Ex-vivo confocal laser scanning microscopy (CLSM) offers rapid tissue examination. Current literature shows promising results in the evaluation of non-melanoma skin cancer but little is known about presentation of melanocytic lesions (ML). This study evaluates ML with ex-vivo CLSM in comparison to histology and offers an overview of ex-vivo CLSM characteristics. 31 ML were stained with acridine orange or fluorescein and examined using ex-vivo CLSM (Vivascope2500 ; Lucid Inc; Rochester NY) in reflectance and fluorescence mode. Confocal images were correlated to histopathology. Benign and malignant features of the ML were listed and results were presented. Sensitivity and specificity were calculated using contingency tables. The ML included junctional, compound, dermal, Spitz and dysplastic nevi, as well as various melanoma subtypes. The correlation of the confocal findings with histopathology allowed the identification of different types of ML and differentiation of benign and malignant features. The study offers an overview of confocal characteristics of ML in comparison to histology. Ex-vivo CLSM does not reproduce the typical in-vivo horizontal mosaics but rather reflects the vertical histological presentation. Not all typical in-vivo patterns are detectable here. These findings may help to evaluate the ex-vivo CLSM as an adjunctive tool in the immediate intraoperative diagnosis of ML. Superficial spreading malignant melanoma. Histopathology (H&E stain; 200×) correlated to the reflectance (RM; 830 nm) and fluorescence mode (FM; 488 nm) in the ex-vivo CLSM (Vivablock by VivaScan , acridine orange).

Ex-vivo confocal laser scanning microscopy (CLSM) is an emerging diagnostic tool allowing fast and easy microscopic tissue examination. The first generation of ex-vivo devices have already shown promising results in the ex-vivo evaluation of basal cell carcinoma compared to Mohs surgery. Nevertheless, for the diagnostics of pathological skin lesions the knowledge of normal skin features is essential. Therefore we examined 50 samples of healthy skin from various donor sites including head and neck (n = 25), trunk (n = 10), upper (n = 10) and lower extremities (n = 5) using a new generation ex-vivo CLSM device offering three different laser wavelengths and compared the findings to the corresponding histological sections. In correlation with the histopathology we identified different layers of the epidermis, differentiated keratinocytes from melanocytes and described in detail skin appendages including hair follicle, sebaceous and sweat glands. Furthermore, structures of the dermis and subcutis were illustrated. Additionally, artefacts and pitfalls occurring with the use of ex-vivo CLSM have been documented. The study offers an overview of the main ex-vivo CLSM skin characteristics in comparison to the standard histological examination and helps to recognize and avoid common artefacts. Anatomy of a hair follicle in the reflectance mode (RM) CLSM, fluorescence mode (FM) CLSM and in a routine hematoxylin-eosin stained histological section (H).

Mendelian adult-onset leukodystrophies are a spectrum of rare inherited progressive neurodegenerative disorders affecting the white matter of the central nervous system. Among these, cerebral autosomal dominant and recessive arteriopathy with subcortical infarcts and leukoencephalopathy, cerebroretinal vasculopathy, metachromatic leukodystrophy, hereditary diffuse leukoencephalopathy with spheroids, and vanishing white matter disease present with rapidly progressive dementia as dominant feature and are caused by mutations in NOTCH3, HTRA1, TREX1, ARSA, CSF1R, EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5, respectively. Given the rare incidence of these disorders and the lack of unequivocally diagnostic features, leukodystrophies are frequently misdiagnosed with common sporadic dementing diseases such as Alzheimer's disease (AD), raising the question of whether these overlapping phenotypes may be explained by shared genetic risk factors. To investigate this intriguing hypothesis, we have combined gene expression analysis (1) in 6 different AD mouse strains (APPPS1, HOTASTPM, HETASTPM, TPM, TAS10, and TAU) at 5 different developmental stages (embryo [E15], 2, 4, 8, and 18 months), (2) in APPPS1 primary cortical neurons under stress conditions (oxygen-glucose deprivation) and single-variant–based and single-gene–based (c-alpha test and sequence kernel association test (SKAT)) genetic screening in a cohort composed of 332 Caucasian late-onset AD patients and 676 Caucasian elderly controls. Csf1r was significantly overexpressed (log2FC > 1, adj. p-value < 0.05) in the cortex and hippocampus of aged HOTASTPM mice with extensive Aβ dense-core plaque pathology. We identified 3 likely pathogenic mutations in CSF1R TK domain (p.L868R, p.Q691H, and p.H703Y) in our discovery and validation cohort, composed of 465 AD and mild cognitive impairment (MCI) Caucasian patients from the United Kingdom. Moreover, NOTCH3 was a significant hit in the c-alpha test (adj p-value = 0.01). Adult-onset Mendelian leukodystrophy genes are not common factors implicated in AD. Nevertheless, our study suggests a potential pathogenic link between NOTCH3, CSF1R, and sporadic late-onset AD, which warrants further investigation.

Anal cytology as the solitary screening tool for anal cancer fails to detect anal dysplasia in a considerable number of patients. Additionally, HPV typing and possibly further biomarkers might be applied to identify those patients with a higher risk of developing anal carcinoma, in order to monitor them more closely or directly transfer them to HRA.

Low constitutive N-acetylating capacity has been implicated as a predisposing factor for the development of adverse reactions to certain drugs. This prompted us to investigate whether the N-acetylating capacity of patients with serious cutaneous adverse reactions, i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) differed from that of healthy control subjects. N-acetylating activity was measured in hair root cells by preparing a homogenate from freshly extracted hair roots and assessing acetyl-CoA-dependent N-acetylation by RP-HPLC using 2-aminofluorene as a substrate. Samples were obtained from hospitalized patients suffering from acute SJS and TEN or from healthy controls. All patients with SJS and TEN were found to have a low N-acetylating capacity (0.85 nmol/mg/min compared to 2.21 nmol/mg/min in controls, p < 0.05). Based on these findings, a low constitutive N-acetylating capacity may be one of the predisposing factors for the development of serious cutaneous adverse reactions to drugs that require N-acetylation in these patients.