The diagnosis of nephropathia epidemica (NE) is primarily not histological, but because biopsy samples sometimes reach the pathologist, knowledge of histology may be of diagnostic value, in addition to clarifying the pathogenesis. The authors collected 80 biopsies from 65 patients taken after the onset of NE from various hospital files in Finland. Light microscopic, morphometric, electron microscopic, and immunohistochemical methods were applied in studying these samples. There was slight tubular dilatation and interstitial edema best evidenced during the first month after the onset of the disease. There was limited electron microscopic evidence of endothelial cell damage or reaction, also in the glomeruli. Occasional tubular necrotic cells or mitoses were found. About half of the cases were positive for IgG or IgM, and C3 and fibrin in the tubular basement membrane. Samples of the recovery phase showed interstitial fibrosis. Medullary interstitial hemorrhages were seen in 60% of samples of the first two weeks after onset. Interstitial inflammatory changes were diffuse in the early phases and often focal thereafter. During the first two weeks there was congestion and mild hypercellularity of the glomeruli. There was also slight prominence of mesangium, and evidence of endothelial cell damage or reaction. Osmiophilic glomerular deposits were scanty. Focal immunoglobulin (usually IgG) and complement deposits were present in the glomeruli, but less intense than in classical glomerulonephritis. Without medullary hemorrhages in the biopsy, the suggestive diagnosis could rest on interstitial edema, diffuse but sparse inflammatory infiltrate, dilatation of occasional tubules, changes suggestive of tubular cell death, and congestion and slight hypercellularity of the glomeruli.

Adolescent↗

PubMed1990

[Osteolytic bone lesions, hypercalcemia and malignant lymphoma].

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Adult↗

PubMed1989

Representativity of endomyocardial biopsies: a theoretical approach based on quantitative light microscopy.

To create a model for studying the regional variation in the histologic structure of left ventricular myocardium and the representativity of samples from endomyocardium in predicting the state of myocardium as a whole, 12 human hearts (3 normal and 9 pathological) were investigated with histoquantitative methods. Ten small endomyocardial areas representing biopsy sites (mean area on section 0.94 mm2) were delineated from each heart. The volume fractions of myocardial fibers (VVMY), interstitial space (VVINT) and connective tissue (VVCT) were determined with a point counting method on these areas. Also the mean fiber diameter was measured. The results were compared with the results from three full thickness samples (mean area 3 cm2) from each heart. The values for fiber diameter estimates were almost identical in endomyocardial samples and full thickness samples. On the other hand, VVCT was significantly higher and VVMY lower in endomyocardial samples. The coefficient of variation (10 endomyocardial areas) was 8.3% for fiber diameter, 17.8% for VVMY and 77.5% for VVCT. When estimates of the regional variation within the heart area are available, it is possible to create a model for the prediction of the number of endomyocardial biopsies needed to reach a given accuracy and probability of measurements. The representativity and clinical value of endomyocardial biopsies are discussed on the basis of this statistical approach.

Adult↗

PubMed1989

Morphometric study of human myocardium in acquired valvular diseases.

To study the effect of various valvular heart diseases on the quantitative histology of myocardium, 38 human hearts with valvular lesions were examined (11 aortic stenoses, nine mitral stenoses, nine mitral incompetence and nine combined aortic and mitral valve lesions). The control group consisted of ten hearts without any valvular lesions. With morphometrical methods the volume fractions of myocardial components (myocardial fibres, interstitial space and diffuse connective tissue), the numerical density of arterioles and the mean fibre diameter were estimated. Myocardial fibrosis was more severe in hearts with valvular lesions than in the controls (5.4% vs 3.3%, P less than 0.01), but did not correlate with the anatomical severity of the valvular lesions. The most severe myocardial fibrosis was found in hearts with mitral incompetence (6.7%). Fibre hypertrophy was most severe in hearts with aortic stenosis and in hearts with mitral incompetence (22 microns and 23 microns, respectively). In hearts with severe valvular lesions the mean fibre diameter was 23 microns and in hearts with mild to moderate lesions 19 microns (P less than 0.01). Good correlation was observed between the mean fibre diameter and the weight of the left ventricle (r = 0.81, P less than 0.01). The volume fractions of connective tissue and interstitial space were significantly higher and the volume fraction of myocardial fibres was correspondingly lower in the subendocardium than in the subepicardium in hearts with either pressure overload (aortic stenosis) or volume overload (mitral incompetence). In conclusion, myocardial fibrosis occurs in patients with various valvular lesions, but the severity of the fibrosis does not correlate with the anatomical severity of valvular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Transmural differences in ischaemic heart disease: a quantitative histologic study.

