Superficial fibromas with CTNNB1 mutation.

Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.

[Conventional epiphyseal chondrosarcoma of childhood and adolescence: a case report]. / Konventionelles epiphysäres Chondrosarkom des Kindes- und Jugendalters: ein Fallbericht.

INTRODUCTION: Conventional chondrosarcoma is the second most common primary malignant bone tumor and usually occurs at older adult ages. It is rare in childhood and adolescence. CASE HISTORY: This case report presents the treatment course of a 13-year-old boy with a symptomatic chondrogenic tumor of the right distal femur. Histopathologically, an epiphyseal intermediate-grade chondrosarcoma (G2) was diagnosed. DISCUSSION: Based on the following case, potential radiological and histopathological differential diagnoses, such as chondroblastoma or chondroblastic osteosarcoma, are discussed against the background of current standards in orthopedic oncology.

[Tumors with predominantly adipocytic morphology]. / Tumoren mit prädominant adipozytärer Morphologie.

More than 20% of soft-tissue tumors belong to the group of adipocytic neoplasms. Difficulties may occur in the differential diagnosis of lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas, in the distinction of dedifferentiated liposarcomas from other soft-tissue sarcoma entities and in the detailed subtyping of liposarcomas. Especially in biopsies, the correct diagnosis and grading may be hampered due to limited tissue. Because of the ever-increasing molecular-pathological knowledge of soft-tissue tumors and the rising distribution of molecular diagnostic assays in institutes of pathology, differential diagnosis has been facilitated, as more than 90% of adipocytic tumors carry more or less specific genomic alterations. In the following, the most important subtypes of adipocytic tumors are described morphologically and genomically.

Coherent modulation up to 100 GBd 16QAM using silicon-organic hybrid (SOH) devices.

We demonstrate the generation of higher-order modulation formats using silicon-based inphase/quadrature (IQ) modulators at symbol rates of up to 100 GBd. Our devices exploit the advantages of silicon-organic hybrid (SOH) integration, which combines silicon-on-insulator waveguides with highly efficient organic electro-optic (EO) cladding materials to enable small drive voltages and sub-millimeter device lengths. In our experiments, we use an SOH IQ modulator with a π-voltage of 1.6 V to generate 100 GBd 16QAM signals. This is the first time that the 100 GBd mark is reached with an IQ modulator realized on a semiconductor substrate, leading to a single-polarization line rate of 400 Gbit/s. The peak-to-peak drive voltages amount to 1.5 Vpp, corresponding to an electrical energy dissipation in the modulator of only 25 fJ/bit.

[Ewing sarcomas and Ewing-like sarcomas : New aspects]. / Ewing-Sarkome und Ewing-artige Sarkome : Neue Aspekte.

Sarcomas of the Ewing family of tumors are aggressive neoplasms occurring in bone and soft tissue of mostly children and young adults. Classical Ewing sarcomas are pathognomonically characterized by fusions between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family (FLI1, ERG, ETV1, ETV4 or FEV). Less frequent cases designated as Ewing-like sarcomas show different genetic rearrangements between EWSR1 and non-ETS genes (NFATC2, POU5F1, SMARCA5, PATZ, ZSG, SP3). Moreover, new molecular alterations biologically unrelated to Ewing sarcomas have recently been described in the category of undifferentiated round cell sarcomas including CIC-DUX4 fusions or BCOR alterations, each carrying unique gene expression signatures. In contrast to classical Ewing sarcomas, the morphologic spectrum of these tumor entities is much broader and includes round cell areas as well as spindled and myxoid components. The immunohistochemical profile with inconsistent CD99 positivity makes diagnosis more difficult and requires the use of a broad spectrum of antibodies and elaborate molecular work-up. Further studies for future therapeutic decision making in these newly described round cell sarcomas as well as for molecular subclassification of undifferentiated round cell sarcomas are ongoing.

[Gastrointestinal stromal tumors of the stomach and precursor lesions]. / Gastrointestinale Stromatumoren des Magens und ihre Vorstufen.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract although they are much less frequent than epithelial tumors. In more than 60% of cases they occur in the stomach. Especially small lesions measuring ≤1 cm in diameter, so-called microscopic GIST can occur multifocally, frequently in the proximal stomach wall and sometimes as an incidental finding in a gastrectomy specimen resected for gastric cancer. The multicentricity of GIST alone is not proof of a metastatic behavior or a syndromal or hereditary disease. Multiple sporadic synchronous and metachronous GIST are characterized by different primary mutations mostly in the KIT or PDGFRA genes and are often less aggressive. It is speculative whether a field effect is responsible or whether still unknown GIST-promoting factors may facilitate the development of several independent lesions. If KIT or PDGFRA mutations are lacking, a succinate dehydrogenase (SDH) deficient GIST has to be considered, either hereditary as Carney-Stratakis syndrome or syndromal as part of a Carney triad.

