Premalignant epithelial lesions of the gall-bladder.
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Biomedical subjects
Publications and source records attributed to M N Walters.
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Pleuropulmonary rheumatoid nodules were diagnosed histologically in six patients of whom five were known to have rheumatoid arthritis; the pulmonary lesion preceded the development of arthritis in the sixth patient. Pulmonary lesions are commonly found in patients with rheumatoid arthritis. These lesions are either non-specific (effusions, pleurisy, fibrosis, arteritis and obliterative bronchiolitis) or the specific necrobiotic nodules that constitute Caplan's syndrome in association with pneumoconiosis. The necrobiotic nodules are usually pleural or subpleural and rarely occur in the bronchial tree. Pulmonary necrobiotic nodules can appear before, coincident with, or after the onset of arthritis. It is essential to distinguish these lesions from infections or neoplasia.
Rheumatoid nodules in the heart are unusual specific manifestations of rheumatoid arthritis. This paper describes three cases in which these nodules were found at necropsy. The patients were women with long histories of rheumatoid arthritis, two of whom had significant but unexplained congestive cardiac failure. The rheumatoid nodules were present in the patients' myocardium and in one patient's pericardium. We suggest that in patients with rheumatoid arthritis with severe but unexplained cardiac failure, the possibility of rheumatoid nodules in the heart should be considered.
One hundred and twenty gall-bladders obtained at cholecystectomy for gall bladder diseases formed the basis of a prospective study of premalignant epithelial lesions. Six cases displayed abnormal mucosa (5%); 4 had atypical hyperplasia (dysplasia) and 2 gall-bladders had carcinoma-in-situ; all were associated with chronic cholecystitis and lithiasis. These changes are considered premalignant and are probably precursors of gall-bladder carcinoma. It is impossible to predict which patient with chronic gall-bladder disease is likely to harbour premalignant epithelial changes. In any event, thorough histological examination of all gall bladders removed surgically is more than justified.
A case of adenoid-cystic carcinoma of the prostate is presented. The differential diagnosis and a brief discussion of the possible histogenesis is presented.
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We report here the cases of five patients with primary malignant lymphoma of the brain; all died and a necropsy was performed in each case. Although these lymphomas remain localized, their prognosis is worse than that of lymphomas arising in any other site. Our five cases confirmed the reported natural history of this lesion as a highly malignant neoplasm. There was a discrepancy between the macroscopic appearance of the new growth and its microscopic extent; and the extensive infiltration of the surrounding tissue was not always detected by CT scan. Although primary malignant lymphomas of the brain are radiosensitive and radiotherapy can prolong life, careful clinical judgment is necessary to assess the desirability of the poor quality of life that may follow. Patients with severe intellectual impairment may receive no benefit from aggressive radiotherapy.
Fine needle aspiration cytology was performed in 19 mediastinal lesions. Of seven malignant neoplasms six were correctly diagnosed as malignant and in five of these accurate tumor classification was possible. Of the 12 benign lesions only four cases, all thymomas, could be diagnosed cytologically. No false-positive diagnoses of malignancy were made. The only complication of the procedure was minor pneumothorax in two patients. In five cases the use of the technique spared the patient from more invasive diagnostic procedures; in several others, valuable information was obtained prior to surgery.
Primary linitis plastica type carcinoma of the urinary bladder in a sixty-one-year-old man is described. Only 2 other cases have been reported in the English medical literature.
The cytochemical profile of activated mesothelial cells differs from resting cells. The reaction products of enzymes associated with oxidative mechanisms of cell respiration were easily displayed in activated mesothelial cells; in resting mesothelial cells, only enzymes of the pentose pathway were readily demonstrable. Acid hydrolases were detected in greater quantity than in resting cells, possibly reflecting an increased potential for endocytosis. In addition, the cytochemical assays indicated increased Golgi activity was reflected by the demonstration of thiamine pyrophosphatase, while the content of ribonucleic acid was also increased. These cytochemical features compare well with the ultrastructure of active mesothelial cells which possess abundant ergastoplasm and a well-developed Golgi apparatus. In comparison with peritoneal macrophages, activated mesothelial cells differ mainly in the quantity of reaction product, there being more in macrophages. The results were significantly different only in the demonstration of lipids which were never found in mesothelial cells, but were invariably present in macrophages. It is still unclear whether the acid mucopolysaccharide hyaluronic acid is produced by or merely transported through the mesothelium from the subserosal site.
