A Comparative Ultrastructural Study of Chondrosarcoma, Chordoid Sarcoma, and Chordoma

A morphologic and electron microscopic study was made of two chordoid sarcomas. These lesions were compared with two classical chondrosarcomas and two chordomas. These chondrosarcoma cells showed many features common to chondrocytes, such as abundant RER, well-developed Golgi complexes, and microvillous cytoplasmatic membranes. The chordoid sarcomas bore a close morphologic resemblance to the chordomas but the ultrastructural features revealed a close relationship to the chondrosarcomas. The chordoid sarcoma and chondrosarcoma cells had scalloped cytoplasmatic membranes, variable amounts of glycogen, round or oval nuclei and microfibrils, collagen, and electron-dense granules in the ground substance. The chordoma was characterized by the presence of stellate and physalipherous cells, as well as many transitional cells, with varying nuclear morphology; dilated and irregular RER in contact with mitochondria and morphologically varied vacuoles are the main features in the cytoplasm. This study suggests that chordoid sarcoma represents a variety of the chondrosarcoma rather than a form of chordoma. These findings also support the suggestion of Weiss that chordoid sarcoma is an extraskeletal myxoid chondrosarcom

Plasma levels of leukotriene B4 during hepatic allograft rejection

At the present time, rejection is the most frequent cause of graft dysfunction in liver transplantation. Differential diagnosis between this and other possible causes of dysfunction—preservation injury, vascular, biliary, viral—may well be difficult, as the clinical and analytical findings are often similar; moreover, no markers specific to rejection are available, and histological studies are necessary for a definitive diagnosis. For this reason, markers indicating activity within the immune system need to be established so as to provide a more specific means of distinguishing rejection from other causes of graft dysfunction. The immune response to an allograft is complex, and the intricate mechanisms regulating it are still not entirely understood. Nevertheless, several specialists have drawn connections among changes in the lymphocyte subpopulations, rises in the interleukin-2 levels, expression of the interleukin-2 receptor, and alteration in the expression of antigens belonging to class II in the greater complex of histocompatibility, with rejection of the allograft. Leukotriene B4 (LTB4) is a derivative of the metabolism of arachidonic acid via 5- lipoxygenase, whose in vitro behaviour is to encourage rejection by favoring leukocyte aggregation, proliferation of T lymphocytes, interleukin-1 and -2 secretion, and the development of "natural killer" cell subpopulations. This study examines the role of LTB4 in mediating the immune response to the hepatic allograft in order to assess its usefulness in early diagnosis of rejection

Leukotriene C4 detection as an early graft function marker in liver transplantation

Leukotrienes are a group of compounds belonging to the eicosanoid family that are formed from the metabolism of arachidonic acid by means of 5-lipoxigenase. Leukotriene C4 (LTC4) has a pronounced proinflammatory character and is formed by combining leukotriene A4 with glutation. This step is catalyzed mainly by the isoenzyme 4-4 of the hepatic glutation transferases, although other enzymes may participate in its formation. The liver plays a decisive part in the formation of this compound despite the fact that it can be synthesized along other cellular lines. In orthotopic liver transplant (OLT), the evaluation of the early functioning of the graft is, in many cases, complex. The difficulty of evaluation lies in the absence of specific markers to indicate when the transplanted organ will prove viable notwithstanding the damage resulting from preservation, and when these lesions are irreversible. The aim of this study is to determine whether there is a relationship between the ability to synthesize LTC4 immediately after OLT and the early functioning of the graft

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

The funding source (British Heart Foundation and UK National Institute for Health Research) provided salaries for research training (FZ, TT, DS, SW), but had no role in study design, collection, analysis, interpretation, writing, or decisions with regard to publication. This work was undertaken at University College London Hospital, which received a proportion of funding from the UK Department of Health National Institute for Health Research Biomedical Research Centres funding scheme. We are grateful to King’s College London Laboratories for processing the collagen biomarker panel

Clinical Utilities of Peripheral Blood Gene Expression Profiling in the Management of Cardiac Transplant Patients

Cardiac allografts induce host immune responses that lead to endomyocardial tissue injury and progressive graft dysfunction. Inflammatory cell infiltration and myocyte damage characterize acute cellular rejection (ACR) that presents episodically in either a subclinical or symptom-associated manner. Sampling of the endomyocardium by transvenous biopsy enables pathologic grading using light microscopic criteria to distinguish severity based on the focality or diffuseness of inflammation and associated myocyte injury. Monitoring for ACR utilizes endomyocardial biopsy in conjunction with history and physical examination and assessment of allograft function by echocardiography. However, procedural and interpretive issues limit the diagnostic certainty provided by endomyocardial biopsy. The dynamic profiling of genes expressed by peripheral blood mononuclear cells (PBMCs) enables quantitative assessments of intracellular mRNA whose levels fluctuate during systemic alloimmune responses. Gene expression profiling of PBMCs using a multi-gene ACR classifier enables the AlloMap® molecular expression test to distinguish moderate to severe ACR (p = 0.0018) in heart transplant patients. The AlloMap test provides molecular insights into a patient's risk for ACR by distilling the aggregate expression levels of its informative genes into a single score on a scale of 0 to 40. The selection of a score as a threshold value for clinical decision-making is based on its associated negative predictive value (NPV), which ranges from 98 to 99% for values in three post-transplant periods: >2 to ≤6 months, > 6to ≤ 12 months, and >12 months. Scores below the threshold value rule out ACR, while those above suggest increased ACR risk. Incorporating the AlloMap test into immunomonitoring protocols provides an opportunity for clinicians to enhance patient care and to define its role in immunodiagnostic strategies to optimize the clinical outcomes of heart transplant recipients. This summary highlights the concepts presented in an invited presentation at a conference focused on Immunodiagnostics and Immunomonitoring: From Research to Clinic, in San Diego, CA on November 7, 2006

Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour

Abstract Background Liposarcoma is an extremely rare primary bone sarcoma. Case presentation We report a case of primary pleomorphic liposarcoma that arose in an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly isointense on T1- and high-signal on T2-weighted sequences with focal areas of increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right distal femur and multiple small pulmonary metastases. Histologically, the tumour was a pleomorphic liposarcoma containing large tumour cells with vacuolated cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in extensive (> 95%) necrosis in the primary tumour and almost complete resolution of the femoral and pulmonary metastases. Conclusions Pleomorphic liposarcoma can present as a sclerotic primary malignant bone tumour; markers of adipose differentiation are useful in histological diagnosis and neoadjuvant MAP chemotherapy results in significant tumor necrosis