The DOG in the Internet. Resources and interest in it

Objective: The German Ophthalmologic Society is rising to the challenges of the information age by offering comprehensive information resources online. Methods: The society's board decided on the development of an Internet website in October 1996. Since February 1997, the website has been available under the Internet address www.dog.org. The amount of information offered has been growing fast during the following 12 months. Results: On its website, the DOG offers information about itself, membership, further education, and a catalog of important addresses, patient information, official recommendations, and the program and abstracts of the annual sessions. The ICD10-aug was integrated into the website as a database application. A discussion group is reserved for ophthalmologists who can use this platform to share ideas and discuss clinical topics. Conclusions: The website of the DOG consists of over 4,900 files that represent the activities of the society. The website's access log indicates steady interest in the information offered. Over 53,000 users visited the DOG website. The discussion group is used by 71 members from 10 countries (all numbers as of 9/98).      

DOG1在胃肠道间质瘤中的表达及意义

目的:探讨DOG1蛋白在胃肠道间质瘤(GISTs)中的表达及意义。方法:在光镜下观察GISTs的组织学特点,并采用免疫组化EnVision法检测DOG1在65例GISTs中的表达。结果:48例肿瘤来源于胃的GISTs中DOG1、CD117、CD34、α-SMA、Des和S-100的表达率分别为89.6%、79.2%、68.8%、33.3%、10.4%、14.6%;17例来源于肠道,其中DOG1、CD117、CD34、α-SMA、Des和S-100的表达率分别为88.2%、64.7%、70.6%、35.3%、11.8%和11.8%。16例CD117阴性的GISTs病例中有13例表达DOG1,7例DOG1阴性的病例中有3例表达CD117。42例(65%)患者随访3~33个月,其中26例病情缓解或无变化,12例肿瘤发生复发或转移,4例死亡。结论:DOG1是诊断GISTs的有用标志物,尤其对CD117阴性的GISTs患者有较高辅助诊断价值。     

DOG1 utility in diagnosing gastrointestinal stromal tumors on fine-needle aspiration

BACKGROUND:

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and the majority contain KIT or PDGFRA activating mutations. Fine‐needle aspiration biopsy (FNAB) is a valuable technique in the diagnosis of GIST and may allow for preoperative therapy with tyrosine kinase inhibitors (TKI). Because of the morphologic diversity of these tumors, routine diagnosis of GIST often relies on C‐Kit immunohistochemical staining in addition to morphologic findings. However, up to 15% of GISTs are C‐Kit negative. Antibodies with increased sensitivity and specificity for detection of C‐Kit–negative GIST cases may be of value, especially because some of these cases may also benefit from TKI therapy.

METHODS:

Immunohistochemical staining for DOG‐1, C‐Kit (CD117) and protein kinase C theta (PKCθ) was performed on FNA cell‐block preparations representing 30 GISTs, 17 leiomyosarcomas, 16 melanomas, 16 schwannomas, 11 adenoid cystic carcinomas, and 8 leiomyomas.

RESULTS:

DOG‐1 was found to have 100% sensitivity and 100% specificity in diagnosis of GIST. C‐Kit demonstrated 70% sensitivity and 76% specificity, and PKCθ showed 40% sensitivity and 86% specificity. When only spindle‐cell neoplasms were considered (adenoid cystic carcinomas excluded), the specificity of C‐Kit increased to 89%. Of interest, all C‐Kit–negative cases showed DOG‐1 positivity.

CONCLUSIONS:

DOG‐1 was the most sensitive and specific of the 3 markers for the diagnosis of GIST in cell‐block preparations and may be of particular use in the diagnosis of C‐Kit–negative GIST. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society     

The Mitochondrial Permeability Transition: Role in Ischemia/Reperfusion Injury

The mitochondrial permeability transition (MPT) occurs when a non-specific pore opens in the inner mitochondrial membrane and converts the mitochondrion from an organelle whose ATP production sustains the normal function of the cell to an instrument of death. Conditions favouring the MPT including high [Ca2+], oxidative stress and adenine nucleotide depletion, all of which occur when a tissue is reperfused following a period of ischemia. Cyclosporin A (CsA) and low pH (<7.0) are potent inhibitors of the MPT. Methods have been devised to demonstrate directly that the MPT pores open upon reperfusion but not during ischemia. The mechanism of the MPT appears to involve binding of mitochondrial cyclophilin (CyP) to the adenine nucleotide translocase (ANT) followed by a calcium-mediated conformational change that converts the ANT into a non-specific pore. Understanding the molecular mechanism has assisted in devising strategies that can be used to protect tissues from damage caused by reperfusion injury. These might also be of benefit in the prevention of multiple organ failure for which reperfusion injury of the gut is thought to be the initial trigger. Protective regimes include the pretreatment of tissues prior to ischemia/reperfusion with CsA (binds to CyP), free radical scavengers that reduce oxidative stress (e.g., pyruvate and propofol) and agents that decrease pHi (e.g., pyruvate or amelioride derivatives). Reperfusion injury can produce both immediate cell death by necrosis or delayed apoptotic cell death and it appears that the mitochondria determine which route is taken. Prolonged opening leads to rapid cell death by necrosis, whilst transient opening leads to cytochrome c release and subsequent apoptosis hours or days later.     

