Value Of Electron Microscopy Research Articles

Value of electron microscopy as perceived by nephrologists in Flanders, Belgium

ABSTRACT Electron microscopy (EM) is an important complementary tool in biopsy diagnosis of kidney disease. However, EM is a costly technique and not universally available. In order to understand nephrologists’ perspectives on EM, a survey among Flemish nephrologists was conducted. The survey explores nephrologists’ knowledge and satisfaction with EM, the barriers in its use, and its role in decision-making. A questionnaire was sent out to Dutch-speaking nephrologists in Belgium (Flanders) via the professional organization NBVN (Nederlandstalige Belgische Vereniging voor Nefrologie). The average satisfaction of EM accessibility in nephrologists, was 4.0 on a scale from 1 (very unsatisfied) to 5 (very satisfied). The main barrier in ordering EM appeared to be the long turnaround time, indicated by 32.5% of nephrologists. The reports were found mostly understandable by 61.0% of the nephrologists. The impact of EM on diagnosis of kidney disease was estimated higher than its impact on the treatment: 24.4% of respondents estimated diagnosis changes in less than 5% of cases, versus 68.3% estimated treatment changes in less than 5% of cases. This study provides key insights into nephrologists’ perception on EM services, revealing high overall satisfaction. However, there is potential for improvement, especially regarding turnaround times.

Reflections on the value of electron microscopy in the study of heterogeneous catalysts.

Electron microscopy (EM) is arguably the single most powerful method of characterizing heterogeneous catalysts. Irrespective of whether they are bulk and multiphasic, or monophasic and monocrystalline, or nanocluster and even single-atom and on a support, their structures in atomic detail can be visualized in two or three dimensions, thanks to high-resolution instruments, with sub-Ångstrom spatial resolutions. Their topography, tomography, phase-purity, composition, as well as the bonding, and valence-states of their constituent atoms and ions and, in favourable circumstances, the short-range and long-range atomic order and dynamics of the catalytically active sites, can all be retrieved by the panoply of variants of modern EM. The latter embrace electron crystallography, rotation and precession electron diffraction, X-ray emission and high-resolution electron energy-loss spectra (EELS). Aberration-corrected (AC) transmission (TEM) and scanning transmission electron microscopy (STEM) have led to a revolution in structure determination. Environmental EM is already playing an increasing role in catalyst characterization, and new advances, involving special cells for the study of solid catalysts in contact with liquid reactants, have recently been deployed.

Value of electron microscopy in establishing the diagnosis of early stage of renal amyloidosis

Value of electron microscopy in establishing the diagnosis of early stage of renal amyloidosis

Tropheryma whipplei infection (Whipple's disease) in a patient after liver transplantation

Whipple's disease (WD) is a rare infection caused by the bacterium Tropheryma whipplei that can affect multiple organs and most commonly occurs in the immunocompetent host. Only 3 cases of WD have been reported in the setting of immunosuppression for organ transplantation. Here, we report the first case of WD, to our knowledge, in a patient after liver transplantation with comorbid graft-versus-host-disease. We discuss the diagnostic challenges in this setting and the value of electron microscopy and insitu hybridization methods for confirming the infection. WD may be under-diagnosed in immunosuppressed transplant patients because the disease can present with atypical clinical and histological features that suggest other conditions.

The value of electron microscopy in the diagnosis of renal disease

In the literature of recent years there are few publications on the importance of research in electron‑microscopic pathomorphological diagnosis of kidney disease. The most important, which is diagnosed only on the basis of these studies are: minimal change disease, assessment of mesangial cell proliferation as well as the differentiation of the types of membranoproliferative glomerulonephritis, fibrillary glomerulonephritis, lupus nephritis, thin basement membrane disease, Alport syndrome, hemolytic‑uremic syndrome. This report presents the most characteristic features of the ultrastructure allowing for diagnosis of these diseases.

The Continuing Value of Ultrastructural Observation in Central Nervous System Neoplasms in Children.

