Prognostic parameters of renal cell carcinoma.
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Carcinoma, Renal Cell↗
Biomedical subjects
W Thoenes
Publications and source records attributed to W Thoenes.
The human chromophobe cell renal carcinoma: its probable relation to intercalated cells of the collecting duct.
In the present study we have examined ten cases of the chromophobe type renal cell carcinoma. This type of tumor is distinguished from the other carcinomas of the kidney with light cytoplasm (formerly called "hypernephroid") by (a) a positive Hale's iron colloid stain of the cytoplasm, (b) the occurrence of numerous invaginated vesicles within the cytoplasm that resemble the invaginated vesicles of intercalated cells of the collecting duct system, and (c) a positive immunoreaction of both the plasma membrane and the cytoplasm with antibodies to the epithelial membrane antigen (EMA) and carbonic anhydrase C (CAC), respectively. Unlike oncocytomas, which also express CAC and EMA, the chromophobe renal cell carcinoma does not express the erythrocyte anion exchanger band 3. These findings strongly indicate that chromophobe renal cell carcinomas as well as oncocytomas of the kidney are histogenetically related to the two populations of intercalated cells of the collecting duct system. Thus, both tumors represent examples of renal tumors which disprove the broadly accepted hypothesis that all epithelial tumors of the kidney are histogenetically related to the proximal tubule.
Anion Exchange Resins↗
HSV hepatitis in the mouse: a light and electron microscopic study with immunohistology and in situ hybridization.
In order to characterize better the morphology and immune response in acute necrotizing HSV infection, murine HSV hepatitis was examined. BALB/c mice were inoculated intraperitoneally with 10(6) plaque-forming units (PFU) of HSV-1 (Lenette) and HSV-2 (D316). In both groups half the animals were pretreated with silica particles to block macrophage function. Up to 6 days after infection four mice from each group were sacrificed at daily intervals and the livers were examined by light and electron microscopy, immunohistology, in situ hybridization, combined immunohistology/in situ hybridization and titration of viral PFU. HSV-2 infected mice developed severe necrotizing hepatitis with persistence of HSV in the liver tissue until the end of the study. HSV-1 infected mice rapidly eliminated the virus and revealed only small necrotic foci. Early phase alterations and necrotic phase lesions were distinguished and characterized and morphologic evidence of a direct cytopathic effect of HSV was detected. A specific immune reaction in late stages appeared to be mediated by T4-positive T-lymphocytes. In situ hybridization and immunohistochemistry showed a close correlation with virus titration and were valuable in characterizing early phases and in the assessment of prognosis and differential diagnosis.
Animals↗
Prognostic parameters in renal cell carcinoma--a new approach.
The prognostic potential of the parameters TNM staging, Robson staging, grading, cell type, growth pattern, and patient age was investigated for 431 patients with operated renal cell carcinoma (RCC). In the individual analyses, staging and grading attained the best results, whereby Robson staging proved to be superior to TNM staging by comparison. Morphological parameters had a more modest effect on the prognosis, but this should not be underestimated. A scale of points based on a comparative biometric evaluation of the various parameters was devised. From this scale, three significantly distinct prognostic groups evolved with a correct prognosis of over 80% on the average for an individual case. In comparison with other proposals for assessing prognosis for RCCs, the suggested scale of points had the greatest prognostic potential.
Adult↗
[President's opening address. Research in Pathology].
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Forecasting↗
[Establishment and characterization of phenotypically distinct cell lines from a single chromophilic renal cell carcinoma].
Two phenotypically different permanent cell lines (A and B) were established from a single human chromophilic renal cell carcinoma. The cells of cell line A were large and spindle-shaped, exhibiting a mean doubling time of 32 hours and a saturation density of 85,000 cells/sqcm. The cells of cell line B were smaller and polygonal, exhibiting a mean doubling time of 19 hours and a saturation density of 370,000 cells/sqcm. Cell line A proved to be non-tumorigenic after heterotransplantation into nude mice, whereas cell line B produced rapidly growing carcinomas. These transplant tumors were non-metastatic after subcutaneous implantation, but highly metastatic after renal implantation indicating that the biological behaviour of malignant tumors may be affected by the host tissue.
Carcinoma, Renal Cell↗
Histologic features in autoimmune hepatitis.