To evaluate the possible transmural differences in the structure of left ventricular myocardium in patients with ischaemic heart disease, 45 human hearts were examined with morphometric methods. There were 10 control hearts, 10 hearts with coronary atherosclerosis but without myocardial infarction, 11 hearts with acute subendocardial infarction and 14 hearts with acute transmural infarction. The following histoquantitative parameters were separately estimated for both subendocardium and subepicardium in each heart: the volume fraction of diffuse connective tissue, the mean fiber diameter and the numerical density of arterioles. Diffuse myocardial fibrosis was more severe in subendocardium in all groups, the highest values were found in hearts with acute subendocardial infarction. In all groups the numerical density of arterioles was higher in subendocardium. The numerical density of arterioles was increased in respect to the controls in both subendocardium and subepicardium in hearts with coronary atherosclerosis without evidence of myocardial infarction and in hearts with acute subendocardial infarction. The possible pathophysiological implications for ischaemic heart disease are discussed on the basis of these results. The results suggest different pathophysiological mechanisms in subendocardial and transmural myocardial infarction. They also suggest that transmural differences should be considered when the findings of endomyocardial biopsies are evaluated.

Adult↗

PubMed1987

Sampling in diagnostic morphometry: the influence of variation sources.

The variation sources relevant to a diagnostic morphometric study were analysed. The influence of each source was estimated in two experiments, performed in systems applying computer assisted interactive morphometry. In the first experiment one observer measured the areas of a large number of nuclei in a section from a grade II transitional cell carcinoma of the bladder. In the second experiment two groups of researchers, from Ancona and Kuopio, measured one field from five different samples of transitional cell tumours (including the case of grade II carcinoma). It turned out that pure interobserver variation was responsible for about a half of the total variation present in the diagnostic system. When the variation characteristics of the diagnostic system had been determined, the number of nuclei that had to be measured to reach a defined level of accuracy could be estimated. Such an estimate was also dependent on the predefined expectancy probability of reaching a correct estimate. The study showed that group morphometry (statistical, investigative morphometry) and diagnostic morphometry must be understood as two different approaches in histopathology. By applying group morphometry, good research results can be gathered with cruder measurements than in diagnostic morphometry. Because investigations in group morphometry are more standardized than in diagnostic morphometry, a larger number of structures has to be measured in diagnostic histopathology for the same level of accuracy.

Analysis of Variance↗

PubMed1987

[Cardiac amyloidosis].

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Age Factors↗

PubMed1987

Application of morphometry in tumor pathology.

The application of morphometry in tumor pathology is discussed, e.g., its use in studying the biology of tumors, in creating tumor classification(s), in creating methods for the identification of a tumor in the diagnostic context, and in characterizing diagnostic histopathology in absolute terms. In traditional subjective diagnostic histopathology, reproducibility can be defined satisfactorily, but the definition of accuracy is ambiguous; in morphometric histopathology, a satisfactory definition is found for both concepts but it may be difficult to separate them in practice. Morphometric histopathology can study parameters measured from sections or parameters derived from the primary measurements through calculations. In the histopathology of tumors, the following parameters have turned out to be specially valuable: densitometric measurements of nuclei, nuclear area, perimeter and form factors, nucleolar parameters, the number of mitotic cells per area, the cellularity, the volume fraction of the epithelium, and parameters associated with the fraction of tumor tissue in the sample. The standard deviation or other moments of the distribution of these measurements can be more relevant than the mean values of the results. This indicates that more attention should be given to sampling rules, which are important in defining the efficiency of the methods. For rational application of morphometric methods, it is very important to make a distinction between group morphometry and diagnostic morphometry. The latter engenders numerous sources of variation (variation in section thickness, variation in tissue processing, variation in the techniques of measurement, interobserver variation, interlaboratory variation, variation due to subjective interpretation, etc.), which are usually better controlled in group morphometry. The influence on morphometric parameters of variation in section thickness and tissue shrinkage during processing are discussed.

