Showing papers in "Virchows Archiv in 1985"

Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus.

Abstract: Based on the light microscopical features of normal thymic epithelial cells, human thymoma was divided in different types, namely cortical, medullary, and mixed ones, according to the epithelial cell (EC) type. Lymphoid cell populations with morphological features of either cortical or medullary thymocytes were found according to different types of EC in thymoma. The histological variation of the different types of thymoma are demonstrated. In a retrospective study of 58 thymomas and 13 thymic carcinomas, malignant invasive character as well as the occurrence of myasthenia gravis were both found to be related to the neoplastic proliferation of the cortical epithelial cells, whereas in the usual mixed type of thymoma and the medullary type no gross invasion or metastases were noticed. These results are discussed in view of recent concepts and immunological findings of thymus microarchitecture.

Are hepatolithiasis and cholangiocarcinoma aetiologically related? A morphological study of 12 cases of hepatolithiasis associated with cholangiocarcinoma.

Abstract: A few cases of cholangiocarcinoma (CC) related to hepatolithiasis have been reported to date, but the aetiological relationship remains unclear. In an attempt to clarify the relationship between two phenomena, we examined morphologically 12 cases of hepatolithiasis associated with CC and 26 cases of hepatolithiasis without CC, with the aid of immunohistochemical staining for carcinoembryonic antigen (CEA). In the livers where both hepatolithiasis and CC were found, the carcinoma spread along the lumenal surface of the stone-containing bile ducts and invaded the ductal walls. Features of “chronic proliferative cholangitis” which was a basic feature of hepatolithiasis, were found within the bile duct walls where carcinoma was invading. In some cases of chronic proliferative cholangitis with hepatolithiasis in the absence of CC, atypical epithelial hyperplasia was noted. Atypical epithelial hyperplasia was also found in bile ducts adjacent to and remote from CC. Atypical epithelial hyperplasia was positive for CEA. The data lead us to speculate that chronic proliferative cholangitis in the presence of hepatolithiasis can undergo progressive changes to atypical epithelial hyperplasia which may in turn progress to CC.

Malignant peripheral neuroectodermal tumours of childhood and adolescence.

Abstract: Seventeen cases of malignant peripheral neuroectodermal tumour (MPNT) were studied by means of light microscopy, immunohistochemistry and electron microscopy There were nine males and eight females The mean age of the 17 patients was 10 years with a range of seven months to 20 years The vast majority of tumours was located in the trunk Histologically, they closely resembled Ewing's sarcoma, although minor differences were obvious Special findings included ganglion cells and Flexner rosettes In 10/11 cases positive staining for neuron-specific enolase (NSE) was obtained Five of 10 tumours were positive for protein S-100 Three contained vimentin, two neurofilaments and one vimentin, neurofilaments and GFAP Neurosecretory granules were noted in the three cases studied Five patients died, three are alive with disease and five patients are alive without evidence of disease It is concluded that these tumours form a homogeneous group, although the grade of differentiation varies The prognosis in most cases is poor Distinction from Ewing's sarcoma is possible by staining for NSE and by electron microscopy

Immunohistochemical distribution of S-100 protein and glial fibrillary acidic protein in normal and neoplastic salivary glands.

Abstract: Immunohistochemical localization of S-100 protein, its α andβ subunits, and glial fibrillary acidic protein (GFAP) in normal and neoplastic salivary glands was studied by the peroxidase-antiperoxidase method and immunoblot analysis. Positive immunostaining for S-100 protein was observed in pleomorphic adenoma, adenolymphoma, tubular adenoma, adenoid cystic carcinoma, acinic cell tumour, adenocarcinoma and carcinoma in pleomorphic adenoma. S-100 protein was localized in myoepithelial cells, epithelial cells of intercalated ducts and serous acinar cells of normal salivary gland. Both α andβ subunits of S-100 protein showed almost identical distribution in normal and neoplastic salivary glands, but skeletal muscle cells were α-positive/β-negative whereas Schwann cells and fat cells were α-negative/β-positive in the stroma and neighbouring tissue. GFAP was only found in pleomorphic adenoma and its malignant counterpart. Immunoblot analysis showed that the GFAP-related antigen consisted of several polypeptide bands with a molecular weight ranging between 35,000 to 50,000 daltons.

