Biomedical subjects
Publications and source records attributed to V B Zolotarevskiĭ.
The article covers the functional and clinical importance of hepatic fibrosis. Contemporary principles of invasive and non-invasive diagnostics of fibrotic changes are described. The article deals with the main types of fibrosis, chronic hepatic diseases in which they develop, and the most wide-spread systems of semiquantitative evaluation of fibrotic process' morphologic signs.
Clinical and morphological features of chronic hepatitis B (CHB), C (CHC), and B+C (CHB+C) were studied in 283 renal graft recipients. High total bilirubin serum levels were detected significantly more often in CHB and CHB+C patients vs. CHC patients. High ALT activity was noted in 65% of CHB patients and only in 45% of CHC patients (p = 0.003). Stable low activity of hepatitis prevailed in renal recipients; it was noted in 56.7% of CHB patients, 66.2% of CHC patients, and 62% of CHB+C patients. The character of pathomorphological liver changes in chronic viral hepatitis was studied in 53 renal graft recipients using puncture biopsy. Histopathological activity index (HAI, Knodell R.G. et al., 1981) witnessed a more severe liver lesion in CHB vs. CHC and CHB+C. Thus, inflammatory activity in CHB was found to be minimal or low in 13 patients, and moderate or high in 11 patients, whilst a minimal or low activity in CHC or CHB+C was found in 16 and 10 patients, respectively, and a moderate activity was detected only in two and one, respectively (p = 0.016 and 0.024 compared with CHB). Advanced hepatic fibrosis or cirrhosis was significantly more frequent (p = 0.006) in CHB patients (eight out of 24) than in CHC ones (none out of 18). The rate of advanced sclerotic changes in CHB+C was lower (one out of 10 patients) than that in CHB, and similar to CHC. Thus, clinico-morphological manifestations were more prominent in renal graft recipients with CHB vs. CHC.
Granulomatous hepatitis with non-caseous epithelioid-cell granulomas (43 cases, 86%) and non-specific reactive hepatitis (7 cases, 14%) were observed in liver biopsies of 50 patients with sarcoidosis. Three types of granulomas are distinguished: macrophagal, florid and fading epithelioid-cell granulomas which are consequent stages of the granuloma transformation. Fibrosis arises in the macrophagal granuloma, is increasing in both epithelioid-cell granulomas and is ended by a formation of a small scar. Nonspecific liver changes were also found (hydropic and fat hepatocyte degeneration, hypertrophy and proliferation of the stellate reticulo-endotheliocytes, sinuses capillarization, lymphoid-histiocytic infiltration of the intralobular stroma and portal tract, step-like necrosis which are probably induced by the action of the sarcoidosis unknown etiological factor.
Distribution of lectins (PNA, SBA, WGA, and Con A) has been studied in 53 stomach biopsies. Positive lectin reaction in the foveolar epithelium is observed, including dysplastic foci in the apical plasmalemma and in the cytoplasm around the nucleus this corresponding to the Golgi complex. It was mainly the apical plasmalemma of the columnar epithelium in the foci of intestinal metaplasia. Differences in the receptor localization were established in non-complete intestinal metaplasia, hyperplastic polyps and adenomas this depending on the cell type. Carcinoma cells not infrequently had all the plasmalemma stained with granules of the reaction product being distributed through all the cytoplasm. Lectin reactions are more pronounced in carcinomas accumulating mucus. Lectin binding by tumorous cells containing mucus was enhanced after the elimination of sialic acid as a result of the incubation with neuraminidase. Intensity of lectin reactions somewhat differs in various histological forms of stomach cancer.
Macroscopic, histologic and ultrastructural features of an early stomach carcinoma are presented on the basis of literature and the authors' data. Ultrastructural and immunohistochemical data confirm the concept of a common histogenesis of different histologic types of stomach carcinoma, i.e. from reserve cells. Carcinoma, most likely, develops from reserve cells of the foveolate epithelium and metaplastic epithelium of intestinal type (foci of incomplete intestinal metaplasia with sulfomucine secretion). The data are accumulating on the precancerous nature of severe epithelial dysplasia. The development of an early carcinoma from preexisting dysplasia was observed in patients after long follow-up with repeated gastric biopsies.
