Thilo Gambichler

Histomorphologic correlation with routine histology and optical coherence tomography

Background: Optical coherence tomography (OCT) is a new and promising diagnostic technique for investigation of skin tumours. We describe a method that makes evaluation and definition of specific morphologic structures of skin tumours via OCT more accurate.

Optical coherence tomography in dermatology: technical and clinical aspects

Optical coherence tomography (OCT), a fairly new non-invasive optical real-time imaging modality, is an emergent in vivo technique, based on the interference (Michelson interferometry) of infrared radiation and living tissues, that allows high-resolution, 2- or 3-dimensional, cross-sectional visualisation of microstructural morphology of tissues. OCT provides depth-resolved images of tissues with resolution up to a few micrometers and depth up to several millimetres depending on tissue type. The investigations using OCT to assess skin structure in clinical settings started in the past decade and consequently proved that this imaging method is useful in visualizing subsurface structures of normal skin, including the epidermis, dermoepidermal junction, dermis, hair follicles, blood vessels and sweat ducts. An increasing number of papers brought evidence of the utility and the precision of OCT technology, in its different technical variants, in diagnosing and monitoring skin disorders, including malignancies and inflammatory conditions, respectively. The present comprehensive review describes and illustrates technical aspects and clinical applications of OCT methods in dermatology.

Anal carcinoma in human immunodeficiency virus-positive men: results of a prospective study from Germany

Background  Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)‐associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM). There is a paucity of data published on the progression of high‐grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma.

Expression of microRNAs in basal cell carcinoma

Background  Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin.

MicroRNAs and the skin: Tiny players in the body's largest organ

MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. Disruption of miRNA metabolism is also involved in wound healing and inflammatory skin conditions. Here, we review the role of miRNAs in cutaneous biology.

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy

Background  Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer‐aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time‐saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer‐aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS).

Combined Treatment with Calcipotriol Ointment and Low-Dose Ultraviolet A1 Phototherapy in Childhood Morphea

Abstract: Various therapies for morphea have been used with limited success, including ones with potentially hazardous side effects. When morphea occurs in childhood it may lead to progressive and long‐lasting induration of the skin and subcutaneous tissue, growth retardation, and muscle atrophy. We report an open prospective study in which the efficacy of a combined treatment with calcipotriol ointment and low‐dose ultraviolet A1 (UVA1) phototherapy in childhood morphea was investigated. Nineteen children (mean age 8.5 years, range 3–13 years) with morphea were exposed to UVA1 (340–400 nm) phototherapy at a dose of 20 J/cm2 four times a week for 10 weeks. Forty phototherapy sessions resulted in a cumulative dose of 800 J/cm2 UVA1. In addition, calcipotriol ointment (0.005%) was applied twice a day. After 10 weeks, palpation and inspection showed a remarkable softening and repigmentation of formerly affected skin resulting in a highly significant (p < 0.001) decrease of the mean clinical score from 7.3 ± 0.9 at the beginning to 2.4 ± 0.9 (relative reduction 67.1%) at the end of combined therapy. Our results indicate that a combined therapy with calcipotriol ointment and low‐dose UVA1 phototherapy is highly effective in childhood morphea. Further controlled studies are necessary to investigate whether this combined therapy is superior to UVA1 phototherapy alone.

Age related changes of human skin investigated with histometric measurements by confocal laser scanning microscopy in vivo

Background/aims: The confocal laser scanning microscope Vivascope (Lucid, Henrietta) allows skin to be studied in real‐time with a resolution of 0.5 µm horizontal and 1.3 µm vertical in vivo. In this study, we present the results of a comparison between the skin of an older and a younger group of volunteers by in vivo histometric measurements.

Differential mRNA Expression of Antimicrobial Peptides and Proteins in Atopic Dermatitis as Compared to Psoriasis Vulgaris and Healthy Skin

Background: Patients with atopic dermatitis (AD) are prone to have skin infections. We aimed to investigate mRNA expression levels of various antimicrobial peptides and proteins (AMPs) in AD patients, and compare it with psoriasis vulgaris (PV) patients and healthy subjects. Methods: Skin biopsies were obtained from healthy subjects and patients with AD and PV. Quantitative real-time RT-PCR was used to determine the mRNA levels of human β-defensin (hBD)-1, hBD-2, hBD-3, LL-37, psoriasin, RNase 7, interferon-γ, and interleukin-10 (IL-10). Results: Except for LL-37, mRNA of hBDs, psoriasin, and RNase 7 was significantly higher expressed in AD (n = 42) and/or PV (n = 35) patients when compared to controls (n = 18). While PV lesions showed significantly higher mRNA hBD-2 levels than lesions of AD, the latter was associated with significantly higher mRNA levels of RNase 7 when compared to PV. A significant positive correlation of hBD expression was observed both in AD patients and PV patients. hBD mRNA levels of AD skin correlated with psoriasin and RNase 7 levels. hBD-1 mRNA expression correlated with AD activity and IL-10 mRNA expression. Conclusions: Most AMPs investigated in this study proved to be overexpressed in AD as well as PV when compared to controls. However, a statistically significant difference in AMP mRNA expression between AD and PV was only found for hBD-2 and RNase 7. A moderate-to-strong linear relationship between the mRNA expression of particular AMPs appears to exist in AD, and to a lesser extent in PV as well.

Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi

Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.