Immunohistochemical characterization of an anti-epithelial monoclonal antibody (mAB lu-5)

Abstract: A mouse monoclonal antibody (mAB lu-5) was prepared using a lung cancer cell line as an antigen. The selected clone produces an IgG with a gamma-1 heavy chain and a kappa-light-chain. Immunohistochemical testing of mAB lu-5 on 117 normal tissue biopsies and 474 tumours revealed reactivity with an intracytoplasmic, formaldehyderesistant antigen present in most epithelial and mesothelial cells, but absent in mesenchymal cells. The antibody can therefore be used as a first order, pan-epithelial marker. It proved also useful for fast tumour diagnosis on frozen sections.

Co-expression of cytokeratin and vimentin intermediate-sized filaments in renal cell carcinomas. Comparative study of the intermediate-sized filament distribution in renal cell carcinomas and normal human kidney.

Abstract: The expression of intermediate-sized filaments (IF) was examined by immunocytochemical methods in 40 primary renal cell carcinomas and compared with the IF distribution in the normal adult human kidney. All tumours stained positively with cytokeratin IF antibodies. Co-expression of cytokeratins and vimentin was observed in 21/40 (52,5%) renal carcinomas. Double immunofluorescence labelling demonstrated that in most of these cases tumour cells contained both cytokeratin and vimentin type IF. In normal human kidneys, cells of the various tubular segments disclosed a positive reaction with cytokeratin antibodies in a different intensity and intracellular localization. Co-expression of cytokeratin and vimentin IF in normal adult human kidneys has never been observed. From a histogenetic point of view, co-expression of cytokeratins and vimentin in renal cell carcinoma obviously represents an atavistic phenomenon since vimentin is re-expressed by these tumour cells during neoplastic transformation. This finding indicates the metanephric origin of the renal parenchyma. In surgical pathology the possibility of very rare co-expression of cytokeratin and vimentin IF within tumour cells should be considered, particularly in the differential diagnosis of clear cell carcinomas.

Myofibroblastic stromal reaction in carcinoma of the breast: variations of collagenous matrix and structural glycoproteins.

Abstract: The matrix of mammary dysplasia, noninvasive ductal carcinoma, and invasive lobular and ductal carcinoma was analyzed by indirect immunofluorescence using antibodies to types I, proIII, III, and IV collagens, and laminin and fibronectin. Types proIII and III collagens were present in increased amounts in invasive carcinomas and were most abundant in the "young" edematous mesenchyme, areas corresponding to the peripheral invasive cellular front. Type I collagen was distributed throughout the matrix of invasive carcinomas but was most prominent within the central sclerotic zone of the neoplasms. Mammary dysplasia and noninvasive ductal carcinomas showed a uniform fibrillar and granular distribution of all types of collagen. In all but two cases of invasive carcinoma, staining with anti-laminin and anti-type IV collagen demonstrated the loss of basement membranes around tumor cells. In contrast, fluorescence pattern in noninvasive ductal carcinoma and dysplasia revealed an intact basement membrane. The distribution of fibronectin was similar to types proIII and III collagen. These findings support and extend our previous studies which suggested an analogy between the dynamics of matrix changes in granulation tissue and invasive carcinomas. These data also strengthen the concept that the myofibroblast could be a pivotal cell involved in the synthesis and redistribution of matricial proteins. The loss of basement membrane in invasive carcinomas appears to be an initial step for inducing the matricial alterations.

Bronchogenic cyst in the abdomen

Abstract: A bronchogenic cyst was found in the abdomen, in the retroperitoneum adjacent to the superior pancreatic body. The cyst was unilocular and contained about 100 ml pale yellow mucinous fluid. Microscopic examination revealed a pseudostratified columnar ciliated or cuboidal epithelium, seromucous glands, smooth muscle and cartilage, the distinctive features of bronchogenic cysts. This aberrant location of the cyst is explicable if abnormal buds of the tracheobronchial tree are pinched off and migrate into the abdomen in an early embryonic stage before the canal linking the abdominal with the thoracic cavity is closed by fusion of the future components of the diaphragm.

Cellular characteristics of neoplastic angioendotheliosis. An immunohistological marker study of 6 cases.

