Plexiform fibrohistiocytic tumor with molecular and cytogenetic analysis

A child with plexiform fibrohistiocytic tumor is presented, in whom a superficial biopsy was misdiagnosed as an inflammatory granuloma. Cytogenetic analysis revealed a 46,X,del(X)(q13)[3]/46,XX[23] karyotype. However, fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (CGH) analysis failed to detect any numerical or quantitative genomic anomaly. Because of lack of specific chromosomal hallmarks, a molecular diagnosis of plexiform fibrohistiocytic tumor with the currently available tools is not reliable.     

Neurofibromatosis--new clinical and molecular genetic aspects]

Neurofibromatosis is not a single entity. Seven types of the disorder are now known, which can be differentiated by clinical and genetic features. The wide variety of clinical manifestations makes close interdisciplinary cooperation necessary, in which the dermatologist frequently has a key role. The most frequent forms are peripheral neurofibromatosis (NF1) and central neurofibromatosis (NF2), for which separate gene localizations have been found on chromosomes 17 and 22, respectively, by molecular genetics techniques. The meanwhile possible prenatal diagnosis raises ethical questions.     

Recent advances in genetic analyses of oculocutaneous albinism types 2 and 4

Patients with OCA are characterized by reduced skin and hair pigmentation and consequent photosensitivity, actinic damage and risk of skin cancer, and by reduced visual acuity and nystagmus. Our survey of Japanese patients revealed that OCA1 was the most frequent type at 34%, while type 2 was present at less than 10%. OCA3 was absent. OCA4, which is a rare type worldwide, was the second most frequent type at 27%. Unexpectedly 10% of the patients turned out to be Hermansky–Pudlak syndrome type 1. Furthermore, the pathogenic p.A481T allele for OCA2, which has 70% melanogenesis activity, was found in approximately 12% of normally pigmented people, indicating that sub-clinical OCA2 might be more frequent in the Japanese than currently thought. And OCA4 is one of the most common types in Japanese patients, despite being rare worldwide.     

蕈样肉芽肿免疫表型分析及分子遗传学研究进展

 蕈样肉芽肿（MF）是最常见的原发皮肤T细胞淋巴瘤,临床上病程缓慢、迁延。MF肿瘤性T细胞最常见的免疫表型是 α/β T辅助细胞表型 (  βF1⁺、TCR-γ^-、CD3⁺、 CD4⁺、CD5⁺、CD8^-、CD45Ro⁺、TIA-1^-),占80%左右。但仍有一部分MF免疫表型很少见,如表达细胞毒性T细胞的标记(  CD8⁺, TIA-1⁺)、表达B细胞的标记（  CD20⁺）、表达间变大细胞的标记（  CD30⁺）、等,这些少见的免疫表型很容易与其它侵袭性较高的淋巴瘤相混淆,造成误诊、误治。本文对MF的免疫表型进行分析总结,并探讨其分子遗传学研究进展。     

Silver-containing dressings and the need for evidence

PURPOSE: To present the practitioner with detailed information on silver-based dressings, including evidence of their efficacy and current practice related to these dressings. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in better understanding the evidence for and current use of silver-based dressings. OBJECTIVES: After reading this article and taking the test, the reader should be able to: 1. Describe the indications, actions, and adverse effects related to silver compounds used in wound care. 2. Review the chemical properties and actions that affect the action of silver compounds. 3. Discuss the limitations of current evidence related to silver-containing dressings, along with some of the rating systems used for evaluating scientific evidence.     

Muir-Torre syndrome: clinical features and molecular genetic analysis

We report a 62-year-old man with rectal cancer, two keratoacanthomas and multiple sebaceous adenomas, epitheliomas and sebaceous hyperplasia. His brother and father died from colorectal cancer. A subgroup of patients with the Muir-Torre syndrome (MTS) is allelic to the cancer family syndrome. This genetic disorder is caused by an autosomal dominant inherited germline mutation in one of the DNA mismatch repair genes. It is thought that a somatic mutation of the other allele leads to a genomic instability responsible for tumorigenesis. In the patient presented here the instability was detected in two characteristic skin lesions; sebaceous adenoma and epithelioma. The search for a causal germline mutation revealed a frameshift mutation in the mismatch repair gene hMSH2 leading to a truncated protein. A presymptomatic molecular diagnosis can be offered to the children of the patient.     

The phenotypic and molecular genetic features of pachyonychia congenita

Pachyonychia congenita (PC) is an autosomal dominant genodermatosis caused by heterozygous mutations in any one of the genes encoding the differentiation-specific keratins K6a, K6b, K16, or K17. The main clinical features of the condition include painful and highly debilitating plantar keratoderma, hypertrophic nail dystrophy, oral leukokeratosis, and a variety of epidermal cysts. Although the condition has previously been subdivided into PC-1 and PC-2 subtypes, the phenotypic characterization of 1,000 mutation-verified PC patients enrolled in the International PC Research Registry, coordinated by the patient advocacy group PC Project, shows that there is considerable overlap between these subtypes. Thus, a new genotypic nomenclature is proposed, in which PC-6a represents a patient carrying a mutation in the K6a gene, etc. Although a rare disorder, PC represents a good model for therapy development, and international efforts are ongoing to develop and deliver siRNA, gene, correction, small molecule, and other strategies to treat this painful, disabling skin condition. The special relationship between PC Project and the PC research community has greatly accelerated the development pathway from gene identification to clinical trials in only a few years and represents a paradigm of hope for other orphan diseases.     

