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

Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation

Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase in the numbers of midbrain dopaminergic neurons, in conditional Zeb2 (Nestin-Cre based) knockout mice. Therefore, these findings reveal a new mechanism for the regulation of midbrain dopaminergic axon growth during central nervous system development

Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions

The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials

Objective: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. Study Design: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. Results: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. Conclusions: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis

‘Cytology-on-a-chip’ based sensors for monitoring of potentially malignant oral lesions

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. Objective To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. Materials and methods Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new ‘cytology-on-a-chip’ approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. Results Binary “low-risk”/“high-risk” models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity + specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. Conclusions This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum

Dry mouth in children: an under-reported condition?

Dry mouth has a profound effect on the oral environment and alters susceptibility to oral disease. It is well-recognized in adults but affected children may not report symptoms even when severe oral dryness is present, potentially leading to late diagnosis and missed opportunities to prevent caries and other adverse sequelae. This article describes the causes and clinical signs of salivary hypofunction in children and young people and documents some associated emotional and social impacts on patients and their families. It is illustrated by four cases where the underlying diagnoses were 22q11 micro-deletion syndrome, congenital salivary gland aplasia, sarcoidosis and medication-induced. CPD/Clinical Relevance: An awareness of the possible presentations, underlying causes and impacts of dry mouth in children and young people will enable vigilant dental practitioners to diagnose the problem at an earlier stage, so that appropriate enhanced preventive care and additional support can be offered promptly

Lichen Planus in children

Lichen Planus (LP) is a chronic, inflammatory disease of the skin and mucous membranes. It is more frequently seen in the middle-aged and elderly population but can be present in children, although this is relatively rare. This paper describes the presentation and management of lichen planus in children, illustrated by seven cases seen within the Paediatric Dentistry Unit. Dentists should be aware of the condition and understand when referral to a specialist centre is required and the need for multidisciplinary management of complex cases. CPD/Clinical Relevance: Although oral lichen planus is rare in children, it is important that dentists are able to identify its clinical presentation and abnormal changes to the oral mucosa, as well as being aware of possible local and systemic causes of the condition so that reassurance and correct management pathways can be implemented in primary care practice