Animals↗

PubMed1986

Quantitation of staining for amyloid in histological sections: sources of variation, correlation analysis, and interstain reproducibility.

Five pathologists estimated with point counting the amount of amyloid in heart muscle autopsy samples from 19 patients who suffered from amyloidosis. The serial sections had been stained with 5 different methods. The different variation sources involved in a quantitative study on amyloid and the interstain reproducibility between the results given by these 5 stains were analyzed. The volume fractions of amyloid after different stains were subjected to correlation analysis. In our test system about a third (34%) of the variation was due to the point counting method. Sirius red had the lowest and Congo red the highest variation due to point counting, since Sirius red gave the most intense staining and highest volume fractions for amyloid. The volume fractions were lowest in Congo red. About 40% of the total variation was composed of the field variation. This variation includes the variation due to variation between fields, field selection and subjective intraobserver variation. Sirius red showed the smallest field variation in respect to the total variation. Congo red, on the other hand, had the highest variation. The variation caused by pure interobserver variation is presented by the difference between total variation and the calculated field variation. This was largest with Sirius red and smallest with Congo red. The pure interobserver variation accounted for about 26% of the total variation. The high reproducibility with Sirius stain is most probably due to the high volume fractions of positively stained material after this stain, not to low interobserver variation. Congo red seems to have low interobserver variation. The senior pathologists were more reliable in measuring the amyloid deposits than the junior pathologists as suggested by interstain reproducibility and variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗

PubMed1986

Observer variation in interactive computerized morphometry.

The validity of a test system in morphometric histopathology depends on the variation sources involved. Biological variation is one of the variation sources, but is also the object to be studied with morphometry. We studied the variation sources in interactive computerized morphometry in two test systems involving two different commercially available image analyzers. The measurements were made on nuclei in a microscopic field of 5 transitional cell tumors (papilloma and WHO grade I-III carcinomas) of the urinary bladder. It turned out that different observers selected a variable number of nuclei for measurements, the coefficient of variation (CV) in the number of nuclei being 11-11.5%. Mean CV in nuclear perimeter measurements was 4.4-4.8%, and in nuclear area measurements 8.2-8.6%. The variation in measurements by 1 observer was smaller, the CV values being 2.8% for the number of nuclei, 1.2% for nuclear perimeter, and 2.4% for nuclear area. The results showed that interobserver variation can be considerable in these systems. It is suggested that special sampling rules should be tested with the idea of finding the relevant approach with the smallest interobserver variation.

Carcinoma, Transitional Cell↗

PubMed1985

Reproducibility of morphometric measurements of amyloid after various staining methods.

Four histologic staining methods used for detecting amyloid (Congo red, viewed in both normal and polarized light, Sirius red, Crystal violet and Thioflavine T) were applied to heart muscle autopsy samples from 19 patients who suffered from amyloidosis. The amount of amyloid present was evaluated with morphometry (point counting) by five pathologists, and the interobserver reproducibility and variation of point counting in these staining methods were analyzed. The Sirius red method showed the least variation and was the most suitable stain for demonstrating amyloid with respect to reproducibility. Thioflavine T showed the greatest variation and was the least suitable stain with respect to reproducibility. The range of variation was considerable in all staining methods. The results show that stains differ in their specificity and sensitivity in staining amyloid, observers differ in their interpretation of staining results and certain stains result in more uniform interpretations than do others.

Amyloid↗