Generation of 64 GBd 4ASK signals using a silicon-organic hybrid modulator at 80°C.

We demonstrate a silicon-organic hybrid (SOH) Mach-Zehnder modulator (MZM) generating four-level amplitude shift keying (4ASK) signals at symbol rates of up to 64 GBd both at room temperature and at an elevated temperature of 80°C. The measured line rate of 128 Gbit/s corresponds to the highest value demonstrated for silicon-based MZM so far. We report bit error ratios of 10-10 (64 GBd BPSK), 10-5 (36 GBd 4ASK), and 4 × 10-3 (64 GBd 4ASK) at room temperature. At 80 °C, the respective bit error ratios are 10-10, 10-4, and 1.3 × 10-2. The high-temperature experiments were performed in regular oxygen-rich ambient atmosphere.

New Short-Lived Isotope

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

48Ca+249Bk fusion reaction leading to element Z = 117: long-lived α-decaying 270Db and discovery of 266Lr.

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

Immunization with Brugia malayi Hsp70 protects mice against Litomosoides sigmodontis challenge infection.

More than 1·5 billion people are at risk of being infected with filarial nematodes worldwide. Therapy and control of transmission are mainly based on mass drug distribution. As these drugs have to be administered annually or biannually and might be loosing their efficacy, a vaccine against filariae is an alternative approach to chemotherapy. In the current study, we have analysed the potential of Brugia malayi heat shock protein 70 (BmHsp70) as a vaccine candidate in a murine helminth infection. Immunization of BALB/c mice with alum-precipitated recombinant BmHsp70 conferred partial protection against subsequent challenge infection with the rodent parasite Litomosoides sigmodontis. Immunization resulted in reduced numbers of larvae in the pleural cavity as well as reduced numbers of circulating microfilariae. Reduced parasite burden was associated with high titres of BmHsp70-specific antibodies and increased production of type I and II cytokines in response to L. sigmodontis antigen and BmHsp70. In summary, the immunization with BmHsp70 induced cellular and humoral immune responses and partially protected against L. sigmodontis in a challenge infection. Therefore, we hypothesize that BmHsp70 might be considered as a potential vaccine candidate for reduction in the incidence of B. malayi infections in future studies.

Absorption engineering of NbN nanowires deposited on silicon nitride nanophotonic circuits.

We investigate the absorption properties of U-shaped niobium nitride (NbN) nanowires atop nanophotonic circuits. Nanowires as narrow as 20nm are realized in direct contact with Si3N4 waveguides and their absorption properties are extracted through balanced measurements. We perform a full characterization of the absorption coefficient in dependence of length, width and separation of the fabricated nanowires, as well as for waveguides with different cross-section and etch depth. Our results show excellent agreement with finite-element analysis simulations for all considered parameters. The experimental data thus allows for optimizing absorption properties of emerging single-photon detectors co-integrated with telecom wavelength optical circuits.

Acute interventional recanalisation of vertebrobasilar stenoses by angioplasty: complications and 12 months follow up.

INTRODUCTION: In acute symptomatic vertebrobasilar artery stenosis, the use of mechanical recanalisation remains controversial. The complication rate of acute interventional recanalisation (aIR) has to be considered, as evidence from randomised trials is lacking. In a single centre retrospective case series, we here describe complications and outcome after aIR. METHODS: We retrospectively assessed aIR in a tertiary care centre and included the following parameters: indication for aIR, national institute of health stroke scale (NIHSS) score on admission, recanalisation by thrombolysis in myocardial infarction score (TIMI) grades, post-interventional complications, mortality, NIHSS and modified Rankin scale at follow-up and rate of restenosis. RESULTS: We identified 14 aIR (14 percutaneous transluminal angioplasty with or without stent implantation in 12 patients; 6/12 with thrombolysis; n = 6 vertebral artery, n = 8 basilar artery; 4 women, mean age 67 years). Mortality was 25 % (3/12) after 7 days and 42 % (5/12) after 12 months. In 12/14, interventions are complete (TIMI 3, 86 %), in 2/14, a partial recanalisation (TIMI 2, 14 %) was achieved. In one case, a peri-interventional fatal intracerebral haemorrhage occurred (1/12, 8 %). At late follow-up (mean 342 days), one re-occlusion (1/7, 14 %) and one recurrent stroke (1/12, 8 %) were observed. CONCLUSIONS: In our single centre series of vertebrobasilar aIR recanalisation rate was high. However, procedural safety and clinical outcome varied considerably. The results of aIR need to be assessed in multicentric registers to define the procedural risk and outcome in the clinical setting.

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study.

BACKGROUND: Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity. PATIENTS AND METHODS: An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m(2)) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m(2)/week) (arm-B) in patients with stage IB-IIB CC after surgery. Primary objective was progression-free survival (PFS). RESULTS: Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2% (95% CI 81.2-93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001). CONCLUSIONS: Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.