In order to see if the term of "plasma cell hepatitis", dating back to the early sixties, is still valid as a morphological diagnosis for autoimmune chronic hepatitis (AICH), and to find out if the existence of several subgroups is reflected by histopathology, we investigated 26 patients with chronic hepatitis, who met the criteria of autoimmune hepatitis based on tests for antinuclear, anti-smooth muscle antibodies (SMA) and on immunoassays for liver-kidney-microsomal (LKM) antigen, liver membrane antigen (LMA), and soluble liver antigen (SLA). In our material autoimmune hepatitis represent the entire spectrum of chronic hepatitis with variable inflammatory activity ranging from chronic persistent hepatitis to severe inflammatory lesions in chronic active hepatitis with transition to cirrhosis. When compared to viral chronic hepatitis A and non-A, non-B, however, characteristic features can be evaluated consisting in broad hypocellular areas of collapse and microacinar transformation of hepatocytes with hydropic swelling being the predominant type of cell lesion. Eosinophilic clumping and acidophilic necrosis were insignificant. Plasma cells were not a constituent feature of AICH. From this histopathologic pattern it may be concluded that the disease seems to run a sluggish course in most patients, however, in few cases a dramatic development may determine the disease with fatal acute episodes which are terminated by death or fade into slow progression. The different subgroups could not be distinguished by histopathology.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[The pathology of glomerulonephritis].
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Biopsy↗
[Current pathology of the kidney. On the way to the 73d meeting of the German Society of Pathology in Koblenz!].
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Humans↗
Chromophobe cell renal carcinoma and its variants--a report on 32 cases.
This paper reports on 32 chromophobe cell renal carcinomas observed in 697 renal cell cancers (RCC) of adults (peak in the sixth decade of life). The chromophobe cell-type differs from other types of RCC macroscopically, the cut-surface being predominantly of grey-beige colour. Histologically, there are two variants: one is the typical (light) variant (n = 22) and the other is eosinophilic (n = 10). Both variants have in common (a) reaction of the cytoplasm with Hale's acid iron colloid; (b) electron microscopic detection of cytoplasmic microvesicles (150-300 nm), frequently with 'inner vesicles', and (c) low glycogen content in comparison with the clear cell carcinoma. Immunocytochemical investigations on the intermediate filaments show a positive reaction for cytokeratins No. 18 (uniformly) and Nos. 7 and 19 (to varying extents) for both variants, whereas vimentin was not found in any of these carcinomas, in contrast to the clear-cell type. The cytomorphological grading revealed predominantly G II tumours. A lymph node metastasis was found in one patient. On the basis of the mortality curves determined, the prognosis for patients with chromophobe cell carcinomas is more favourable than that of the clear-cell type. In terms of differential diagnosis, on the one hand, the typical (light) variant of the chromophobe cell RCC must be delimited from the clear-cell RCC, and on the other hand, the eosinophilic variant must be distinguished from the chromophilic or 'granular' RCC. Microscopic, histological, histochemical, electron microscopic, and intermediate filament analysis results document that the chromophobe cell type of RCC is a distinct entity. The implications for the nomenclature of RCC, especially with regard to the 'granular' type, are discussed.
Adult↗
Acute human pyelonephritis: leukocytic infiltration of tubules and localization of bacteria.
The fine structural details of how leukocytes appear in the lumen of tubules and the localization of bacteria in the tubulo-interstitial space were studied by light and electronmicroscopy in renal cortical biopsy specimens from three patients with acute pyelonephritis. The cells of interstitial infiltrates infiltrated and sometimes disrupted the cortical collecting tubules preferentially, while inflammatory infiltration of the proximal and distal convoluted tubules occurred more rarely. Since the emigration of tubular wall-localized individual leukocytes into the lumen was not observed even in long series of thin sections, focal inflammatory disruption of the uriniferous ducts was considered to be the morphological basis of the intratubular accumulation of leukocytes. The structural simplicity of the collecting tubular cells is suggested to be the reason for their preferential involvement in the drainage of the interstitial suppuration, although a role for specific carbohydrate receptors cannot be excluded. The bacteria were usually found within the neutrophilic granulocytes and macrophages of the interstitial infiltrates, and within and among the cells of leukocyte casts. Additionally, pure bacterial colonies were noticed in the lumen of a few collecting tubules. The problem of the adherence of the bacteria to the surface of the tubular cells is discussed.
Acute Disease↗
Intercalated cells as a probable source for the development of renal oncocytoma.
Renal oncocytoma is a distinct type of epithelial tumor said to arise from the collecting duct system. Here we show that in nine of ten oncocytomas the tumor cells expressed an analog of the erythrocyte anion exchanger band 3. In the normal kidney band 3 is confined to the basolateral surface of the majority of intercalated cells which comprise up to 50% of the cortical collecting duct epithelium. Carbonic anhydrase c is another protein abundant in intercalated cells, and this was also expressed in six of the ten oncocytomas investigated. Immunoreactivity specific for band 3 and carbonic anhydrase c was not detected in any of the 20 renal cell carcinomas examined. At favourable section planes direct transitions between normal collecting ducts and oncocytic tubules were observed. These findings suggest that oncocytomas may develop from intercalated cells of the collecting duct epithelium.
