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Summary: Background: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype‐oriented treatment. The new technique of line‐field confocal OCT (LC‐OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. Aim: To evaluate the main LC‐OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. Methods: In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. Results: Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper‐reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC‐OCT and conventional histology was 90.4% (95% CI 79.0–96.8). Conclusion: LC‐OCT allows noninvasive, real‐time identification of BCCs and their subtypes in vertical, horizontal and three‐dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device. [ABSTRACT FROM AUTHOR]

Background: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non‐invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line‐field confocal optical coherence tomography (LC‐OCT). Methods: Dermoscopy and LC‐OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. Results: Most common LC‐OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC‐OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. Conclusions: Our study describes for the first time specific LC‐OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC‐OCT may open new scenarios in the bedside diagnosis, treatment planning and follow‐up of KC. [ABSTRACT FROM AUTHOR]

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Objectives: Eudaimonic well-being (EWB), increasingly recognized as a critical component of health, typically declines in later life, and there are no existing programs to sustain or increase EWB in older adults. Lighten UP! is an 8-week program to promote EWB through facilitated group sessions in community settings and at-home practice. Building on earlier pilot research, the current study assessed the effect of the Lighten UP! Program using a longitudinal, multi-site design. Methods: Men and women (N = 169) aged 60 and over were recruited from three Wisconsin communities. EWB, life satisfaction, depression, and diverse aspects of health were assessed before and after the program and at 6-month follow up. Results: Participants reported significantly increased EWB; these changes were maintained 6 months later. The specific EWB domains of self-acceptance, positive relations, and personal growth showed the most robust gains. Participants also showed significant and sustained declines in depressive symptoms, anxiety, and hostility. Conclusions: Lighten UP! Program confirmed its positive effects for enhancing EWB in older adults living in multiple community settings. Clinical Implications: Programs that sustain or enhance EWB in older adults can be expected to yield improvements in diverse aspects of mental and physical health. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this review is to summarize studies investigating subjective and psychological well‐being in patients with Parkinson's disease (PD). Materials and Methods: A systematic and integrative review according to PRISMA criteria was performed with a literature search from inception up to September 2017 in multidisciplinary databases (PubMED, Scopus, Web of Knowledge) by combining together key words related to PD and well‐being. Studies were included if: their full‐text was available; they involved PD patients; focused on the selected positive dimensions; written in English. Case studies, conference proceedings, abstract, dissertations, book chapters, validation studies and reviews were excluded. Data extracted from the studies included sample characteristics, the positive dimension investigated, type of measure, study aims, design and results. One reviewer extracted details and commented results with other reviewers. The studies’ quality was assessed following Kmet, Lee, and Cook. Results: Out of 1425 studies extracted, 12 studies (9 quantitative, 2 qualitative, 1 mixed methods) involving 2204 patients with PD were included. Most of the studies had a cross‐sectional design and/or evaluated the effect of physical rehabilitation on well‐being. Articles documented that the illness could impair well‐being for its progressive impact on patients’ motor autonomy. Preserving motor and musculoskeletal functioning facilitate patients’ experience of well‐being, social contribution and the maintenance of their job. Conclusions: Research on positive resources in PD is still scarce compared to other chronic illnesses. The few available investigations suggest the need of preserving motor abilities by proper rehabilitation programs for maintaining and/or promoting patients’ well‐being and life engagement. [ABSTRACT FROM AUTHOR]

Difficult to diagnose and early non-melanoma skin cancer lesions are frequently seen in daily clinical practice. Besides precancerous lesions such as actinic keratosis, basal cell carcinomas (BCCs) score the highest frequency in skin tumors. While infiltrative and nodular BCCs require a surgical treatment with a significant impact on the patients' quality of life, early and superficial BCCs might benefit from numerous conservative treatments, such as topical immune-modulators or photodynamic therapy. Dermoscopy has shown a high sensitivity and specificity in the diagnosis of early BCCs, and non-invasive imaging techniques like reflectance confocal microscopy (RCM) have proven to be helpful. The aim of our study was to investigate the importance of RCM in the diagnosis of BCCs with indistinct clinical and dermoscopic features. We retrospectively examined 27 histologically proven BCCs in which diagnosis was not possible based on naked eye examination; we separately reviewed clinical, dermoscopic, and confocal microscopy features and evaluated the lesions meeting the common diagnostic criteria for BCCs, and our diagnostic confidence. All lesions were clinically unclear, with no characteristic features suggestive for BCC; dermoscopy showed in most cases unspecific teleangiectasias (74 %) and micro-erosions (52 %). Confocal microscopy revealed in most of the cases the presence of specific criteria: peripheral palisading of the nuclei (89 %), clefting (70 %), stromal reaction (70 %), dark silhouettes (70 %), inflammatory particles (70 %), and tumor islands (67 %). In the absence of significant diagnostic clinical signs and with unclear dermoscopic features, specific confocal patterns were present in most of the lesions and enabled a correct diagnosis. In the absence of significant clinical features of BCC and in the case of uncertain dermoscopy, striking confocal features are detectable and easy to recognize in most cases. Confocal microscopy can therefore be instrumentful in the diagnosis of the so-called invisible BCCs. [ABSTRACT FROM AUTHOR]

