[Joint tumors: rare but important differential diagnoses of malignant and benign tumors as well as pseudotumors in rheumatology]. / Gelenktumoren: Seltene, aber wichtige Differenzialdiagnosen von malignen und benignen Tumoren sowie Pseudotumoren in der Rheumatologie.

This review article elucidates the differential diagnostics of malignant and benign joint tumors, pseudotumors of the joints and the peri-implant tissue, which are rare but important entities in rheumatology and orthopedic rheumatology. The tissue of origin includes the synovium, peri-implant tissue, peri-articular fibrous tissue and peri-articular osseous tissue. Pseudotumors can be viewed as independent but heterogeneous entities. These are essentially manifested as tumor-like depositions of crystals, calcareous deposits, vascular malformations, ectasia of the synovia and joint capsule tissue and pseudocysts. Other causes for pseudotumors are focal destructive inflammation (e.g. induced by foreign bodies), high grade synovitis and focal fibrinoid necrosis (i.e. rheumatoid nodules). Methodologically, these diagnostics are based on conventional standard staining methods, immunohistochemical analyses of formalin-fixed and paraffin-embedded materials and on molecular diagnostic procedures. The latter are of great importance in cases of benign and malignant joint tumors. The most important immunohistochemical markers with respect to joint tumors are S100, SM-actin, CD68, CD34, STAT6, clusterin, Muc­4, beta-catenin and MDM2-FISH. The following markers are recommended for the differential diagnostics and typing of periarticular tumor metastases in the pathology of rheumatic diseases: AE1/AE3, CK8, p63, TTF­1, TGB, PSA, androgen receptor, GATA, CD56, chromogranin, CDX­2, SAT-B2, SALL4, estrogen and progesterone receptors, CD45LCA, CD30, CD79a and S100. Necrosis, inflammatory infiltrations and reparative inflammatory changes may complicate the histopathological classification. Therefore, a correlation with clinical, microbiological and radiological data in the sense of interdisciplinary synergistic diagnostics may be required.

[Unclear liver lesions in a 19-year-old woman with acute myeloid leukemia]. / Unklare Leberraumforderungen bei einer 19-jährigen Patientin mit akuter myeloischer Leukämie.

A 19-year old woman with acute myeloid leukemia presented with newly observed liver lesions during ongoing consolidation therapy. Due to unexplained cholestasis during induction, biliary duct drainage was performed. Microbiologic and histologic examinations revealed the presence of atypical mycobacteria, namely Mycobacterium abscessus. With an appropriate antiinfective regime which was continuously administered using a portable pump in the outpatient setting, further mycobacterial spread during simultaneous chemotherapy-associated neutropenia was prevented. Despite multiple bacterial resistance mechanisms, proper treatment of leukemia with curative intention could be ensured.

Ewing sarcoma dissemination and response to T-cell therapy in mice assessed by whole-body magnetic resonance imaging.

BACKGROUND: Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease. METHODS: Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human Ewing sarcoma xenografts in mice. In this model, we evaluated the therapeutic efficacy of T cells redirected against the Ewing sarcoma-associated antigen GD2 by chimeric receptor engineering. RESULTS: Of 18 mice receiving intravenous injections of VH-64 Ewing sarcoma cells, all developed disseminated tumour growth detectable by WB-MRI. All mice had lung tumours, and the majority had additional manifestations in the bone, soft tissues, and/or kidney. Sequential scans revealed in vivo growth of tumours. Diffusion-weighted whole-body imaging with background signal suppression effectively visualised Ewing sarcoma growth in extrapulmonary sites. Animals receiving GD2-targeted T-cell therapy had lower numbers of pulmonary tumours than controls, and the median volume of soft tissue tumours at first detection was lower, with a tumour growth delay over time. CONCLUSION: Magnetic resonance imaging reliably visualises disseminated Ewing sarcoma growth in mice. GD2-retargeted T cells can noticeably delay tumour growth and reduce pulmonary Ewing sarcoma manifestations in this aggressive disease model.

[Indications for tissue biopsy. Diagnostic histopathology in rheumatological diseases]. / Biopsieindikationen. Histopathologische Diagnostik in der Rheumatologie.

The role of a standardized histopathological examination of tissue biopsies and of different tissue compartments (synovia, vascular tissue, bone) is discussed in order to stratify the therapy of different forms of arthritis and other rheumatological diseases. Furthermore the diagnostic steps for the histopathological diagnosis of metabolic osteopathic diseases are highlighted. The synovitis-score is described as a diagnostic device leading to the diagnosis of a low-grade synovitis, which is associated with degenerative and posttraumatic arthropathies, or of a high-grade synovitis which is associated with rheumatic diseases.