Adenoma↗
Microvascular injury and repair in acute human bacterial pyelonephritis.
Acute inflammatory cell-capillary endothelial cell interactions, related to injury and repair, were investigated light and electron microscopically in acute human bacterial pyelonephritis. In inflammatory infiltrate-adjacent microvessels, the small capillaries were completely occluded by leukocyte plugs and the large capillaries were densely filled with acute inflammatory cells adhering to the endothelium. Severe damage to small and large capillaries was observed around endothelium adherent, degranulated neutrophil granulocytes containing phagocytosed bacteria. There were spaces in the endothelium, degradation of the vascular basement membrane, of the perivascular interstitial matrix and of collagen fibrils, with fibrin deposition and vessel wall fragmentation. In the small capillaries relatively distant from the interstitial infiltrates, emigration of leukocytes was frequently seen. Around the escaping cells the endothelial lining displayed occasional discontinuities, allowing leakage of vascular fluid into the interstitial space. Some small capillaries not related to the infiltrate were occluded by fibrin thrombi with apparent damage to the endothelial cells and disruption of the capillary wall. Various reparative changes were noticed in association with this change including capillary neovascularization. The findings confirm the existence of polymorphonuclear leukocyte-mediated injury of capillaries during the development of inflammatory responses in acute pyelonephritis.
Acute Disease↗
Freeze-fracture features of epithelioid cells, multinucleated giant cells, and phagocytic macrophages. Investigations using the model of experimental autoimmune (anti-TBM) tubulo-interstitial nephritis.
The freeze-fracture morphology of epithelioid cells, multinucleated giant cells (Langhans' type), and phagocytic macrophages was investigated. The intensely folded and interdigitating surface membranes of epithelioid cells and multinucleated giant cells displayed no specialized areas of cell contact. The size of the intramembranous particles (IMP) and the fact that the area density of IMPs was higher in the cytoplasmic (P) faces than in the external (E) faces of the cell membranes agreed with observations in other eukaryotic cells. The area densities of the IMPs suggest lower transport rates of molecules across the cell membranes of granuloma cells than of certain epithelial cells. Small pits were detected in the surface membranes of the granuloma cells but an extrusion of granules was not observed. The cytoplasmic granules displayed very different sizes and shapes ranging from spherical to rod-shaped. The latter type of granules (probably primary lysosomes) dominated in multinucleated giant cells. The granule membranes were studded with IMPs whose area densities increased with the granule size. Multilamellar bodies with smooth (lipid) fracture faces were found only in phagocytic macrophages. The nuclear pores of the granuloma cells were distributed over the entire surfaces of the nuclei and displayed moderate clustering. The values of the area densities of the nuclear pores were in keeping with the values observed in mammalian and human epithelial or mesenchymal cells, indicating similar exchange rates of molecules between the nucleoplasm and the cytoplasm in these different cell types. In a single phagocytic macrophage the E-face of the inner membrane of the nuclear envelope displayed a network of fine filaments whose nature is at present unknown.
Animals↗
Cytoplasmic microvesicles in chromophobe cell renal carcinoma demonstrated by freeze fracture.
In the chromophobe cell type of renal carcinoma, cytoplasmic microvesicles (frequently with "inner vesicles") demonstrable by transmission electron microscopy are one of the most important diagnostic features. The present paper reports on these microvesicles in freeze fracture replicas. Their diameter is mainly between 140 and 300 micron, but smaller and very much larger vesicles may also occur. The vesicle membrane is devoid of, or contains only scanty intramembranous particles. Cytoplasmic invaginations, probably the precursors of "inner vesicles" can also be detected. Connections with the agranular endoplasmic reticulum, mitochondria or other cell components could not be documented. Larger vacuoles limited by a membrane and containing large numbers of microvesicles have been interpreted as autophagic vacuoles. In freeze fracture replicas, there are marked differences between the chromophobe cell and the clear cell type of renal carcinoma, providing further evidence that the chromophobe cell type is a distinct entity.
Carcinoma, Renal Cell↗
Alterations of glomerular podocytic processes in immunologically mediated glomerular disorders.