Two variants of dysplastic hepatocytes are revealed: small and large which are characterized by cell atypia and probably result from the disturbance of regenerative processes. The disturbance of the liver lobule architectonics is also a feature of dysplasia. The degree of hepatocyte dysplasia assessed by morphometric indices (nuclei surface, ratio of ellipticity) and its frequency increase with progression of the pathological process: chronic persistent hepatitis----chronic active hepatitis----liver cirrhosis----hepatocellular carcinoma. More frequent observation of the hepatocyte dysplasia in viral liver conditions (HBsAg in dysplastic hepatocytes) indicates the role of hepatitis B virus in the development of hepatocyte dysplasia. Increase of DNA content and nuclei polymorphism are observed in small and large dysplastic hepatocytes when the degree of dysplasia is increasing, this making these cells closer to cells of hepatocellular carcinoma and favouring the concept of hepatocellular carcinoma development in the foci of dysplastic hepatocytes, particularly in liver cirrhosis.
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Mammographic and morphologic examination was carried out in 136 females bearing microcalcinates in breast tissue. Morphologic examination identified benign tumors (mostly fibrous cysts) in 72.1% and cancer (mostly ductal and lobular carcinoma in situ or initial signs of invasion) in 27.9% of cases. Calcinates occurred mainly in the epithelium and incipient cancer complexes. The analysis of the data showed shape, structure and distinctness of contours of calcinates to be instrumental in differentiating between malignant and benign lesions.
A patient aged 45 suffering from Whipple's disease is described. The disease has been diagnosed on the basis of morphologic examination of a biopsy specimen of the small intestine mesenteric lymph node. The patient had suffered from the disease for 14 years; during the last 6 months he developed symptoms of the malabsorption syndrome with diarrhea and steatorrhea. The lymph nodes contained numerous macrophages with PAS-positive glycoprotein granules in the cytoplasm, small cavities filled with lipids; electron microscopy has revealed bacillus-like bodies in the macrophages and outside the cells. After the disease has been diagnosed, the patient has been administered a course of tetracycline therapy, that resulted in an improvement of his status.
Mild to severe dysplasia ranked first among precancerous lesions in gastric adenoma and stomach stump gastritis. Repeated gastric biopsy of adenomas revealed enhancement of dysplasia proceeding to papillary adenocarcinoma. Epithelial dysplasia invariably occurred in areas adjacent to early carcinoma. A relationship was established between the pattern of dysplasia and histologic type of cancer. As dysplasia advanced, the ultrastructural signs of cell atypia became more pronounced. The electron microscopic features of severe dysplasia were similar to those of carcinoma.
The results of histological study of material from sectoral resection of 285 mammary glands (MG) from 265 patients with fibrocystic disease (FCD) are presented. 112 cases of a nonproliferative FCD and 173 cases with different variants and degree of proliferation and atypia of the duct and lobules epithelium are recorded. Slight proliferation is observed in 66 cases, mild in 43 cases, pronounced proliferation corresponding to the atypical hyperplasia according to the WHO classification of MG tumours (1981) is found in 30 cases; ductal and lobular carcinoma in situ is observed in 16 cases. A long-term follow-up showed the invasive MG carcinoma in the preserved part of MG to develop in 3 of 172 FCD cases (1.7%). A frequent combination of the atypical hyperplasia foci with an intraductal and lobular carcinoma in situ, revealed in 60 cases of the MG small carcinoma (from 3 to 10 mm in size) with a focal invasion, is in favour of the morphogenetic link between dysplasia and MG carcinoma. Electron-microscopic examination of a proliferative FCD (12 observations) and invasive carcinoma (15 observations) established an enhancement of the specific ultrastructural differentiation in parallel with an increase of the epithelial proliferation but did not reveal the ultrastructural signs of malignant transformation.