Abstract: Neoplastic angioendotheliosis (NAE) is a rare, mostly fatal disease characterized by proliferation of large blastoid cells in small vessels of various organs. The origin of neoplastic cells remain undetermined. In this study, cell markers were studied immunohistologically on paraffin sections of six cases of NAE, by applying avidin-biotin-peroxidase (ABC) method and five antibodies which can demonstrate marker antigens on formalin fixed and paraffin embedded specimens. It was shown that the neoplastic cells were heavily stained with an anti-B lymphocyte monoclonal antibody LN-1 (6/6), moderately stained with another anti-B lymphocyte antibody LN-2 (5/6) and heavily stained with a monoclonal antibody which reacts with all levels of leukocytes (Dako-LC) (6/6). The cells did not show positive reaction with an anti-myelomonocytic antibody anti-Leu M1. The reaction against anti-Factor VIII, which can depict endothelial cells, was mostly negative, and if positive, was faint and undefinite, leading to an assumption that the reaction was against antigens in serum and not against neoplastic cells. These results suggest that the neoplastic cells of NAE are in the B lymphocyte lineage.

Immunohistological evidences of cortical and medullary differentiation in thymoma

Abstract: The phenotypical characteristics of human epithelial and lymphoid cells have been studied with immunohistochemical methods on frozen sections of 12 thymomas. On the basis of the cytohistological characteristics of thymoma epithelial cells (EC) the thymomas were divided in cortical, medullary and mixed types, according to recently developed light microscopical criteria. When tested with a series of monoclonal antibodies, thymoma EC were all stained by the antibody Ki-M3 (as in the thymus), but reacted with anti-HLA-DR, anti-HLA-A,B,C and with a new monoclonal antibody to cortical EC, 21A6, to a lesser extent and with weaker, variable intensity in comparison with the normal thymus. Cortical type thymomas were most reactive and the medullary type almost negative. Thymomas, like normal thymus showed different immunoreactivity patterns with antibodies to prekeratins of different specificities. Cortical type thymomas and areas in mixed thymoma showed an EC staining with the antibody to non-squamous type keratin (35 beta H11) whereas medullary type thymomas and areas showed staining with antibodies to squamous-type keratin (34 beta E12-IV/82) in addition. Lymphoid cells with cortical (OKT6+, Leu 1 weakly+, Leu 2a+, Leu 3a+) or mature medullary (OKT6-, Leu 1 strongly+, Leu 2a or Leu 3a+) phenotype were found to colonize tumours with different EC types. These immunohistochemical findings largely confirm our earlier cytological distinction of thymoma EC. In addition important differences have been observed in neoplastic cortical EC concerning the HLA-DR and 21A6 immunoreactivity that may be intimately related to the neoplastic process and paraneoplastic immune phenomena.

Partial regression in thin primary cutaneous malignant melanomas clinical stage I. A study of 486 cases.

Abstract: 486 patients with primary cutaneous malignant melanoma clinical stage I were examined in order to evaluate the prognostic importance of partial regression in thin lesions. All the melanomas measured 1 mm or less in maximal thickness. The study showed that past regression with fibrotic scar tissue adversely affected survival in patients with thin melanomas. The 10 year survival was 95% for patients without regression in contrast to 79% for patients with past regression. It was, furthermore, demonstrated that active regression without fibrotic scar tissue did not influence survival significantly.

Survival with primary cutaneous malignant melanoma, evaluated from 2012 cases. A multivariate regression analysis.

Abstract: Cox's multivariate regression model for survival data was applied to 2,012 patients with primary cutaneous melanoma in order to evaluate the relative prognostic value of numerous clinical and histological variables and to establish their prognostically most efficient combination. The material was divided into 4 groups according to the size of resection margin of the primary lesion (<2.0 cm, 2.0 cm, 2.1–4.9 cm, and ≧ 5.0 cm). Data were analysed separately in these 4 groups and equivalent results were obtained. The risk factors were clinical stage, site of tumour, tumour thickness, level of invasion, mitotic activity, ulceration, lymphocytic reaction, predominant type of invasive tumour cell and partial regression. When accounting for these factors, histological type, nuclear pleomorphism, nucleolar size, vascular invasion, pigmentation, verrucous growth pattern, and dermal elastosis were without prognostic influence. The effect of sex and age of patient was uncertain and both variables, therefore, were retained in the model. By using Cox's method it is possible to make a qualified estimate of the survival for the individual patient.

The immunogold-silver staining method. A powerful tool in histopathology.