The importance of the relationship between the alteration of podocytic processes (PP) and proteinuria has been controversial for almost 30 years. In spite of several morphometric studies the range of PP alterations in different proteinuric conditions has gone unnoticed. Thus, we studied the distribution of abnormally broadened PP in different glomerulopathies and in normal controls (children and adults). We found a highly variable mean PP-width in all proteinuric patients, values that were, however, always clearly distinct from normal controls in children and adults. A correlation between the extent of PP alteration and the amount of proteinuria was not found (r = 0.09) for the group as a whole or for the different clinico-pathological entities. In proteinuric patients 15 to 50% of all PP were broadened and covered 40 to 60% of the total length of the peripheral capillary loop. We conclude that the alteration of PP in various proteinuric conditions is variable and does not correlate with the level of proteinuria. These studies further suggest that other mechanisms, possible hemodynamic adaptation in response to the capillary wall injury, might play a role in the permeability changes observed in these patients.
Adult↗
Expression of intermediate filament proteins in subtypes of renal cell carcinomas and in renal oncocytomas. Distinction of two classes of renal cell tumors.
We examined the expression of the diverse cytokeratin (CK) polypeptides as well as vimentin in human renal cell carcinomas of various subtypes and in renal oncocytomas by applying both two-dimensional gel electrophoresis and immunocytochemistry by using polypeptide-specific monoclonal antibodies. The tumors were classified according to the guidelines of the World Health Organization, with some modifications based primarily on recently proposed cytomorphological criteria. All clear cell carcinomas (G I, G II; N = 20) co-expressed CKs nos. 8 and 18, and vimentin, with CK no. 19 being present in 13 of the 20 cases and exhibiting a heterogeneous distribution. Dedifferentiated carcinomas (G III; N = 8) also co-expressed CKs nos. 8 and 18 as well as vimentin, but in addition, exhibited CK no. 19 and, in many cases, CK no. 7; in 1 case, only vimentin was expressed. Both eosinophilic-granular (N = 3) and basophilic (small cell cuboidal; N = 6) carcinomas contained CKs nos. 8 and 18, and the co-expression of vimentin was a consistent feature of these tumors; CK no. 19 was found in all of these cases, while CK no. 7 was present in the majority. In chromophobe cell carcinomas (N = 8), in contrast to all of the other carcinoma types, no vimentin was detected in the tumor cells, with only CKs nos. 8, 18, and to a variable extent 7, being present. Similarly, oncocytomas (N = 8) lacked vimentin and exhibited only CKs nos. 8 and 18. Conspicuous scattered CK no. 19-positive cells were found in these two last tumor types. No CK polypeptides other than simple-epithelium-type CKs (nos. 7, 8, 18, and 19) were detected in any of the tumors studied. These results indicate that, in renal cell tumors, the expression of intermediate-filament proteins is strikingly correlated with the specific morphologic appearance. While the co-expression of CKs nos. 8 and 18 and vimentin was a surprisingly consistent feature of the most common subtypes of renal cell carcinomas, CK no. 19 exhibited remarkable heterogeneity of expression both within individual tumors and between different tumors, the expression patterns of this CK being correlated to the tumor subtypes. The consistent absence of vimentin in chromophobe cell carcinomas and oncocytomas makes it possible to define these as a separate class of renal cell tumors. This finding supports the view that chromophobe cell carcinomas represent a distinct tumor entity and points to their close phenotypic relationship to benign oncocytomas as well as to normal renal tubules.
Adenoma↗
Follow-up studies of three subtypes of acute postinfectious glomerulonephritis ascertained by renal biopsy.
Quantitative correlative investigations by means of light, immunofluorescence and electron microscopy carried out in the early phase of the disease on 58 patients (children and adults) with acute postinfectious glomerulonephritis (APGN) formed the basis of subtyping APGN into a starry sky type, a mesangial type and a garland type [Sorger et al. 1982 and 1983]. The subtypes also showed differences in the clinical picture. The garland type was of special interest since most patients had severe proteinuria. This caused us to follow-up the patients with these three subtypes (up to 10 years and 7 months). Proteinuria proved to be the most reliable follow-up parameter. A comparison of the three groups showed that proteinuria rapidly declined as a rule in the patients with the starry sky and the mesangial patterns. In the garland pattern there were also cases with a complete disappearance of proteinuria, especially in younger patients, but other patients still had a distinct proteinuria after months to years indicating a protracted or chronic course. The morphological findings of the rebiopsies correlated with the clinical courses, especially with the course of proteinuria. The three morphological subtypes are thus significant for estimating the prognosis of APGN, which is favorable as a rule in patients with the starry sky and mesangial types, but much more unfavorable in patients with the garland type. Even if fewer cases with demonstrated streptococcal etiology were found in the garland pattern group, i.e., among patients with the most uncertain prognosis, than in the remaining groups, these differences were not statistically significant. Therefore, our investigations do not provide any indications that different etiological factors are responsible for the three subtypes. The individual immune response of the host body is likely to be very much more decisive.
Acute Disease↗