Central nervous system (CNS) neoplasms are the second most common childhood malignancy after leukemia and the most common solid organ neoplasm in children. Diagnostic dilemmas with small specimens from CNS neoplasms are often the result of multifactorial etiologies such as frozen or fixation artifact, biopsy size, or lack of knowledge about rare or unfamiliar entities. Since the late 1950s, ultrastructural examination has been used in the diagnosis of CNS neoplasms, though it has largely been replaced by immunohistochemical and molecular cytogenetic studies. Nowadays, pathologic diagnosis of CNS neoplasms is achieved through intraoperative cytology, light microscopy, immunohistochemistry, and molecular cytogenetic results. However, the utility of electron microscopy (EM) in the final diagnosis of CNS neoplasms and investigation of its pathogenetic origin remains critical. Here, we reviewed the distinguishing ultrastructural features of pediatric CNS neoplasms and emphasize the continuing value of EM in the diagnosis of CNS neoplasms.

Iridium Complexes and Clusters in Dealuminated Zeolite HY: Distribution between Crystalline and Impurity Amorphous Regions

Dealuminated zeolite HY was used to support Ir(CO)2 complexes formed from Ir(CO)2(C5H7O2). Infrared and X-ray absorption spectra and atomic resolution electron microscopy images identify these complexes, and the images and 27Al NMR spectra identify impurity amorphous regions in the zeolite where the iridium is more susceptible to aggregation than in the crystalline regions. The results indicate the value of electron microscopy in characterizing the amorphous impurity regions of zeolites and a significant stability limitation of metals in these regions of zeolite catalyst supports.

Use of Electron Microscopy in Core Biopsy Diagnosis of Oncocytic Renal Tumors

The distinction between oncocytoma and chromophobe renal cell carcinoma, important clinically, may be challenging, especially as the tissue sample size decreases. Ancillary studies can be helpful, although subject to interpretation and sample variability. The aim of this study was to examine the value of electron microscopy in differentiating between oncocytoma and chromophobe renal cell carcinoma on formalin fixed paraffin embedded needle core biopsies. Twenty renal needle core biopsies were evaluated. Despite formalin fixation and paraffin embedding, the classic ultrastructural features of these neoplasms were retained, revealing 80% sensitivity and 100% specificity by initial work-up.

Value of Electron Microscopy in the Diagnosis of Glomerular Diseases

To evaluate the contribution of electron microscopy to the final diagnosis of glomerulopathies, the authors established a prospective study during the first semester of 2006. A total of 52 kidney biopsies were performed with 3 samples for light microscopy, immunofluorescence, and electron microscopy. Among these renal biopsies, only 20 were examined with electron microscopy because the diagnosis made on the basis of conventional methods had remained unclear or doubtful. In 18 cases, electron microscopy was undertaken for the investigation of primary kidney disease. The 2 remaining cases were transplant biopsies. In this series of 20 patients, there were 3 children with an average age of 9 years and 17 adults with an average age of 35.5 years. Fifteen patients (75%) were nephrotic. The study revealed that electron microscopy was essential for diagnosis in 8 cases (40%) and was helpful in 12 cases (60%). In conclusion, the results showed that the ultrastructural study provides essential or helpful information in many cases of glomerular diseases, and therefore electron microscopy should be considered an important tool of diagnostic renal pathology. As was recommended, it is important to reserve renal tissue for ultrastructural study unless electron microscopy can be routinely used in all biopsies. Thus, this technique could be performed wherever a renal biopsy has to be ultrastructurally evaluated.

Origins, Contemporary Applications, and Future of Diagnostic Electron Microscopy Applied to Soft Tissue Tumors

Diagnostic electron microscopy (EM) of soft tissue tumors is discussed. From its beginnings in the 1930s, EM technique has developed to produce uniform results. Similarly, interpretational criteria for tumors have also matured with the accumulation of data over time from several sources—publications from pathology journals (the 1960s to 1980s especially), histology textbooks, edited series, monographs, and CDROM material. Although EM is less popular than immunohistochemistry, many pathologists still value it, especially in soft tissue tumors, which, being uncommon, can be more diagnostically challenging. EM is useful in increasing diagnostic confidence, protecting against litigation, providing continuing education for pathologists, contributing to academic knowledge and research, and providing material for teaching. It refines diagnoses by clarifying uncertainties arising from clinical and light microscopy inconsistencies, which include those due to limitations of immunohistochemistry. Selected cases are described illustrating the value of EM. Here, completely unexpected neuroendocrine granules were observed in an extraskeletal myxoid chondrosarcoma; collagen secretion granules with prominent rER were crucial for the diagnosis of sclerosing epithelioid fibrosarcoma in a tumor lacking an agreed diagnosis by light microscopy; whereas in 2 spindle-cell neoplasms, EM was able to discriminate between myofibroblastic sarcoma and leiomyosarcoma on the basis of cell surface features (fibronexus and lamina). The use of EM in the future will depend on demonstrating continued diagnostic utility, but also, it is hoped, on recognizing this technique as a valid component in the multidisciplinary analysis of tumors, to better understand their cell biology, and ultimately help patients.