Reduction in incidence of Johne's disease associated with implementation of a disease control program in Minnesota demonstration herds.

This prospective longitudinal observational study was conducted to evaluate the effect of a standardized control program on the incidence of Johne's disease in 8 dairy herds in Minnesota. Depending on recruitment year, herds were followed for between 5 and 10 yr. Program compliance was evaluated using a cohort risk assessment score by birth cohort. Fecal samples from cows in study herds were tested annually using bacterial culture to detect Mycobacterium avium ssp. paratuberculosis (MAP), and serum samples from study cows were tested using an ELISA to detect antibodies to MAP. Clinical Johne's disease was also recorded. Cohort risk assessment score decreased along birth cohorts. Depending on the follow-up period in each herd, 5 to 8 birth cohorts were followed to describe changes in time to MAP bacterial culture positivity, serum ELISA positivity, MAP heavy shedding status, and clinical Johne's disease. The analysis of time to bacterial culture positivity, serum ELISA positivity, heavy fecal shedding status, and clinical Johne's disease using a time-dependent Cox regression indicated a reduction of the instantaneous hazard ratio by birth cohorts and by cohort risk score; however, the strength of association between the cohort risk score and each of the 4 disease outcomes decreased over time. The age at which the cows first tested positive for bacterial culture, serum ELISA, and heavy fecal shedding, and the age of the cows at onset of clinical Johne's disease signs remained constant for all birth cohorts. Based on herd risk scores, overall herds complied with the recommended management practices in the program. Results were consistent with a within-herd reduction of Johne's disease transmission, and that reduction was associated with herd-level management practices implemented as part of the control program.

[Reduced vocal cord movement and hypopharyngeal tumor]. / Stimmlippenminderbeweglichkeit und ipsilaterale Raumforderung im Hypopharynx.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western World. It belongs to the low-grade non-Hodgkin lymphomas and is characterized by clonal reproduction of mature small-cell non-functional B-lymphocytes. CLL affects men somewhat more often than women and the average age at onset is over 50 years. In addition to regional lymph node swelling, typical symptoms include hepatosplenomegaly, leukocytosis and skin disorders such as eczema and pruritus. Manifestations in the oropharynx or hypopharynx are rare but should be kept in mind in the differential diagnosis.

Soft tissue sarcoma: from molecular diagnosis to selection of treatment. Pathological diagnosis of soft tissue sarcoma amid molecular biology and targeted therapies.

During the past few years, differential diagnosis of soft tissue tumours has improved due to novel molecular diagnostic tools. Besides a better differentiation between different tumour entities the recognition of specific molecular aberrations may also help to identify novel therapeutic targets. One of the most promising examples of effective molecularly driven treatment is the gastrointestinal stromal tumour. Shortly after the detection of gain-of-function mutations in the type III receptor tyrosine kinases KIT and PDGFRα a targeted treatment with the tyrosine kinase inhibitor imatinib was introduced and became the gold standard in advanced GIST disease. The success of this therapy with response rates of >80% stable disease and partial remission is still unmatched. Since then, many groups aim to identify other potential molecular targets. Genomic and proteomic signatures may pinpoint potential areas of interest for diagnostic tools, prediction of clinical outcome and potential response to therapeutic targets. This article gives an overview of the most important genomic aberrations in sarcomas, their differential diagnosis and the relevance of molecular biology for treatment strategies.

Production and decay of element 114: high cross sections and the new nucleus 277Hs.

The fusion-evaporation reaction 244Pu(48Ca,3-4n){288,289}114 was studied at the new gas-filled recoil separator TASCA. Thirteen correlated decay chains were observed and assigned to the production and decay of {288,289}114. At a compound nucleus excitation energy of E{*}=39.8-43.9 MeV, the 4n evaporation channel cross section was 9.8{-3.1}{+3.9} pb. At E^{*}=36.1-39.5 MeV, that of the 3n evaporation channel was 8.0{-4.5}{+7.4} pb. In one of the 3n evaporation channel decay chains, a previously unobserved α branch in 281Ds was observed (probability to be of random origin from background: 0.1%). This α decay populated the new nucleus 277Hs, which decayed by spontaneous fission after a lifetime of 4.5 ms.

[Molecular pathology of sarcomas. Update on the research group "Molecular Diagnosis of Sarcomas"]. / Molekularpathologie von Sarkomen. Erste Ergebnisse des Sarkomforschungsverbundes KoSar.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

Hektor: the largest highly elongated asteroid.

New observations of Trojan asteroid 624, Hektor, in April 1979 establish that the high amplitude of the rotational light curve of this object is caused by its elongated shape and not by patches of dark and light albedo on opposing hemispheres. These observations confirm that Hektor is a very unusual object and are consistent with the hypothesis that it may be a compound asteroid formed when two Trojans of comparable size fell together-a rare fossilized example of a planetary accretion process.