The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.

BACKGROUND: Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen G(D2) and led us to explore G(D2) immune targeting in this cancer. METHODS: We investigated G(D2) expression in Ewing sarcoma by immunofluorescence staining. We then assessed the antitumour activity of T cells expressing a chimeric antigen receptor specific for G(D2) against Ewing sarcoma in vitro and in vivo. RESULTS: Surface G(D2) was detected in 10 out of 10 Ewing sarcoma cell lines and 3 out of 3 primary cell cultures. Moreover, diagnostic biopsies from 12 of 14 patients had uniform G(D2) expression. T cells specifically modified to express the G(D2)-specific chimeric receptor 14. G2a-28ζ efficiently interacted with Ewing sarcoma cells, resulting in antigen-specific secretion of cytokines. Moreover, chimeric receptor gene-modified T cells from healthy donors and from a patient exerted potent, G(D2)-specific cytolytic responses to allogeneic and autologous Ewing sarcoma, including tumour cells grown as multicellular, anchorage-independent spheres. G(D2)-specific T cells further had activity against Ewing sarcoma xenografts. CONCLUSION: G(D2) surface expression is a characteristic of Ewing sarcomas and provides a suitable target antigen for immunotherapeutic strategies to eradicate micrometastatic cells and prevent relapse in high-risk disease.

On-site infiltration of road runoff using pervious pavements with subjacent infiltration trenches as source control strategy.

The focus in this work was on subsoil infiltration of stormwater from parking lots. With regard to operation, reduced infiltration performance due to clogging and pollutants in seepage, which may contribute to contaminate groundwater, are of interest. The experimental investigation covered a pervious pavement with a subjacent infiltration trench draining an impervious area of 2 ha. In order to consider seasonal effects on the infiltration performance, the hydraulic conductivity was measured tri-monthly during monitoring with a mobile sprinkling unit. To assess natural deposits jointing, road bed, gravel of infiltration trenches and subsoil were analysed prior to commencement of monitoring for heavy metals, polycyclic aromatic and mineral oil type hydrocarbons. Furthermore, from 22 storm events, water samples of rainfall, surface runoff, seepage and ground water were analysed with regard to the above mentioned pollutants. The study showed that the material used for the joints had a major impact on the initial as well as the final infiltration rates. Due to its poor hydraulic conductivity, limestone gravel should not be used as jointing. Furthermore, it is recommended that materials for the infiltration facilities are ensured free of any contaminants prior to construction. Polycyclic aromatic and mineral oil type hydrocarbons were, with the exception of surface runoff, below detection limits. Heavy metal concentrations of groundwater were with the exception of lead (because of high background concentrations), below the permissible limits.

Quantitative CT imaging of the spatio-temporal distribution patterns of vasa vasorum in aortas of apoE-/-/LDL-/- double knockout mice.

OBJECTIVE: To investigate the distribution of vasa vasorum (VV) relative to advanced atherosclerotic lesions (calcified, fibrotic or hemorrhaged) along the aortic wall of apoE-/-/LDL-/- mice at the age of 25 and 80 weeks using high-resolution nano-CT. METHODS: Aortas from male apoE-/-/LDL-/- mice at the age of 25 weeks (n=4) and 80 weeks (n=7) were infused in situ with contrast agent and harvested for scanning with nano-CT. The spatial distribution of vasa vasorum [number and area/cross-section (mm2)] was compared to aortic luminal cross-sectional area and plaque cross-sectional area in the ascending aorta, aortic arch and descending aorta. Results were complemented with co-localized histology. RESULTS: The number and total luminal cross-sectional area of VV showed a significant decrease in the ascending aorta and aortic arch from 25 to 80 weeks but not in the descending aorta. The number and cross-sectional area of VV showed significant local differences depending on whether it was near a fibrotic, and hemorrhaged or calcified plaque in animals at the age of 80 weeks. Area of VV progressively increased along the aorta from least in the ascending aorta

Catabolic properties of microdissected human endosteal bone lining cells.