Background Preliminary studies have described morphological features of basal cell carcinoma ( BCC) imaged by high-definition optical coherence tomography ( HD- OCT) and suggested that this technique may aid in its diagnosis and management. However, systematic studies evaluating the accuracy of HD- OCT for the diagnosis of BCC are lacking. Objective The aim of this study was to identify three-dimensional (3-D) HD- OCT features able i) to distinguish BCC from clinical BCC imitators and ii) to discriminate between the most common BCC subtypes. Based on these particular features, a diagnostic algorithm will be suggested. Method A total of 50 histopathologically confirmed BCCs (18 superficial, 19 nodular, 13 infiltrative) were imaged by HD- OCT at the centre of the lesion prior to standard surgical excision and subsequent histopathological analysis. Fifty images of clinical BCC imitators were also retrieved as a 'pitfalls' group. Results The simultaneous presence of grey/dark subepidermal (hemi-spherical) or intradermal lobulated structure(s) presenting a typical cockade feature in both HD- OCT modes was a significant feature for BCC diagnosis. Features discriminating between BCC subtypes were location of the roof of BCC lobules, vascular pattern of the papillary plexus and stretching effect on the stroma. Clinical BCC imitators such as actinic keratosis, compound and intradermal naevi, amelanotic melanoma, sebaceous hyperplasia and small haemangioma could be differentiated from BCC by means of HD- OCT. Conclusion This study provides a thorough description of 3-D HD- OCT features that can permit discrimination of BCC from clinical BCC imitators and differentiation of BCC subtypes. Based on these features, a diagnostic algorithm is proposed which requires additional validation, but enhances current understanding of the morphological correlates of HD- OCT images in skin. [ABSTRACT FROM AUTHOR]

Background The clinical recognition of lentigo maligna ( LM) and LM melanoma can be very challenging due to the overlapping features it shares with other pigmented macules of the skin. Noninvasive diagnostic techniques can assist in the differential diagnosis. Objectives To identify reflectance confocal microscopy ( RCM) indicators for LM through the identification of in vivo microscopic substrates of the main dermoscopic features seen in flat pigmented lesions of the face. Methods Retrospective analysis of 60 pigmented lesions ( LM, invasive melanoma, solar lentigo/flat seborrhoeic keratosis, lichen planus-like keratosis, pigmented actinic keratosis) was carried out. The main dermoscopic patterns and RCM features were described. A new method for correlating RCM with dermoscopic patterns was developed. Results Pseudonetwork (37 of 60 lesions) and annular granular structures (37 of 60 lesions) were the most frequent dermoscopic patterns, followed by pigmented blotches (27 of 60 lesions). Upon RCM examination, pseudonetwork and blotches differed in melanomas and other nonmelanocytic lesions. These differences included the intraepidermal proliferation of atypical cells (predominantly dendritic-shaped with adnexal tropism) and the presence of a meshwork pattern at the junction. Also, annular granular structures exhibited dendritic cells almost exclusively in melanoma, with no difference between melanomas and nonmelanocytic lesions for the junctional and upper dermal pattern (characterized by dermal inflammation). Fingerprinting was mostly present in nonmelanocytic lesions or corresponded to an overlap with solar lentigo in melanomas. Conclusions RCM is useful for identifying the histological substrate of dermoscopic features in pigmented lesions of the face. It can provide a better definition of the lesion areas, enabling an improved diagnostic approach. [ABSTRACT FROM AUTHOR]

Founder mutations in specific populations are common in several Mendelian disorders. They are shared by apparently unrelated families that inherited them from a common ancestor that existed hundreds to thousands of years ago. They have been proven to impact in molecular diagnostics strategies in specific populations, where they can be assessed as the first screening step and, if positive, avoid further expensive gene scanning. In Lynch syndrome ( LS), a dominantly inherited colorectal cancer disease, more than 50 founder pathogenic mutations have been described so far in the mismatch repair ( MMR) genes ( MLH1, MSH2, MSH6 and PMS2). We here provide a comprehensive summary of the founder mutations found in the MMR genes and an overview of their main characteristics. At a time when high-throughput strategies are being introduced in the molecular diagnostics of cancer, genetic testing for founder mutations can complement next generation sequencing ( NGS) technologies to most efficiently identify MMR gene mutations in any given population. Additionally, special attention is paid to MMR founder mutations with interesting anthropological significance. [ABSTRACT FROM AUTHOR]