Linitis Plastica type of carcinoma can arise primarily in the colon or rectum. Fifty-two cases have been reported in the English medical literature over a 50-yr period. Two new cases are described. One patient had primary linitis plastica of the ascending colon, the other being in the rectum. Both patients died of widespread malignancy within 10 mth of diagnosis, the fate of most of the reported cases. This rare manifestation of colo-rectal carcinoma carries an ominous prognosis.
Three cases of nodular lymphomas with cytoplasmic inclusions were studied histologically, histochemically and immunocytochemically, and ultrastructurally. One case had Russell body-like inclusions, another had needle-like inclusions not previously reported, while the last showed cells with cytoplasmic vacuoles. Two of the cases were followed to necropsy. New observations are described and the available literature is reviewed.
The origins, nature, and reactions of the mesothelium have intrigued investigators for over 100 years. Recently, the use of sophisticated techniques has clarified earlier impressions of its development, structure, and function. The structure of mesothelium reflects its functional properties, its long slender microvilli entrapping a layer of glycosoaminoglycans, providing a frictionless free surface between the parietal and visceral serosa. Transport requirements are met by various surface modifications and both inter- and intra-cellular mechanisms occur. The presence of stomatal openings in the mesothelial membrane has been established, and they may have a major role to play in the movement of cells to and from the serosal cavities. In addition, mesothelial cells can respond to situations of increased functional demand and during the course of inflammation, the mesothelium's fibrinolytic properties are of major importance in preventing the formation of adhesions and the enhancement of healing. Of all the unanswered questions the most significant is the nature, localization, and potentialities of mesothelial precursors. A mesodermal origin is readily acknowledged, but the healing process of damaged mesothelium is less clear. It seems probable that "mature" mesothelium is one source of cell renewal, but mesenchymal cells located in the submesothelial serosa are also strong contenders. Neoplastic mesothelium can adopt a spectrum of histological appearances, reflecting its mesodermal origins. In fact, overacceptance of this concept has erroneously led to the classification of other neoplasms arising in the serosal area as mesotheliomas. Although the ocogenic sequence is still obscure, asbestos is recognized as the major etiologic agent in malignant mesotheliomas. In 1955, Hartwell described differing impressions of the peritoneum as seen through the eyes of an anatomist, an histologist, and a surgeon. In this review on the mesothelium we have attempted to unravel some of its complexities as viewed by embryologists, electronmicroscopists, cell biologists, pathologists, and oncologists.
To overcome some of the difficulties encountered in studying single layers of mesothelial cells, a battery of techniques was investigated, assessed, and modified. It was found that two main methods were of value: cell monolayers and surface sections. Imprint monolayers on slides coated with 3% gelatin were considered to provide the optimal imprint for cell kinetics and cytochemical assays at room temperature. On the other hand, slides coated with agar were more satisfactory for cytochemical techniques performed at 37 degrees C. The cell-deposit techniques were excellent for studying mesothelial cells in suspension. Investigation of cultured cells was best achieved by the use of a cell-mat on coverglasses for cytochemistry, while the base of the culture vessel with its own cell-mat monolayer was best for kinetic studies. This investigation demonstrated that maximum information is only gained by employing several different techniques. It also indicates which of these will be of greatest value in assessing any one particular aspect of mesothelial pathobiology.