Abstract: Immunostaining of routinely fixed, wax embedded tissues may present problems to the pathologist since destruction of antigens can lead to false negative results. In an attempt to overcome this problem, we have compared the results of the standard peroxidase anti-peroxidase (PAP) method with those obtained using the newly developed and very sensitive immunogold-silver staining (IGSS) method. Sections from routine histopathological material as well as from normal tissue specimens were used in the comparison. Antisera to a variety of antigens commonly employed in pathology were used, including regulatory peptides and a range of other markers. In all cases the IGSS method was found to give superior or at least equal results to those obtained with the PAP technique. In some cases staining was obtained with IGSS method when the PAP technique gave no result. The intense black reaction product allowed much easier and more rapid screening of immunostained preparations as well as permitting sections to be counterstained with routine histological stains such as haematoxylin and eosin. It is therefore suggested that immunogold-silver staining is a valuable technique for the pathologist, particularly when examining overfixed or badly processed tissues.

Malignant rhabdoid tumor of the prostatic region. Immunohistological and ultrastructural evidence for epithelial origin.

Abstract: We describe a malignant rhabdoid tumour of the prostatic region in a 14-year old boy. The tumour showed positive immunoreactivity for epidermal prekeratin, monoclonal cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and monoclonal vimentin but was negative for myoglobin, alfa-fetoprotein and lysozyme. Electron microscopy revealed pleomorphic cells with collections of paranuclear intermediate filaments, sheaves of tonofilaments and abundant microvilli in some tumour cells. Epithelial derivation was also suggested by occasional intracytoplasmic lumina and rare cell junctions.

Characteristics of the plaque under a coronary thrombus

Abstract: Young men dying suddenly and autopsied by the coroner sometimes have coronary thrombosis at a relatively early stage of arteriosclerosis. The plaques under such thrombi often have a complex of features, a) rupture, b) hemorrhage, c) medial destruction, d) nodular collections of foam cells, e) calcification, f) cellular infiltrates of the fibrous cap, fibrous base and adventitia, and g) a newly described kind of phagocytic activity at the boundary between the necrotic core and the fibrous base of the plaque. Commonplace innocuous plaques in most middle and old aged subjects without heart disease also often have some of these features. What structural characteristics might distinguish rare thrombogenic from commonplace innocuous plaques? Twenty-one thrombotic plaques from 18 cases of sudden coronary heart disease (CHD) death were histologically compared with 129 nonthrombotic plaques from these same 18 cases, 85 plaques from 23 cases of CHD death due to arteriosclerotic occlusion, and 94 plaques from 22 cases having no CHD. Plaques with thrombosis all had necrotic cores; plaques for comparison with these were therefore chosen all to have necrotic cores. Rupture and hemorrhage were found in 90% of thrombotic plaques, with mixing of plaque gruel and blood in the thrombus. Medial destruction, foam cells and calcification (features c, d, and e) were commonplace in all types of plaques. Small-cell infiltrates and atherophagocytosis (features f or g) were found in 72–94% of the 21 thrombotic plaques, but only in 18–24% of the 94 not CHD plaques. The necrotic core, characterized by crystalline cholesterol, appears to incite cellular responses in some plaques but not others; those responses distinguish thrombogenesis. The findings imply that thrombogenicity and its accompanying plaque cellularity are incited not by cholesterol, but by some trace or minor component of the plaque gruel of the necrotic core. The possibility of testing these hypotheses by practical methods has been shown to be feasible.

The use of vimentin antibodies in the diagnosis of malignant mesothelioma

Abstract: An immunohistochemical investigation of vimentin, an intermediate filament, was carried out on formalin fixed paraffin embedded sections of 44 malignant mesotheliomas of the pleura and 24 pulmonary adenocarcinomas, in order to assess its value in differential diagnosis. Seventy-five percent of the malignant mesotheliomas showed positive staining for vimentin. An unexpected finding was the presence of vimentin in 46% of the pulmonary adenocarcinomas. In either case there was no correlation between the presence of vimentin and the histological types or grades of differentiation. The overall level of vimentin staining was significantly greater in the malignant mesotheliomas than in the pulmonary adenocarcinomas but no single antibody dilution was found to provide clear cut separation of the two groups. Vimentin does not appear to be a simple discriminatory marker of malignant mesothelioma.

Angiomatoid malignant fibrous histiocytoma : Evidence for the histiocytic origin of tumor cells

Abstract: The results of an histological, immunocytochemical and electron microscopic study of an angiomatoid malignant fibrous histiocytoma are reported. Our results support an histiocytic, rather than an endothelial origin for the tumor cells.

Anti-GBM nephritis in the mouse: severe proteinuria in the heterologous phase

Abstract: Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected anti-bodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.