Primary and secondary immunodepressive conditions are associated with an increased incidence of sebaceous tumors. Microsatellite instability (MSI) and lack of expression of mismatch repair (MMR) proteins, typical markers of Muir-Torre/Lynch heredo-familial settings, can be recognized also in immunocompromised patients. We aimed to carry on a systematic examination of clinical, immunohistochemical, biomolecular features of sebaceous tumors arising in immunocompromised and immunocompetent patients between 1986 and 2012. Microsatellite screening, immunohistochemical analysis and genetic testing were performed for h MLH1, h MSH2 and h MSH6. Methylation status of MMR genes was checked in cases with immunohistochemistry (IHC) loss of MMR proteins expression and no germline mutations. Fifteen patients had a personal history of visceral carcinomas fulfilling diagnostic criteria for Muir-Torre syndrome. In this cohort, IHC analysis, MSI status and genetic testing were in agreement, showing eight MSH2 and two MLH1 germline mutations. Five patients were immunosuppressed and their sebaceous tumors showed a lack of MSH2/MSH6 expression, although just one case with positive family history for visceral cancer harbored a germline mutation. In immunosuppressed patients, loss of IHC for MMR proteins is not necessarily secondary to MMR germline mutations. IHC false positives are probably due to epigenetic alterations. MSI and lack of expression of MMR proteins can be recognized also in immunocompromised patients without MMR germline mutations. [ABSTRACT FROM AUTHOR]

Trichilemmal cysts (TCs) can occur as sporadic lesions or in hereditary-familial settings with autosomal dominant transmission. These entities have not been widely analyzed in their peculiar aspects yet. The aim of this study was to describe a cohort of patients with diagnosis of TCs through a clinical and biomolecular characterization, intended to highlight some effective diagnostic criteria for their identification. Among 149 cases of this study, 24 cases of TCs (16.1%) arose in patients with at least one first-degree relative with diagnosis of TCs. Peculiar findings concerning hereditary lesions included the multiple presentation with an early onset age. On the basis of clinical evaluation, we propose a panel of clinical and histologic criteria for the diagnosis of hereditary TCs, which includes: (i) the diagnosis of TCs in at least two first-degree relatives or in three first- or second-degree relatives in two consecutive generations; (ii) at least one of the patients with TCs diagnosed <45 years; and (iii) the diagnosis of multiple or giant (>5-cm lesions) or rare histopathologic features (proliferating and ossifying) TCs. [ABSTRACT FROM AUTHOR]

Background. There is increasing literature on the unsatisfactory degree of remission that current therapeutic strategies yield in unipolar depression. The aims of this review were to survey the available literature on residual symptoms of depression, to introduce new targets for therapy and to outline a more stringent definition of recovery.Method. Studies were identified by using MEDLINE (English language articles published from 1967 to June 2006; keywords: recovery, remission, residual symptoms, sequential treatment, drugs and psychotherapy, related to depressive disorder and depression) and a manual search of the literature and Index Medicus for the years 1960-2006.Results. Most patients report residual symptoms despite apparently successful treatment. Residual symptoms upon remission have a strong prognostic value. There appears to be a relationship between residual and prodromal symptomatology. The concept of recovery should involve psychological well-being.Conclusions. Appraisal of subclinical symptomatology in depression has important implications for pathophysiological models of disease and relapse prevention. New therapeutic strategies for improving the level of remission, such as treatment on residual symptoms that progress to become prodromes of relapse, may yield more lasting benefits. [ABSTRACT FROM AUTHOR]

In vivo imaging of Sarcoptes scabiei infestation using line-field confocal optical coherence tomography I Dear Editor, i Scabies remains a worldwide spread disease of considerable health and economic burden with repeated outbreaks in community settings.1 Scabies agent is the ectoparasite I Sarcoptes scabiei i var. I hominis i ; this invisible mite causes a progressive rash, which can be misdiagnosed with eczema or I pruritus sine materia i . Reflectance confocal microscopy (RCM)3 and optical coherence tomography (OCT) were used in the detection of mite infestations (scabies, demodex)4,5 and their therapeutic monitoring.6,7 Line-field confocal optical coherence tomography (LC-OCT, DAMAE Medical®, Paris, France) is new imaging technique that can also be used to visualize mites and related skin changes. [Extracted from the article]

Noninvasive real-time imaging of mite skin infestations with line-field confocal optical coherence tomography Besides reflectance confocal microscopy,1 a new diagnostic imaging device, line-field confocal optical coherence tomography (LC-OCT),2 provides real-time and bedside visualization of I Demodex i (a-c) and scabies mites (d-f) inside human skin. LC-OCT imaging allows quick diagnosis of cutaneous mite infestation and therapeutic follow-up. [Extracted from the article]

The article presents a case study of a 59-year-old white male presented with a 3-weeks history of erythema and oedema of the left hand, and a necrotic ulcer of the left thumb, after a holiday in Greece, associated with extreme pain. Topics include the local erythematous reaction stated to have started after fishing, during which the patient was attacked by a weeverfish.