Role of Electron Microscopy in the Diagnosis of Ocular Mucous Membrane Pemphigoid

To evaluate the role of electron microscopy (EM) for the diagnosis of ocular mucous membrane pemphigoid (MMP) among patients with cicatrizing conjunctivitis. Retrospective case series. One hundred twenty-eight patients with cicatrizing conjunctivitis referred for the evaluation of possible ocular MMP between January 1985 and February 2002 who underwent conjunctival biopsy and evaluation with EM and direct immunofluorescent (DIF) techniques. The diagnosis of each patient was based on DIF techniques. The reproducibility of EM readings was measured by assessing intraobserver and interobserver variability. The diagnosis from EM was compared to the DIF diagnosis from the same patient to evaluate the validity of the EM diagnosis. Sensitivity, specificity, positive predictive value, and negative predictive value of EM for diagnosing ocular MMP. One hundred twenty-six of 128 conjunctival biopsies were available for evaluation of EM findings. The percent agreement between 2 readings from the same observer was 92%, and the percent agreement between 2 independent observers was 78%. The sensitivity and specificity of EM for the diagnosis of ocular MMP were 51% and 72%, respectively. The positive predictive value of EM for the diagnosis of ocular MMP was 49%. The reproducibility of EM findings was good as indicated by high percent agreement for both intraobserver and interobserver measurements. However, the sensitivity, specificity, and positive predictive value of EM for the diagnosis of ocular MMP was low. It seems that EM has limited usefulness in the diagnosis of ocular MMP.

Value of Electron Microscopy in Kidney Biopsy Diagnosis

Kidney biopsy reports given during 2003 were collected from the authors' pathology database. A total of 111 biopsies were performed. Five tumor samples were not studied with electron microscopy (EM). Of the remaining 106 biopsies, 85 were studied with EM. EM was not performed in 10/24 transplant biopsies, or in 11/82 cases of suspected primary kidney disease. The role of EM was evaluated by grouping the samples in 3 categories: (1) EM was essential for diagnosis, (2) EM contributed to the interpretation and cleared uncertainties, and (3) EM had no influence on the diagnostic process. In transplant biopsies EM influenced the final diagnosis in 86% of cases (category 2). In biopsies performed for primary kidney disease EM was essential for diagnosis in 18.3% clearly contributed in 53.5%, and had no influence on the final diagnosis in 28.2% of cases. The study suggests that the importance of EM has not decreased during the last few years. Because only about 25% of the EM reports did not have any influence on the diagnostic process, it is recommended that kidney biopsy protocols should include EM in all biopsy cases, or at least tissue should be reserved for EM studies of all cases. Because of the influence of EM on the diagnostic process the need for EM in pathology training should be emphasized.

Ultrastructural Identification of Primary Tumor Site from Bone Metastases

The value of electron microscopy is demonstrated by ultrastructural identification of primary tumor site from bone metastases in 2 patients.

The Value of Electron Microscopy in the Diagnosis of IgA Nephropathy

Electron microscopy plays a fundamental role in the evaluation of renal diseases in general. IgA nephropathy represents a heterogeneous disease clinically and morphologically. There are a number of conditions that need to be considered in the differential diagnosis of IgA nephropathy. The renal pathologist must wisely integrate the light microscopic, immunofluorescence, and ultrastructural data when evaluating cases in which IgA nephropathy is a consideration. Electron microscopy can be crucial in providing information either to support a diagnosis of IgA nephropathy or to aid in the diagnosis of one of its mimics.