Aortic intimal monocyte recruitment in the normo and hypercholesterolemic baboon (Papio cynocephalus) - An ultrastructural study: Implications in atherogenesis

Abstract: The ultrastructural features of peripheral blood monocyte margination, migration, and aortic intimal accumulation have been described in the normo- and mildly hypercholesterolemic baboon. Intimal monocyte-macrophage recruitment over fatty streaks and fibro-fatty plaques was enhanced by dietary cholesterol-fat supplementation, resulting in an 8-fold increase in monocyte-macrophages and macrophage-derived foam cells in the subendothelial space. Margination or attachment observed over both plaques and normal areas was not associated with morphologic evidence of endothelial injury. Migration through continuous aortic endothelium was principally between endothelial cells via junctions. Transitional sequences from the typical morphology of the blood monocyte to the lipid-containing macrophage or foam cell were discerned. The intimal accumulation of monocytes and macrophages reinforces our view of atherosclerosis as an inflammatory process, in which monocyte attachment is likely to reflect changes in the endothelial surface-membrane complex and surface charge, while migration to and accumulation in the SES may result from one or more chemoattractants originating in the intima or media.

Organisation of experimental thrombosis by blood cells. Evidence of the transformation of mononuclear cells into myofibroblasts and endothelial cells.

Abstract: To clarify whether thrombus organisation was carried out by local cell activity or by elements of the circulating blood we developed an artifical prosthesis, made of an impermeable polyurethane material with an athrombogenic surface but with a central part consisting of a DACRON velour ring which was thrombogenic. We implanted these devices into the aorta of 10 sheep. In these animals, organisation of the central thrombus by local aortic cells could be excluded. After varying periods of time (2–84 days), the device was removed and the organized thrombus investigated by light and electron microscopy. From our investigations the organisation process with the development of mesenchymal cellular elements proceeded in 3 steps: (1) The activation of the mononuclear macrophage system (2), the appearance of myofibroblastic cells and (3) endothelial formation. The activation of the mononuclear macrophage system is probably induced by chemospecific products of metabolism arising from aging thrombotic material. Apart from mononuclear elements such as monocytes, macrophages, and giant cells we observed fibroblast-like and myofibroblast-like cells. The matrix contained collagen. Endothelium developed on the surface of the organizing thrombus. The final stage was characterized by the formation of a pseudovessel wall, which followed the pattern of the vascular model. Our findings support the hypothesis that a thrombus may be organized by cells derived from the circulating blood.

Tubular ultrastructure in acute renal failure in man: epithelial necrosis and regeneration.

Abstract: It is not clear whether tubular cell necrosis is present or not in acute renal failure (ARF) of ischaemic type ("acute tubular necrosis"). In order to get quantitative data, using precisely defined criteria for tubular cell necrosis, 25 renal biopsies from 24 patients with ARF (11 obtained in the active phase, 14 in the early recovery period) were compared with 12 control biopsies. In all 1959 proximal cells and 1603 distal cells were analysed by electron microscopy. Cellular disintegration was very rare in all groups. Shrinkage necrosis (apoptosis) was not present in the proximal tubules of the controls and was rare in ARF (1.6-2.1%). In the distal tubules of controls 2.7% of all cells showed shrinkage necrosis. The incidence in ARF was not significantly increased. "Non-replacement sites" in distal tubules (probably loci where cells have recently been desquamated) were significantly increased in number (5.2%) in the active phase in ARF compared to controls and recovery. The relative number of regenerating cells was not increased. These data show that there is no widespread necrosis of tubular cells in ARF. The increased incidence in distal tubules of focal, denuded areas of the basement membrane in the active phase of ARF indicates a slightly increased desquamation of cells and/or a failure to cover such sites by adjacent cells. This process is not restricted to the brief induction phase of ARF but continues during the whole active phase.

Primary malignant hepatic tumours in childhood.