A total of 255 gastric carcinomas removed during operations have been examined histologically. Adenocarcinoma and undifferentiated carcinoma were found to be rather stable varieties of gastric carcinoma. Goblet-cell carcinoma is to be considered as a variety of undifferentiated carcinoma. The differences are established between them with regard to sex and age distribution of patients, growth type and macroscopical appearance, the degree of cell atypy, and invasiveness into the stomach wall, functional activity of tumour cells, correlation between the stroma and parenchyma.
Morphological and mammographic study of small (less than 1 cm) focal mammary gland lesions of 170 women revealed foci of typical epithelium proliferation of the ducts and lobules, fibrosing adenosis, small duct papillomas and fibroadenoma, intraductal and ductal carcinoma in situ, sometimes with small invasion foci, infiltrating carcinoma, infiltrating lobular carcinoma. Peculiarities of small focal lesion morphology determine the mammographic picture. Analysis of nodular shadows on the mammogram gives as a rule a possibility to differentiate between benign conditions (focal proliferation of the epithelium, fibroadenoma), early carcinoma (intraductal and lobular in situ, sometimes with small foci of invasion) and infiltrating carcinoma. Calcareous deposits in both benign lesions and carcinomas do not differ mammographically. Morphogenetic link was revealed between foci of epithelium proliferation (benign displasia), intraductal and lobular carcinoma in situ and infiltrating carcinoma. Among 65 cases of non-palpable carcinoma, 31 (47.7%) were classified as early carcinoma and 34 (52.3%) as infiltrating carcinoma with a relatively low histological degree of malignancy. In both groups a good postoperative survival was observed.
DNA content in the tumour cell nuclei was studied in 16 cases of early stomach carcinoma and in the adjacent areas of the foveolar epithelium dysplasia and metaplastic intestinal epithelium. One wave microspectrophotometry was used; the slides were stained with gallocyanin-chrome alum. The number of DNA synthesizing diploid cells was increasing with the increase of the dysplasia degree. The number of tetraploid cells was higher and the signs of aneuploidy appeared in the areas of noninvasive carcinoma. The stem line in early invasive carcinoma was represented by the diploid cells. The increase of cell atypia in tubular and papillary adenocarcinoma is followed by increase of the tetraploid cell number and by the appearance of polyploidy and aneuploidy. Both undifferentiated and goblet-cell carcinomas have similar parameters of the DNA histogram. DNA content allows an objective judgement on the degree of an early carcinoma cell atypia and differentiation of the advanced dysplasia and noninvasive carcinoma.
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On the basis of literature the markers of organ and tissue tumour specificity are reviewed. Signs of specific cell differentiation, similarity of tumour cells to the homologous cells of normal tissues are found electron-microscopically, histochemically (immunohistochemically and histoenzymochemically) in many organ-nonspecific tumours. Carcinoma cells with the ultrastructural features of organospecificity can be considered to be the cells-markers of the organ appurtenance of the tumor. Biological tumour markers (oncofetal antigens, ectopic hormones and enzymes) revealed until now in the serum and secretes of a tumour-bearing host, are not specific for a tumour of a single type. The search of criteria of tumour organospecificity (so-called biological, ultrastructural and histochemical markers) is necessary for precise tumour verification, determination of its histo- and cytogenesis and its primary location.
Peripheral pulmonary carcinoma was analysed retrospectively histologically, histochemically, and cytologically. The examination material (smears taken at percutaneous thoracic aspirational biopsy, resected lung or lung lobe) had been obtained from 113 patients with PPC among whom 85 patients underwent pulmon- or lobe-ectomy. Cytological examination of specimens from percutaneous thoracic biopsy allowed the diagnosis of PPC to be established in 90.6% of cases and to determine correctly the histological type of cancer in 85.7%. No regular correlation between the levels of tissue and cellular differentiation in squamous cell carcinoma and adenocarcinoma was found. Argyrophilic granules (Grimelius reaction) were detected in cells of combined oat cell carcinoma and small cell carcinoma of transitional type. Because of the existence of combined tumors in the lungs consisting of cells of different types of differentiation it is suggested that complex histological types of pulmonary carcinoma can develop from a common polypotent precursor cell.
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