The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

The main causes of the late dysfunction of renal allografts are chronic rejection and chronic transplant nephropathy. Both are clinicopathologic entities, with a similar clinical presentation, but different histologic appearances. Chronic rejection is characterized by the presence of alloantigen-induced lesions (transplant arteriopathy and transplant glomerulopathy), and chronic transplant nephropathy by nonspecific sclerosing changes. The incidence of transplant arteriopathy and transplant glomerulopathy is relatively low. Electron microscopy (EM) may overcome the limitations in the histologic diagnosis of chronic rejection, because it verifies alloantigen-induced chronic microvasculopathy in the peritubular capillaries (transplant capillaropathy), and identifies transplant glomerulopathy more precisely than does light microscopy. To assess the value of EM in chronic rejection diagnosis, a retrospective search for transplant capillaropathy and transplant glomerulopathy was performed in a consecutive series of 91 biopsies performed ≥6 months after implantation (median: 26 months, range 6–186) and the diagnoses were reclassified on the basis of the ultrastructural findings. The definitions used were: transplant capillaropathy: a peritubular capillary profile with seven or more circumferential basement membrane layers, or at least three profiles with five or six circumferential layers; ultrastructurally verified transplant glomerulopathy: thickening of the capillary wall in at least three loops in consequence of the widening of the subendothelial space by abnormal basement membrane material, and the formation of a new layer(s) of basal lamina; and chronic rejection: the presence of transplant capillaropathy and/or transplant glomerulopathy and/or transplant arteriopathy. Histologically, chronic transplant nephropathy, chronic rejection, chronic cyclosporine nephrotoxicity, glomerulonephritis, acute rejection, “suspicious” for acute rejection, and “others” were diagnosed in 37%, 34%, 21%, 19%, 57%, 30%, and 5% of the specimens, respectively. The results of EM increased the diagnosis of chronic rejection to 69% of the cases, and decreased chronic transplant nephropathy to 15%. The individual incidence of transplant capillaropathy and transplant glomerulopathy was 79% and 57%, respectively, and their cumulative incidence was 92%. Five biopsies exhibited merely transplant arteriopathy. A late dysfunction typically had more than one cause; the most frequent combination was chronic rejection and acute rejection. In conclusion, the EM search for transplant capillaropathy and transplant glomerulopathy doubled the frequency of the diagnosis of chronic rejection. Currently, the evaluation of renal allograft biopsies from recipients with a late dysfunction relies on standard light microscopy. Because light microscopy per se proved to be insensitive in the diagnosis of chronic rejection, incorporation of EM into the evaluation of late dysfunction biopsies is strongly recommended.

Value of Electron Microscopy in the Diagnosis of Childhood Nephrotic Syndrome

The value of the ultrastructural study of the renal biopsy was investigated in a series of pediatric patients with nephrotic syndrome. Forty-eight cases of renal biopsies with clinical data were reviewed and divided into diagnostic groups. The contribution of electron microscopy to the final diagnosis was graded as essential — diagnosis could not be reached without it; supportive — it increased the level of confidence in the final diagnosis; and noncontributory. In this series of renal biopsies from 48 children with nephrotic syndrome resistant or nonresponsive to therapy, the mostfrequent diagnosis was minimal change disease, present in 42%of the patients. The contribution of the electron microscopic study to the final diagnosis was essential in 73%of the series, and was supportive in a further 27%.Therefore, it is concluded that the ultrastructural study was an essential component in the study of the renal biopsy in children with nephrotic syndrome, suggesting that electron microscopy needs to continue to be performed for all these patients.

Diagnostic Value of Electron Microscopy in a Case of Juvenile Neuronal Ceroid Lipofuscinosis

Neuronal ceroid lipofuscinoses (NCLs) represent a large group of inherited neurodegenerative disorders characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The authors present a case of juvenile neuronal ceroid lipofuscinosis in a 7-year-old boy. Ultrastructural examination of a skin biopsy disclosed deposits of curvilinear profiles and fingerprint-like structures in epithelial cells of sweat glands, endothelial cells, peripheral nerve endings, and fibroblasts. These findings allowed specific confirmation of the assumed diagnosis of juvenile neuronal ceroid lipofuscinosis. Due to the genotypic and phenotypic variability within the group of NCLs, the clinical investigation may be long and complicated. With the NCL disorders in mind, an accurate diagnosis based on ultrastructural examination of a skin biopsy may shorten this investigation, thus benefitting the patient.

The use of electron microscopy in the investigation of the ultrastructural morphology of immune thrombocytopenic purpura platelets

Ultrastructural studies have proven useful for the accurate identification and classification of certain lymphoid and hematopoietic disorders; however, the value of electron microscopy in the diagnosis and clinical management of platelet pathology is less well defined. Electron microscopy has been used to evaluate inherited platelet disorders. In these disorders, certain platelet structural defects can be characteristic. Recently, we investigated the ultrastructural morphology and immunogold localization of IgG in platelets from patients with idiopathic thrombocytopenic purpura (ITP). The accelerated platelet destruction of ITP is mediated by antiplatelet autoantibodies directed against platelet surface glycoproteins and by the functional capacity of the reticuloendothelial system. The basic dysregulation that occurs in these patients remains unexplained. Traditionally, laboratory investigation of ITP has focused on the development of serologic assays to measure the autoantibodies. As an alternative investigative approach, determination of the immunomorphologic characteristics of platelet-associated IgG (PAIgG) in ITP platelets may prove useful in the diagnosis or clinical management of patients with ITP. Our results showed that the ultrastructural morphology of ITP platelets is similar to that observed for normal platelets. No structural abnormalities are observed in ITP platelets. Immunogold labeling of IgG within α-granules of ITP platelets is significantly higher than that of normal platelets. Additionally, in some ITP platelets, immunogold labeling is also observed on the platelet surface and within channels of the open-cannalicular system. In comparison, immunogold labeling of these structures in normal platelets, is rare, or absent. In conclusion, electron microscopic studies should contribute to furthering our understanding of this common autoimmune disorder, and may provide possible biological explanations for the increased levels of PAIgG in platelets from patients with ITP.

The Diagnostic Value of Electron Microscopy in Human Immunodeficiency Virus-Positive Patients with Gastrointestinal Disease

Background: Our aim was to determine the diagnostic value of electron microscopy in evaluating the etiology of gastrointestinal disease in patients infected with the human immunodeficiency virus (HIV). Methods: A retrospective review of electron microscopic and light microscopic results of all HIV-positive patients with gastrointestinal and liver diseases was made during a 3-year period from June 1995 to June 1998. Results: A total of 145 HIV-positive patients had their electron microscopy specimens reviewed. Of these, 136 were investigated for diarrhea, and the other 9 for increased liver enzymes. Twenty-seven of the 145 (18.6%) HIV-positive patients had a pathogen identified by electron microscopy, compared with only 13 of 145 (9%) identified by light microscopy (P < 0.005). The sensitivity of light microscopy for detecting opportunistic pathogens was 68%. Twenty-one of the 27 (77.8%) patients diagnosed by electron microscopy had microsporidiosis, and the most commonly diagnosed species was Enterocytozoon bieneusi. Light microscopy failed to identify 12 cases of microsporidiosis and 2 cases of leishmaniasis. Conclusions: Electron microscopy contributes substantially to the identification of pathogens in HIV-positive patients. Light microscopy failed to identify one of every two pathogens diagnosed by electron microscopy.

The Continuing Value of Electron Microscopy in Surgical Pathology

For decades, transmission electron microscopy has played a valuable diagnostic role in surgical pathology. The continuing importance of electron microscopy, however, can be debated, given the major advances that have occurred in immunohistochemistry and other techniques. Electron microscopy retains excellent educational potential and broad research applicability, and it continues to be a necessity for the evaluation of a small subset of surgical pathology cases, such as renal biopsies and cilia specimens. The real controversy, then, centers on the contribution of electron microscopy in the evaluation of neoplasms. The opinion of many experts indicates that electron microscopy is still vital in the diagnostic assessment of some neoplasms, and that both electron microscopy and immunohistochemistry are more powerful when viewed as complementary rather than competitive techniques. For electron microscopy to be used to its potential, however, electron microscopists must function effectively as consultants. When optimally applied, electron microscopy remains an essential diagnostic tool.