Abstract: Twenty-four cases of hepatoblastoma, 14 cases of hepatocellular carcinoma and three cases of malignant mesenchymoma out of a total of 54 primary liver tumours were studied by light microscopy and immunohistochemistry. A remarkable finding in one case of hepatoblastoma and one case of hepatocellular carcinoma was a sarcoid-like reaction in the tumour tissue. Three cases of hepatoblastoma presented a macrotrabecular pattern. Among hepatocellular carcinomas, three cases corresponded to the fibrolamellar variant. By immunohistochemistry, the proportion of cases with positive staining for alpha1-fetoprotein was higher in hepatoblastoma than in hepatocellular carcinoma. HBs-antigen could be demonstrated in non-neoplastic liver cells in two cases of hepatocellular carcinoma, but not in the tumour cells. No strong correlation between histological pattern and prognosis could be established in hepatoblastoma. However, there was a tendency to more aggressive biological behavior in cases with pronounced mitotic activity. The number of mitoses in hepatoblastoma varied widely. As in previous studies, patients with the fibrolamellar variant of hepatocellular carcinoma fared better than those with the classical type of this tumour. Prognosis in malignant mesenchymoma was not as poor as suggested from previous studies.

Histological and cytogenetic findings in a malignant tumor of the chest wall and lung (Askin tumor).

Abstract: This report describes a histological and cytogenetic study of a malignant tumor involving the chest wall and lung (Askin tumor) of a young girl. Although initially considered to represent a variant of Ewing's sarcoma, immunocytochemical studies disclosed neuron-specific enolase in neoplastic cells. Ultrastructural study revealed rare cells which contained microtubules and/or dense core neurosecretory type granules. Cytogenetic analysis of neoplastic cells disclosed a reciprocal translocation (11;22) (q24;q12) and occasional extrachromosomal structures interpreted as double minute chromosomes. The latter finding, an indication of gene amplification, is commonly identified in neural crest-derived neoplasms. These ultrastructural, immunocytochemical, and karyotypic data provide evidence in support of a neuroepithelial histogenesis for the Askin tumor.

Quantitative ultrastructure of human proximal tubules and cortical interstitium in chronic renal disease (hydronephrosis)

Abstract: Surgically removed perfusion-fixed human kidneys with chronic renal disease (hydronephrosis) were studied by electron microscopy in order to determine whether there is a quantitative relationship between ultrastructural changes in proximal tubules in atrophy and changes in the surrounding cortical interstitium. Morphometric techniques were applied to montages of electron micrographs each covering several tubular profiles in the cortical labyrinth and to montages representing cross-sections of individual proximal convoluted tubules at a higher magnification. In order to enable a quantification of the spatial relations between individual tubular cross-sections and adjacent peritubular capillaries a tubulo-capillary index (TCI) was defined. This index was based on the mean distances between individual tubular cross-sections and adjacent peritubular capillaries and on the fraction of tubular circumference facing capillaries. Normal tissue from similarly fixed human nephrectomy specimens, which had been removed mainly because of neoplastic disorders, served as control material. In the hydronephrotic kidneys the relative volume of cortical interstitium (excluding capillaries) covered a range from 19.2–70.3%. Inverse correlations were demonstrated between the relative volume of cortical interstitium and various structural variables of proximal convoluted tubules, including tubular wall volume, the volume of mitochondria and the surface area of basolateral membranes. The TCI showed positive correlations with these tubular variables. No significant correlation was found between the volume fractions of cortical interstitium and capillaries. Finally, it was found that an increase in the volume fraction of the cortical interstitium from 16.2% in controls to 24.7% in cortical areas of hydronephrotic kidneys was associated with a 40–50% reduction in the volume of mitochondria and in the surface area of basolateral membranes in proximal tubules. The results are consistent with a pathogenic interrelationship between tubular and interstitial changes. An important factor in this relationship might be disturbed topographic associations between tubules and blood capillaries caused by the increase in cortical interstitium. The results further show that even slight increases in the cortical interstitial volume are associated with significant quantitative changes in tubular fine structure suggesting impaired tubular functions.

Intraepithelial lymphocytes and macrophages in the normal breast.

Abstract: In this study the presence of intraepithelial cells within the normal breast parenchyma was investigated by electron microscopy and immunocytochemistry. Cells were observed which could be differentiated from the epithelial and myoepithelial cells by their cytoplasmic and nuclear morphology and the absence of cell junctions. Two cell types (lymphocytes and macrophages) were identified ultrastructurally and the bone marrow origin of the cells was confirmed by immunocytochemistry. The intraepithelial lymphocytes and macrophages were present in all samples irrespective of the physiological state. In the “resting”, pregnant, and lactating breast the majority of cells were lymphocytes while in the involuting breast there was a marked increase in the proportion of macrophages. The rarity of lymphoma of the breast may be related to the relatively small amount of lymphoid tissue present and the passive nature of the environment.

Immunohistochemical study of neuron specific enolase and S-100 protein in Hirschsprung's disease.