Cytochemical investigations of the resting mesothelial cells of rats are reported. The study was performed on imprint monolayers obtained from various serosal surfaces by using 3% gelatin and 1% agar-coated microscopic slides. We found only a small amount of reaction product in mesothelial cells after cytochemical demonstration of those enzymes associated with oxidative respiration; however, abundant reaction product was found when the enzymes associated with the pentose phosphate path were sought. These findings suggest that this latter respiratory mechanism may play an active role in resting mesothelial cell respiration. Enzymes associated with cell membranes such as sodium and potassium dependent ATPase and 5' nucleotidase were readily found. The "resting" mesothelial cell also had demonstrable amounts of glycogen and RNA. It is concluded that despite the morphological suggestions that the resting mesothelium is not very active metabolically (Cascarano, 1964), its histochemical profile provides good evidence of a diverse range of functional and metabolic processes. The finding of similar cytochemical profiles, irrespective of the anatomical site of the mesothelial cell sample, is considered to give credence to the concept of the mesothelium as an entity.
Multinucleated giant cells are commonly found in a wide variety of inflammatory reactions. They are formed at sites of tissue injury by fusion of freshly exuded monocytes, the rate of fusion being dependent on a range of extracellular and intracellular factors. Electron miscroscopy shows that the pooled components of the fused monocytes are not randomly dispersed in the syncytium, but are highly reorganized into a functioning unit. In addition, histochemical and biochemical profiles of cell populations containing these polykarya display a range of metabolic activities, including DNA synthesis, which, on occasions, is followed by successful mitotic division and the formation of polyploid daughter cells. Fusion results in the loss of some surface receptors which in turn interferes with the phagocytic performance of polykarya, which is generally less pronounced than their mononuclear precurses. In addition, polykarya are not as actively motile as macrophages although phenomena of contact inhibition are less obvious. On the other hand, the multinucleate giant cells display prominent exocytosis which may aid in the degradation of extracellular material. The properties of macrophage polykarya contrast with macrophage homokarya produced in vitro. The latter are actively phagocytic, do not synthesize DNA, and have a longer half-life than the syncytia produced in chronic inflammatory reactions. It may well be that the polykarya in such reactions are not true homokarya.
The interaction of mononuclear phagocytes with Cryptococcus neoformans was examined in vitro and in vivo using ultrastructural techniques. Immune serum roughens the surface of the yeast and in the first 2 hr, increases the number of organisms attaching to the macrophage surface, as well as the number of contacts between individual yeasts and the phagocyte. Contact is established by means of thin filopodia and cytoplasmic flaps. During the next few days the macrophages increase in size, and, by intimate apposition of their contiguous cell surfaces, a cellular barrier surrounds the now enclosed yeast. These events are accompanied by thinning of fungal capsule, degradation of the enclosed cryptococcus, and the formation of macrophage polykaryons. Electron cytochemical techniques for peroxidase reveal that these multinucleated cells are formed predominantly by the fusion of stimulated macrophages. Destruction of the enclosed yeast probably results from the secretion of various agents by the surrounding cells.
Administration of levan to mice and rats inhibited the passage of intravenously injected trypan blue into the area of skin injected with histamine. In the mouse, the optimal dose of levan was about 5 mg/25 g body weight; higher doses, on the other hand, enhanced diffusion. In the rat, the inhibitory effect was directly related to the dose of levan, the optimal dose being five times higher than for mice. Treatment of rats with levan caused a marked reduction in the uptake and transport of colloidal carbon. In normal and histamine- or turpentine-injected cremaster muscles, treatment with levan prevented carbon from being adsorbed and endocytosed by the endothelial cells. Levan itself was frequently attached to the lumenal surface of endothelial cells, or less frequently was enclosed within pinocytic vesicles. Occasionally, transport across the interendothelial junction was also seen, but the impression gained was that the frequency and extent of patent junctions were reduced in animals receiving phlogistic stimuli and treated with levan. Carbon particles were generally aggregated in the central zone of vessels and were seldom seen near the endothelial cells, within endothelial cells or within any open junctions, presumably because of the coating effect of levan. With partly depolymerised levan, carbon particles were found in endothelial cells and intercellular spaces, but at lower concentrations than in non-levanised control animals. It is suggested that levan acts by altering the rheologic patterns in the microcirculation, by modifying the surface of endothelial cells and by influencing their behaviour, and, finally, by changing the constitution of the ground substance and basement lamina.