal derivation, which is uncommon in the head and neck sites. In the parotid gland, it is most likely to be misdiagnosed as a myoepithelial, primary mesenchymal, or metastatic neoplasm. METHODS: We report a case of synovial sarcoma in a young woman who was seen with temporomandibular joint symptoms with a 10-year history. A review of the literature was undertaken to highlight the radiologic and histologic features that help in diagnosis as well as the suggested therapeutic protocols most likely to ensure better survival. RESULTS: Radiologic and histologic studies of the parotid mass led to a diagnosis of synovial sarcoma. A total parotidectomy was performed, and the individual remains tumor free at 36 months. CONCLUSIONS: Review of the literature suggests an aggressive long-term outcome for synovial sarcoma and advocates early diagnosis and radical surgical excision for a favorable prognosis.

Low-grade myofibroblastic sarcoma of the tongue.

Low-grade myofibroblastic sarcoma is a neoplasm of atypical myofibroblasts with fibromatoseslike features and a predilection for head and neck sites, including the oral cavity. These lesions have only been characterized in the last 2 decades, and controversies in the concept of neoplastic myofibroblasts still exist. Lack of obvious cytological atypia may result in their being mistaken for reactive fascitislike lesions or fibromatosis and architectural similarities to fibrosarcoma or leiomyosarcoma may complicate the diagnostic process. This paper describes a spindle cell neoplasm in a 40-year-old man that was diagnosed 9 years ago as an unclassifiable myofibroblastic proliferation. The recurrent tumor, which presented 6 years following excision of the original tumor, was subsequently classified as a low-grade myofibroblastic sarcoma. The morphological, immunohistochemical, and electron microscopic features of this unusual sarcoma and the most likely differential diagnoses are discussed.

Leukaemic infiltration of the mandible in a young girl.

BACKGROUND: This report presents a case of leukaemic infiltration of the mandible in a 10-year-old female of Sudanese extraction. CASE REPORT: The patient was in remission from acute lymphoblastic leukaemia when she presented with pain localized to the alveolar ridge overlying the unerupted lower right second permanent molar. Two days later, she developed right inferior alveolar nerve paraesthesia. Radiographic imaging demonstrated cortical line absence around the developing lower right second and third permanent molars, and distal displacement of the lower right third molar. In addition, the cortical outline of the right inferior dental canal lacked clarity. Biopsy confirmed leukaemia recurrence demonstrating the Philadelphia chromosome. Tailored chemotherapy was commenced, and a bone marrow transplant was carried out 12 weeks later. At 6-month dental review, the patient remained exceptionally well with no bone pain and normal sensation in the right lower lip. CONCLUSION: The importance of regular and long-term dental examination of patients with leukaemia is discussed.

Oral cysticercosis.

Cysticercosis is the result of infection with the larval stage of the tapeworm, Taenia solium. The parasite may settle at any site in the body without causing symptoms, which arise almost exclusively from the involvement of brain or eye, and this may occur several years after infection. Cysticercosis is one of the leading causes of acquired epilepsy in Latin America, parts of Asia, and Africa. More cases are being reported in other countries as a result of immigration from endemic areas. Cysticercosis may cause cystic swellings or nodules in the mouth, and these may be the only evidence of the disease. We present a healthy patient who had multiple intraoral cystic swellings that were diagnosed as cysticercosis in a biopsy specimen. Subsequent investigations showed cysticerci in the brain.

The role of histopathological characteristics in distinguishing amalgam-associated oral lichenoid reactions and oral lichen planus.

OBJECTIVES: To identify histological features that distinguish amalgam-associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP). METHODS: Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion. RESULTS: There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases. The sensitivity and specificity for histological diagnosis were 40% and 32% respectively. There were four features that were used most commonly to discriminate between AAOLR and OLP: an inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue. Each was independently predictive of AAOLR or OLP (P < 0.028). CONCLUSIONS: This study confirms the uncertainty of the diagnostic histological differences between AAOLR and OLP. Distinguishing these conditions should not rely on histology alone, but should be based on a synthesis of all available information including history, examination, histopathology and skin patch testing.

Recurrence of a solitary bone cyst of the mandible: case report.

We report a case of a solitary bone cyst in the mandible of an elderly woman who presented with a bilateral radiolucent lesion that caused bony expansion, and which recurred 30 months after enucleation and bone grafting of the cavity.

Presentation of ICAM-1 protein at the cell surface of oral keratinocytes in the presence of adrenomedullin and corticotrophin.

Increasing evidence suggests that adrenomedullin (AM) and corticotrophin (ACTH) are immunomodulatory. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes not only from peripheral blood into inflamed tissues but also into epithelia. We have investigated the effects of AM and ACTH on the expression of ICAM-1 by human oral keratinocytes. The human oral keratinocyte cell line H357 was incubated with either AM or ACTH for up to 8 hrs and ICAM-1 expression was measured by cell surface ELISA. ICAM-1 was up regulated by both peptides and this was attenuated by the adenylyl cyclase inhibitor SQ22,536 and the NF-kappaB inhibitor SN-50. H357 cells constitutively express ICAM-1 mRNA and expression of this gene was significantly modulated by AM and ACTH. Furthermore AM caused translocation of NF-kappaB from the cytoplasm to the nucleus. This is the first report describing up regulation of ICAM-1 in oral keratinocytes by AM and ACTH and the results suggest both cAMP and NF-kappaB may play a role. These results further suggest both peptides may have an immunostimulatory role in oral muocsa and skin.

Stimulation of adhesion molecule expression in human endothelial cells (HUVEC) by adrenomedullin and corticotrophin.

Adrenomedullin (AM) and corticotrophin (ACTH) are both vasoactive peptides produced by a variety of cell types, including endothelial cells. Although AM and ACTH are considered to be important in the control of blood pressure and the response to stress, respectively, their role in inflammation and the immune response has not been clarified. This study shows, with the use of a cell-based ELISA, that AM and ACTH induce cell surface expression of the adhesion molecules E-selectin, VCAM-1, and ICAM-1 on human umbilical vein endothelial cells (HUVEC). Furthermore, this effect appears to be mediated in part via elevation of cAMP, given that both peptides elevate cAMP, the cell-permeable cAMP analog dibutyryl cAMP is able to mimic induction of all three cell adhesion molecules and the effect of AM and ACTH is inhibited by the adenylyl cyclase inhibitor SQ-22536. These findings demonstrate a role for AM and ACTH in the regulation of the immune and inflammatory response.