Abstract: The distribution of whole differentiated neurons in the intestines from 15 children with Hirschsprung's disease was investigated using neuron specific enolase (NSE) and the perineuronal elements were studied using S-100 protein immunostaining. In aganglionic segments, NSE immunoreactive ganglion cells and S-100 positive satellite cells were absent, but the hypertrophic nerve trunks did show a markedly positive NSE and S-100 immunoreactivity. Two different forms of aganglionic segment were present. One was the middle aganglionic segment of long segment aganglionosis which was almost completely dennervated. In the other type, there were several NSE positive nerve fibers in the muscularis propria of both the aganglionic segment of short segment aganglionosis and the distal aganglionic segment of long segment aganglionosis. These latter two aganglionic segments seemed to be innervated by extrinsic nerves.

S-100 protein-positive Langerhans cells in various human lung cancers, especially in peripheral adenocarcinomas.

Abstract: The appearance of S-100 protein-positive Langerhans cells was studied in 90 cases of various lung cancers by an immunohistochemical method. S-100 protein-positive dendritic cells were frequently observed in many adenocarcinomas, especially in those subclassified as bronchiolar cell or type II alveolar cell type. However, no S-100 protein-positive cells were found in "goblet cell type" adenocarcinoma. In some cases of squamous cell carcinoma and large cell carcinoma, these dendritic cells were also observed though they were fewer in number. In all cases of small cell carcinoma, however, S-100 protein-positive dendritic cells were rare. Electron microscopic study of two adenocarcinomas clearly demonstrated many Birbeck granules in the cytoplasm of S-100 protein-positive dendritic cells and confirmed that S-100 protein-positive cells in lung cancer were identical with Langerhans cells.

The significance of giant cells in human testicular seminomas. A clinico-pathological study.

Abstract: In order to study the nature and significance of various giant cells encountered in seminomatous tumors of the testis, we reviewed the morphology of 243 consecutive pure seminomas and 107 combined (mixed) tumors, as well as the long term clinical follow-up in 26 patients. Giant cells were grouped into histiocytic or neoplastic ones and the latter subtyped according to morphologic and immunocytochemical characteristics. Neoplastic giant cells were found in 34.6% of all pure seminomas and in 11.2% of all combined tumors, i.e. twice as often as histiocytic giant cells in either tumor group. The various types of neoplastic giant cells were found alone or in combinations with other types. Giant cells capable of elaborating B-HCG were seen in 19.3% of all pure seminomas and in 9.3% of seminomatous components of combined tumors. These incidences argue strongly against a trophoblastic element infiltrating a seminoma from a concomitant occult choriocarcinomatous focus. Large mononuclear giant cells, seen in spermatocytic seminomas, were observed in 15.6% of all pure seminomas, particularly in combination with B-HCG producing giant cells. Another type, characterized by marginated nuclei and eosinophilic cytoplasm were invariably part of a mononuclear cell population of similar features and encountered focally in 9.1% of all pure seminomas. Clinical follow-up, particularly in cases with B-HCG positive giant cells, revealed that treatment as for conventional seminomas at an early stage at least is followed by an excellent course.

Ultrastructural characterisation of the proliferative (stem?) cells within the parenchyma of the normal "resting" breast.

Abstract: In this study the proliferative (stem?) cells within the parenchyma of the normal "resting" breast were characterised by the ultrastructural examination of 60 mitotic cells. The parenchyma consists of epithelial and myoepithelial cells plus a few intraepithelial lymphocytes and macrophages. The majority of mitotic cells were randomly distributed throughout the lobules with a few present in ducts. In all cases the cells were identified as luminally positioned polarised epithelial cells. The proliferating cells had similar cytoplasmic features and were indistinguishable from adjacent interphase epithelial cells. No evidence was found for the division of subluminal epithelial or myoepithelial cells. These observations would be consistent with a single cell type giving rise to both epithelial and myoepithelial cells.

Antibodies to cytokeratin and vimentin in testicular tumour diagnosis

Abstract: Thirteen primary and metastatic testicular germ cell tumours, including classical and anaplastic seminomas, and non-seminomatous testicular tumours were examined for their intermediate filament protein (IFP) types. The seminomas were shown to react with a monoclonal and a polyclonal antibody to bovine lens vimentin, while non-seminomatous germ cell tumours were strongly positive for a polyclonal and a monoclonal antibody to cytokeratin.