Ultrastructural immunocytochemical study of the dopaminergic innervation of the rat lateral septum with anti-dopamine antibodies

The dopaminergic innervation of the rat lateral septum has been investigated at ultrastructural level by immunocytochemistry using the unlabelled peroxidase-anti-peroxidase method with anti-dopamine antibodies. The specificity of the reaction has been carefully checked by immunological and histochemical controls. A strong immunoreaction was observed in fibres of the lateral septum as well as in their cells of origin in the ventral tegmental area. In the lateral septum, dopamine-immunoreactive fibres were localized in two distinct areas. A first area, located ventrally in the anterior part of the septum was characterized by a high density of immunoreactive varicosities with barely visible intervaricose segments. A more dorsal area, extending throughout the anteroposterior region of the septum, was characterized by immunoreactive fibres in pericellular arrangements. Electron microscopic observations revealed no difference in the ultrastructure of dopamine-immunoreactive profiles in the different areas. Reaction product was found in vesicles, linked to microtubules and in the cytoplasm. Three types of vesicles were seen: (i) small vesicles (30-50 nm) with varying intensity of immunoreaction, filling up the varicosities; (ii) rare large clear vesicles (50-80 nm) with no internal immunoreaction; (iii) very rare large dense vesicles (50-100 nm) with a strong dopamine immunoreactivity. Labelled profiles were observed in clearly defined asymmetrical synaptic contacts with somata and dendrites. Due to the lack of previous work dealing with the use of anti-dopamine antibodies for electron microscope immunocytochemistry, our observations are compared to previous data obtained by more indirect labelling techniques.     

Paraneoplastic focal segmental glomerulosclerosis associated with gastrointestinal stromal tumor with cutaneous metastasis: A case report

BACKGROUNDGastrointestinal stromal tumor (GIST) with cutaneous metastasis is very rare. As a result, cutaneous GISTs have not been well characterized. Focal segmental glomerulosclerosis (FSGS) is also a rare symptom among paraneoplastic nephritic syndromes (PNS). CASE SUMMARYIn this case report, we describe a patient with cutaneous metastatic GIST accompanied by nephrotic syndrome occurring as a malignancy-associated PNS, for whom symptomatic treatment was ineffective, but clinical remission was achieved after surgery. Moreover, the patient has a missense mutation in NPHP4, which can explain the occurrences of GIST and FSGS in this patient and indicates that the association is not random. CONCLUSIONThis is the first reported case of a GIST with cutaneous metastasis accompanied by nephrotic syndrome manifesting as a PNS.     

Immunohistochemistry of soft tissue tumours – review with emphasis on 10 markers

Immunohistochemistry is an integral component in the proper analysis of soft tissue tumours, and a simple panel of six markers is useful in practical triage: CD34, desmin, epithelial membrane antigen (EMA), keratin cocktail AE1/AE3, S100 protein and alpha smooth muscle actin (SMA). These markers frequently assist in the differential diagnosis of fibroblastic, myoid, nerve sheath and perineurial cell tumours, synovial and epithelioid sarcoma and others. However, they all are multispecific, so that one has to be cognizant of their distribution in normal and neoplastic tissues. Four additional useful markers for specific tumour types are discussed here: CD31 and ERG for vascular endothelial tumours, and KIT and DOG1/Ano‐1 for gastrointestinal stromal tumours (GISTs). However, hardly any marker is totally monospecific for any one type of tumour. Furthermore, variably lineage‐specific markers do not usually distinguish between benign and malignant proliferations, so that this distinction has to be made on histological grounds. Immunohistochemical evaluation is most useful, efficient and cost‐effective when used in the context of careful histological evaluation by an experienced pathologist, aware of all diagnostic entities and their histological spectra. Additional diagnostic steps that must be considered in difficult cases include clinicoradiological correlation and additional sampling of remaining wet tissue, if possible.     

A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall

While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987–2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear β-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term ‘seromucinous adenocarcinoma’ is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression.