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[Application of electron microscopy to tumor diagnosis--observation of 1000 cases with both light and electron microscopy].

We observed 1000 cases human tumors by electron microscope, as compared with by light microscope. Results were classified into four groups: First, the diagnosis by both light microscope and electron microscope were the same in 92 per cent of total cases. Second, diagnosis by light microscope was completely changed by the use of electron microscope, and the correct diagnosis was determined only by electron microscope in 4 percent when light microscope failed. Third, although major diagnosis of some tumors by both light and electron microscope was the same, by electron microscope, the diagnosis was extended and supplemented in 3 per cent. Finally, diagnosis was still unclear in 1 per cent. We think that ultrastructural evaluation contributes to diagnosis in 7 per cent of all the cases. Electron microscope plays a very important role in the differential diagnosis of tumors, especially, small cell malignant tumors, and pleomorphic malignant tumors, and also in determination of two-directional or multi-directional differentiation of some tumors.

Diagnosis, Differential↗

Identification of foreign metallic substances inducing hyperpigmentation of skin: light microscopy, electron microscopy and x-ray energy spectroscopic examination.

Identification of foreign metallic substances that induce hyperpigmentation is now possible with the use of x-ray energy spectroscopy (XES), an ultrastructure, nondestructive technique that allows the correlation of the presence of foreign substances with localized tissue and cellular histological changes. This new analytic technique will be an innovative adjunctive technique in the practice of diagnostic pathology and dermatopathology. It is certain that further evaluation of hyperpigmentation will allow for better identification of possible etiological causes, especially in the evaluation of cutaneous hyperpigmentation secondary to metal toxicity.

Adult↗

Electron microscopy of treponemes subjected to the Treponema pallidum immobilization (TPI) test. II. Immunoelectron microscopy.

The experiments were carried out in order to investigate whether human IgG globulin is absorbed on to the surface of T. pallidum cells during incubation with human syphilis serum in the Treponema pallidum immobilization (TPI) test. Cells of T. pallidum Nichols subjected to the TPI test were further incubated with ferritin conjugated rabbit antihuman IgG globulin. Human IgG globulin could only be demonstrated on immunoimmobilized cells, i.e. cells incubated with human syphilis serum and unheated guinea pig serum (GPS). The surface of the swollen cells was completely covered by a fuzzy layer on to which the ferritin molecules appeared to be attached. In ultrathin sections of cells obtained from the same suspensions the surface of the outer cell membrane was outlined by ferritin molecules. In these cells a rather wide gap was observed between the outer membrane and the cytoplasmic membrane. The ribosomes seemed to have disappeared from the cytoplasm of the immunoimmobilized treponemes, but were present in motile cells obtained from control incubations.

Adsorption↗

The financial and clinical implications of adult malaria diagnosis using microscopy in Kenya.

OBJECTIVE: A recent observational study undertaken at 17 health facilities with microscopy in Kenya revealed that potential benefits of malaria microscopy are not realized because of irrational clinical practices and the low accuracy of routine microscopy. Using these data, we modelled financial and clinical implications of revised clinical practices and improved accuracy of malaria microscopy among adult outpatients under the artemether-lumefantrine (AL) treatment policy for uncomplicated malaria in Kenya. METHODS: The cost of AL, antibiotics and malaria microscopy and the expected number of malaria diagnosis errors were estimated per 1,000 adult outpatients presenting at a facility with microscopy under three scenarios: (1) current clinical practice and accuracy of microscopy (option A), (2) revised clinical practice with current accuracy of microscopy (option B) and (3) revised clinical practice with improved accuracy of microscopy (option C). Revised clinical practice was defined as performing a blood slide for all febrile adults and prescribing antimalarial treatment only for positive results. Improved accuracy of routine microscopy was defined as 90% sensitivity and specificity. In the sensitivity analysis, the implications of changes in the cost of drugs and malaria microscopy and changes in background malaria prevalence were examined for each option. RESULTS: The costs of AL, antibiotics and malaria microscopy decreased from 2,154 dollars under option A to 1,254 dollars under option B and 892 dollars under option C. Of the cost savings from option C, 72% was from changes in clinical practice, while 28% was from improvements in the accuracy of microscopy. Compared with 638 malaria overdiagnosis errors per 1,000 adults under option A, 375 and 548 fewer overdiagnosis errors were estimated, respectively, under options B and C. At the same time, the number of missed malaria diagnoses remained generally low under all options. Sensitivity analysis showed that both options B and C are robust to a wide range of assumptions on the costs of drugs, costs of blood slides and malaria prevalence. CONCLUSIONS: Even with the imperfect microscopy conditions at Kenyan facilities, implementation of revised clinical practice (option B) would substantially reduce the costs and errors from malaria overdiagnosis. Additional interventions to improve the accuracy of microscopy (option C) can achieve further benefits; however, improved microscopy in the absence of revised clinical practice is unlikely to generate significant cost savings. Revision of guidelines to state explicitly age-specific indications for the use and interpretation of malaria microscopy is urgently needed. Further prospective studies are required to evaluate the effectiveness and costs of interventions to improve clinical practice and the accuracy of malaria microscopy.

Adolescent↗

The role of electron microscopy for the diagnosis of glomerulopathies.

CONTEXT: Electron microscopy has been used for the morphological diagnosis of glomerular diseases for more than three decades and its value has been widely emphasized. However, recent reports have analyzed the routine use of electron microscopy critically. Its use in other areas of diagnosis such as tumor diseases has declined considerably; in addition, in view of the unavoidable financial pressure for the reduction of costs due to investigations and diagnostic routines, the selection of cases for electron microscopy has been quite rigorous. OBJECTIVE: To identify the glomerular diseases that depend on electron microscopy for a final diagnosis, by means of reviewing renal biopsies performed over a 12-year period. DESIGN: Prospective SETTING: Hospital Ana Costa, Hospital Guilherme Alvaro and Serviço de Anatomia Patológica de Santos, Santos, São Paulo, Brazil. PARTICIPANTS: 200 consecutive renal biopsies obtained from private hospitals and the teaching hospital from 1979 to 1991 were studied. MAIN MEASUREMENTS: All cases were analyzed via light microscopy, immunofluorescence and electron microscopy. The diagnosis was first made via light microscopy plus immunofluorescence and then via electron microscopy. RESULTS: Electron microscopy was diagnostic or essential for diagnosis in 10.0% of the cases, corresponding to 3.4% of primary glomerulopathies and 100% of hereditary glomerulopathies. Electron microscopy was contributory (useful) to the diagnosis in 5.5% of the cases, confirming the preliminary diagnosis formulated on the basis of clinical and laboratory data and light microscopy plus immunofluorescence findings. We obtained a 7.5% rate of discordant immunofluorescence, which was considered as such when negative immunofluorescence findings were not confirmed by electron microscopy. The final diagnosis with the use of light microscopy plus immunofluorescence alone was 77.0%. CONCLUSIONS: It was possible to diagnose with certainty a great percentage of glomerulopathies (82.5-90% of the cases) based on the light microscopy and immunofluorescence findings alone. Electron microscopy was essential for the diagnosis of hereditary nephropathies.

Biopsy, Needle↗

A reevaluation of routine electron microscopy in the examination of native renal biopsies.

Electron microscopy is routinely utilized in most centers in the evaluation of native renal biopsies. Several studies, primarily from the 1960s and early 1970s, provide justification for its use. Conducted by Siegel et al. (1), the largest study evaluated 213 consecutive renal biopsies and found that electron microscopy was needed for a correct diagnosis in 11%, as well as for confirmation or additional information in another 36%. However, nearly all of these studies were conducted before the use of immunofluorescence in renal biopsy diagnosis became widespread and before several new glomerular diseases and variants were described. In light of this situation and the expense of the procedure, the routine use of electron microscopy in native renal biopsies also examined by immunofluorescence and routine light microscopy was reevaluated. From January 1996 to June 1996, 288 native renal biopsies were received, and all were evaluated by the same pathologist. Of those, 233 met criteria for inclusion in this study, which were > or = 5 glomeruli for light microscopy, > or = 2 for immunofluorescence, and > or = 1 for electron microscopy, not including globally scarred glomeruli. Light microscopy (hematoxylin and eosin, periodic acid-Schiff stains) and immunofluorescence--for immunoglobulin (Ig) G, IgA, IgM, C3, C1q, fibrinogen; kappa/lambda when needed--were evaluated on each biopsy within 48 h of receipt, and a preliminary diagnosis was recorded if possible. Electron microscopy was then performed, and a final diagnosis was made. In 50 cases (21%), electron microscopy was needed to make the final diagnosis; in two of these cases, the preliminary diagnosis was incorrect, and in 48, a firm preliminary diagnosis could not be made. In the other cases, the preliminary diagnosis was correct, but in 48 (21%), ultrastructural study was felt to provide important confirmatory data, and in eight cases (3%), an additional, unrelated diagnosis was supported by the ultrastructural findings. Diagnoses most frequently requiring electron microscopy included minimal change nephropathy, early diabetic nephropathy, membranous lupus nephritis, membranoproliferative glomerulonephritis, postinfectious glomerulonephritis, thin basement membrane nephropathy (or exclusion of this in cases of otherwise unexplained hematuria), and human immunodeficiency virus-associated nephropathy (or exclusion of it in cases of collapsing glomerulopathy). Common diagnoses usually not requiring electron microscopy included IgA nephropathy, diffuse proliferative lupus nephritis, focal segmental glomerulosclerosis (not collapsing glomerulopathy variant), pauci-immune crescentic glomerulonephritis, acute interstitial nephritis, and amyloid nephropathy. This study confirms that, as was the case 20 to 30 yr ago, electron microscopy provides useful diagnostic information in nearly half of native renal biopsies. If electron microscopy cannot be performed routinely on all such biopsies, it is recommended that tissue for ultrastructural studies be set aside in each case.

Biopsy↗