SummaryAndrogenetic alopecia is the most common hair loss disorder, affecting both men and women. Initial signs of androgenetic alopecia usually develop during teenage years leading to progressive hair loss with a pattern distribution. Moreover, its frequency increases with age and affects up to 80 % Caucasian men and 42 % of women. Patients diagnosed with androgenetic alopecia may undergo significant impairment of quality of life. Despite the high prevalence and the variety of therapeutic options available, there have been no national or international evidencebased guidelines for the treatment of androgenetic alopecia in men and women so far. Therefore, the European Dermatology Forum (EDF) initiated a project to develop an evidence-based S3 guideline for the treatment of androgenetic alopecia. Based on a systematic literature research the efficacy of the currently available therapeutic options was assessed and therapeutic recommendations were passed in a consensus conference. The purpose of the guideline is to provide dermatologists as well as general practitioners with an evidence-based tool for choosing an efficacious and safe therapy for patients with androgenetic alopecia. Keywords• alopecia • androgenetic • Therapy • Guideline • hair loss I Introduction to the guideline Needs/problems and issues in patient careAndrogenetic alopecia (AGA) is a common chronic dermatologic disease, affecting both men and women. It is characterized by progressive hair loss usually occurring in a pattern distribution. The frequency increases with age. In Caucasians, at the age of 70 or beyond 80 % of men and up to 42 % of women have signs of androgenetic alopecia. Though the prevalence is high in elderly patients, androgenetic alopecia often already starts at puberty.Independent of age and gender, patients diagnosed with androgenetic alopecia undergo significant impairment in their quality of life. Hair is an important feature of image. Hair loss affects self-esteem, personal attractiveness and may lead to depression and other negative effects of life [1]. Androgenetic alopecia is clearly a burden for both sexes, but it is substantially more distressing for women [2].
The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNAbinding proteins (RBM and DAZ͞SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.
The treatment of female-to-male transsexuals with long-acting testosterone undecanoate may be a feasible and safe option for testosterone augmentation in these subjects. However, monitoring of blood pressure should not be ignored during the treatment, to identify patients liable to develop hypertension.
Background:The detection of V600E BRAF mutations has fundamental clinical consequences as the treatment option with BRAF inhibitors such as vemurafenib or dabrafenib yields response rates of ∼48%. Heterogeneity with respect to BRAF mutation in different metastases has been described in single cases. As this has important implications for the determination of BRAF status and treatment of patients, it is essential to acquire more data.Methods:A total of 300 tumour samples from 187 melanoma patients were analysed for BRAF mutations by pyrosequencing. Equivocal results were confirmed by capillary sequencing. Clinical data with respect to melanoma type, tumour site and survival were summarised for 53 patients with multiple analysed tumour samples (2–13 per patient).Results:BRAF mutations were found in 84 patients (44.9%) and 144 tumour samples (48%) with BRAF mutations in 45.5% of primary tumours and 51.3% of metastases, respectively. In 10 out of 53 patients (18.9%) where multiple samples were analysed results were discordant with respect to mutation findings with wild-type and mutated tumours in the same patient. Mutations did not appear more frequently over the course of disease nor was its occurrence associated with a specific localisation of metastases.Conclusion:As heterogeneity with respect to BRAF mutation status is detected in melanoma patients, subsequent testing of initially wild-type patients can yield different results and thus make BRAF inhibitor therapy accessible. The role of heterogeneity in testing and for clinical response to therapy with a BRAF inhibitor needs to be further investigated.
The human insulin gene enhancer-binding protein islet-1 (ISL1) is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. Recent studies identified ISL1 as a marker for pancreatic well-differentiated neuroendocrine neoplasms. However, little is known about ISL1 expression in pancreatic poorly differentiated and in extrapancreatic well and poorly differentiated neuroendocrine neoplasms. We studied the immunohistochemical expression of ISL1 in 124 neuroendocrine neoplasms. Among pancreatic neuroendocrine neoplasms, 12/13 with poor differentiation were negative, whereas 5/7 with good differentiation but a Ki67 420% were positive. In extrapancreatic neuroendocrine neoplasms, strong positivity was found in Merkel cell carcinomas (25/25), pulmonary small cell neuroendocrine carcinomas (21/23), medullary thyroid carcinomas (9/9), paragangliomas/pheochromocytomas (6/6), adrenal neuroblastomas (8/8) and head and neck neuroendocrine carcinomas (4/5), whereas no or only weak staining was recorded in pulmonary carcinoids (3/15), olfactory neuroblastomas (1/4) and basaloid head and neck squamous cell carcinomas (0/15). ISL1 stained the neuroendocrine carcinoma component of 5/8 composite carcinomas and also normal neuroendocrine cells in the thyroid, adrenal medulla, stomach and colorectum. Poorly differentiated neuroendocrine neoplasms, regardless of their ISL1 expression, were usually TP53 positive. Our results show the almost ubiquitous expression of ISL1 in extrapancreatic poorly differentiated neuroendocrine neoplasms and neuroblastic malignancies and its common loss in pancreatic poorly differentiated neuroendocrine neoplasms. These findings modify the role of ISL1 as a marker for pancreatic neuroendocrine neoplasms and suggest that ISL1 has a broader involvement in differentiation and growth of neuroendocrine neoplasms than has so far been assumed. 995 www.modernpathology.org differentiation in mouse experiments. 8 Apart from its role in the cell line development of the endocrine pancreas, ISL1 was found to have a major role as a marker of cardiac progenitor cell lineage. 9 Recently, ISL1 expression was studied in welldifferentiated pancreatic neuroendocrine neoplasms that are labeled by the WHO as neuroendocrine tumors (NETs). 10,11 In these neoplasms, ISL1 proved to be a good marker for pancreatic NETs and their metastases, with a specificity of 78.4-100% and a sensitivity of 74.3-77.8%. [10][11][12] Neuroendocrine carcinomas of pancreatic and extrapancreatic origin so far have not or only occasionally been tested for ISL1 expression. 12-15 Following our own observation of a strong ISL1 reactivity in a case of a widely metastatic small cell neuroendocrine carcinoma of unknown origin, we launched this study with the aim to test the reliability of ISL1 as a marker for distinguishing pancreatic neuroendocrine carcinomas from their extrapancreatic counterparts and mimics. In addition, we also studied some well-differentiated extrapancreatic neuroendocrine neoplasms such as thyroid ...
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