Bone lining cells cover > 80% of endosteal surfaces of human cancellous bone. Current research assigns to them a dual role: (1) as a biological membrane regulating exchange of substrates between the bone fluid compartment and the extracellular fluid of bone marrow and (2) as a signaling link between the osteocytic network as mechanical receptor and the osteoclastic cell pool for local induction of bone resorption. Furthermore, a catabolic role has been considered. We therefore examined the presence of matrix-metalloproteinases (MMPs) and their physiological tissue inhibitors (TIMPs) as putative proteolytic elements. Firstly, human cancellous bone from 60 patients was examined by immunofluorescence with antibodies against MMPs and TIMPs. Secondly, we applied laser-assisted microdissection (LMD) to isolate bone lining cells from frozen sections of human trabecular bone. mRNA analysis was performed using a single-cell PCR protocol. Three laser microdissection systems were tested: the new generation of Leica LMD and P.A.L.M. laser pressure catapulting (LPC) were compared to P.A.L.M. laser microdissection and micromanipulation (LMM). In a few pooled cell profiles, mRNA of MMP13, MMP14, TIMP1, and CBFA-1 was clearly detected. By immunofluorescence MMP13 and -14 as well as TIMP1 and -2 were strongly present in lining cells, while MMP2, TIMP3, and TIMP4 showed weak or negative signals. Although the functional impact of these enzymatic components remains open, there is additional evidence for a catabolic function of lining cells. The new diode-laser microdissection with LMD and LPC proved to be especially suitable to gain new insights into the properties of bone lining cells.

Paraneoplastic neurological syndromes in patients with carcinoid.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are mainly associated with small-cell lung cancer, gynaecological tumours and lymphomas. Few studies report the association of neurological syndromes with a carcinoid, the majority being a serotonin-related myopathy. We report four patients with a PNS associated with carcinoid. PATIENTS AND RESULTS: The clinical syndromes were sensory neuropathy, limbic encephalitis, myelopathy and brain stem encephalitis. Two patients had antineuronal autoantibodies (one anti-Hu, one anti-Yo), one patient had antinuclear antibodies, and one patient had no autoantibodies. For two of the carcinoids, expression of HuD in the tumour could be demonstrated. CONCLUSION: This study demonstrates that carcinoids can also be associated with classical antineuronal antibody-associated PNS.

Storm water runoff concentration matrix for urban areas.

The infrastructure (roads, sidewalk, commercial and residential structures) added during the land development and urbanisation process is designed to collect precipitation and convey it out of the watershed, typically in existing surface water channels, such as streams and rivers. The quality of surface water, seepage water and ground water is influenced by pollutants that collect on impervious surfaces and that are carried by urban storm water runoff. Heavy metals, e.g. lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), polycyclic aromatic hydrocarbons (PAH), mineral oil hydrocarbons (MOH) and readily soluble salts in runoff, contribute to the degradation of water. An intensive literature search on the distribution and concentration of the surface-dependent runoff water has been compiled. Concentration variations of several pollutants derived from different surfaces have been averaged. More than 300 references providing about 1300 data for different pollutants culminate in a representative concentration matrix consisting of medians and extreme values. This matrix can be applied to long-term valuations and numerical modelling of storm water treatment facilities.

Development and investigation of a pollution control pit for treatment of stormwater from metal roofs and traffic areas.

Source control by on-site retention and infiltration of stormwater is a sustainable and proven alternative to classical drainage methods. Unfortunately, sedimentary particles and pollutants from drained surfaces cause clogging and endanger soil and groundwater during long-term operation of infiltration devices. German water authorities recommend the use of infiltration devices, such as swales or swale-trench-systems. Direct infiltration by underground facilities, such as pipes, trenches or sinks, without pretreatment of runoff is generally not permitted. Problems occur with runoff from metal roofs, traffic areas and industrial sites. However, due to site limitations, underground systems are often the only feasible option. To overcome this situation, a pollution control pit was developed with a hydrodynamic separator and a multistage filter made of coated porous concrete. The system treats runoff at source and protects soil, groundwater and receiving waterways. Typically, more than 90% of the pollutants such as sedimentary particles, hydrocarbons and heavy metals can be removed. Filters have been developed to treat even higher polluted stormwater loads from metal roofs and industrial sites. The treatment process is based on sedimentation, filtration, adsorption and chemical precipitation. Sediments are trapped in a special chamber within the pit and can be removed easily. Other pollutants are captured in the concrete filter upstream of the sediment separator chamber. Filters can be easily replaced.

Metal concentrations in soil and seepage water due to infiltration of roof runoff by long term numerical modelling.

The qualitative effects of stormwater infiltration on soil and seepage water are investigated with long term numerical modelling. The retention behaviour of different soils and materials used in infiltration devices is determined with batch and column tests. Results of the laboratory tests are adsorption isotherms which represent input data for numerical transport modelling. The long term simulations are performed with combinations of different solutions (types of roof runoff) and infiltration devices (swale and trench) under different hydrogeological conditions. The presented results contain the infiltration of low polluted roof runoff, runoff from a roof with zinc sheets and from a roof with copper sheets concerning the heavy metals zinc, copper and lead. The increase of concentrations in the infiltration body is high. For the infiltrated water, the results show a migration to groundwater only for the low adsorbing soil.