结节性硬化症的分子遗传学研究进展

结节性硬化症(TSC)是一种多系统疾病,主要的特征是脑、皮肤、眼睛、心、肺、肾等器官出现肿瘤样损害,称为错构瘤.它是一种由基因决定的常染色体显性遗传病,由于TSCI或TSC2基因的突变失活引起.近年来,在结节性硬化症的基因研究方面取得了一定进展,对于TSC1、TSC2基因多态性、基因功能及其产物的相互作用有了更加深入的了解,但是仍需要对这种复杂的疾病进行更深入地研究以降低其发病率和死亡率.概述近年来在结节性硬化症的分子遗传学方面取得的新进展.     

Cystic sebaceous tumors as marker lesions for the Muir-Torre syndrome: a histopathologic and molecular genetic study.

Cystic sebaceous tumors (CST) are well-circumscribed, large, deeply located dermal sebaceous proliferations with a cystic growth pattern. We identified 12 CST in 8 of 19 patients with Muir-Torre syndrome (MTS). We interpret CST as a tumor spectrum with clearly benign cystic sebaceous adenomas at one end and proliferative atypical cystic sebaceous tumors at the other. When examining these proliferative atypical tumors on morphologic criteria alone, the possibility of an evolving cystic sebaceous carcinoma cannot be excluded. We have not observed recurrences or metastases, indicating that these lesions are not highly malignant carcinomas. In 10 of 12 cases of CST, we examined microsatellite instability (MSI). All 10 examined examples of CST from patients with MTS showed MSI characteristic for hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by autosomal dominant inherited DNA mismatch repair (MMR) defects. Mutational analysis of the MMR genes hMSH2 and hMLH1 had revealed different germline mutations in the hMSH2 gene in three of six examined patients with MTS with CST. We then found four more CST in patients without a history of internal malignancy. All four CST exhibited MSI. By mutational analysis in one of these patients we identified a truncating germline mutation in the MMR gene hMLH1. We conclude that CST is a marker for the mismatch repair-deficient subtype of MTS with a high risk for later internal malignancies. By recognizing CST, the histopathologist can suggest the great likelihood of MTS to the clinician.     

No evidence for maternal-fetal microchimerism in infantile hemangioma: a molecular genetic investigation

In this study, using the placental origin theory as a basis, we set out to explore whether hemangioma endothelial cells (HEC) were maternal in origin. We rigorously addressed this hypothesis using several molecular genetic techniques. Fluorescent in situ hybridization on surgical specimens of proliferating hemangiomas (n=8) demonstrated no XX-labeled HEC from resected tumors of male infants. This analysis was followed by PCR genotyping of HEC (n=11) using microsatellite markers where cellular components were genotyped and compared to genomic DNA of corresponding mother-child pairs. In the seven informative mother-child pairs, HEC matched the genotype of the child and not the maternal genotype. Concerned that HEC represented a mixed population of cells, we subsequently enriched for cells using the placental-specific endothelial cell (EC) marker, Fc gammaRII. Three informative mother-child pairs exhibited only the genotype of the child in our enriched cell population. Using sequence analysis, we identified an informative single nucleotide polymorphism in an exon of the placental-EC-specific protein, GLUT1. When comparing GLUT1 complementary DNA (cDNA) with mother-child DNA, the genotype of the cDNA matched the constitutional DNA of the child. Our results indicate that hemangiomas are not microchimeric in origin. This study provides further insight into the origin of a tumor whose pathogenesis remains elusive.     

Pityriasis rosea and the need for a serologic test for syphilis

A rapid plasma reagin (RPR) test was performed in fifty patients with a clinical diagnosis of pityriasis rosea to determine the frequency of syphilis as the underlying cause of the eruption. In none of the fifty patients was syphilis the cause. Experience in diagnosing skin diseases, frequency of syphilis in the community served, and the characteristics of the individual eruption are important factors in the decision to perform an RPR test.     

Considerations of the pathogenesis of parakeratosis variegata based on morphologic and molecular genetic findings]

We report on a 63-year-old woman who had been suffering from generalized parakeratosis variegata since she was 7 years old. Increased tightness of the skin was the only clinical symptom. On the whole integument except for the face, we found a fine network of hyper- and depigmentation and telangiectasias. The skin surface was dry and atrophic with fine lamellar scaling. Histological, immunohistological and ultrastructural findings indicated early infiltration by a cutaneous T-cell lymphoma. However, PCR analysis of the T-cell receptor gamma-chain genes revealed multiple amplification products favouring a polyclonal T-cell proliferation. In light of the clinical history over a period of 56 years, we consider parakeratosis variegata to be a benign, chronic inflammatory condition, as is confirmed by the results of PCR analysis in this patient.