PubMed Health⌕ Search

Biomedical subjects

M Laitio

Publications and source records attributed to M Laitio.

At least 19 recordsLinked to original sources

Histogenesis of epithelial neoplasms of human gallbladder I. Dysplasia.

In order to find a relationship between normal gallbladder epithelium and dysplastic epithelium, histological and histochemical examinations were made on gallbladder specimens obtained from cholecystetomies and special attention was paid to the relationship of the different metaplasias. Epithelial pseudostratification increases in mitotic figures and hyperchromatism accord well with the degrees of dysplasia of surface epithelium. The relationship of the ratio of cell and nuclear size and complexity of glandular branching is more meaningful in degrees of dysplasia of glandular epithelium. Epithelial dysplasia in the surface and glandular epithelium was divided into three types: mild, moderate and severe. This classification was made on the basis of specimens containing dysplasia selected from an extensive gallbladder material. The frequency of dysplasias of different degrees was clarified in 71 cholecystectomia gallbladders. No dysplastic changes were demonstrated in 47 gallbladders (66.2%), and in 10 of these metaplasia was present, 24 gallbladders (33.8%) exhibited dysplastic changes; metaplasia was present in 20 cases (83.3%) and in 14 (58.3%) in the dysplastic region. Severe dysplasia was present only in one case, moderate in 6 and mild dysplasia alone in 17 cases. Dysplasia was found in glands only in 3 cases. In dysplastic epithelium, the mucin reaction was similar to that in the metaplastic epithelium. It contained mainly nonsulphated acid mucin and neutral mucin. With gradually increasing degree of dysplasia the amount of mucin. With gradually increasing degree of dysplasia the amount of mucin clearly decreased. The present results indicate that dysplasia often develops in metaplastic epithelium.

Adult↗

Histogenesis of epithelial neoplasms of human gallbladder II. Classification of carcinoma on the basis of morphological features.

The material consisted of 83 gallbladders with primary carcinoma. Non-malignant bordering mucosa was present in 37 specimens and in 34 of these (92%) it was metaplastic, mostly (78.4%) of antral type. In all but one case the bordering epithelium contained dyplasias of different degrees and thus the dysplasia had manifested in metaplastic epithelium. According to their degree of differentiation, the carcinomas were divided in three groups. In groups 1 and 2 the structure was intestinal. Group 1, which had the highest degree of differentiation, contained papillary and glandular structures. Group 2 contained similar glandular structures but, unlike group 1, no goblet and no enterochromaffin cells. In group 3 (anaplastic carcinomas) the mode of growth was infiltrative or solid. The amount of mucin decreased with the degree of differentiation. Histochemically, there were no differences between the groups, but the mucin was mainly non-sulphated acid mucin as in the metaplastic and dysplastic areas surrounding the tumour, thus differing from the normal gallbladder epithelium containing sulphated acid mucin. In 52 cases it was possible to investigate the superficial part of the tumour. The carcinoma structure was of a high degree of differentiation (group 1) in 29 (55.8%) cases, which all had structures of group 2 in the deeper layers. These results indicate that the structure of the carcinoma is not permanent, it dedifferentiates at the deeper invasive layers. In only two cases (3.8%) was the anaplastic structure of group 3 already on the surface without the intermediate stages of groups 1 and 2.

Adenocarcinoma↗

Carcinoma of extrahepatic bile ducts. A histopathologic study.

The material consisted of 44 primary carcinomas of the extrahepatic bile ducts. It was possible to investigate the border region in 15 specimens, 12 (80%) of which showed metaplastic changes. All of these specimens had dysplastic changes in superficial epithelium, often multifocal: mild dysplasia in 91% of cases, moderate in 82% and severe in 45%; and dysplastic changes in the lower glandular epithelium: mild dysplasia in 57% of cases, moderate in 57% and severe in 14%. Of the 44 carcinomas, 16 were papillary adenocarcinomas and 28 gland-forming adenocarcinomas. The material included no mucinous carcinoma nor adenosquamous carcinoma or squamous cell carcinoma. According to their degree of differentiation, the tumours were graded in three groups. The criteria were the same as in the study of carcinoma of the gallbladder (Laitio, manuscript). The luminal surface of the tumour was present in 31 cases. In 17 (54.8%) cases, the structure was intestinal containing goblet cells (group I). In 18 of the 31 cases dedifferentation was apparent in the deeper parts. In the superficial parts there was no anaplastic carcinoma (group III). The histochemical results was similar to that in the gallbladder. The morphologically normal epithelium contained sulphated mucin. The metaplastic and the tumorous areas contained mainly non-sulphated acid mucin and neutral mucin. These results show that the cancerogenesis was similar to that in the gallbladder. Dysplastic changes develop in metaplastic cells and become malignant. Often, the forming of the intestinal tumour structure, as it undergoes changes, finally attains an anaplastic structure.

Adenocarcinoma↗

Morphology and histochemistry of non-tumorous gallbladder epithelium. A series of 103 cases.

One hundred and three gallbladders were excised from 81 female and 22 male patients. Different non-tumorous morphologic and histochemical changes and their frequency were studied in these gallbladders and in their various components. Histochemical methods were used to visualize sulphated, non-sulphated acid, and neutral mucins. Sulphated mucin predominated in normal columnar epithelium and in the glands of the neck region, whereas non-sulphated acid mucin and neutral mucin predominated in goblet cell areas, in superficial gastric-type epithelial areas and in antral-type glands. Goblet cells were present in 67 specimens, enterochromaffin cells in 42, superficial gastric-type epithelium in 16, antral-type glands in 40, antral-type mucosa in 8 and intestinal-type mucosa in one specimen. Goblet cells, enterochromaffin cells, and gastric surface epithelium columns appeared initially in the surface portions of the folds. No relationship was established between the degree of metaplasia, the age of the patient, the duration of symptons, and the severity of illness.

Adolescent↗

Hexosamine-containing macromolecules in human colon carcinomas.

Normal, transitional, and carcinoma areas of five colons resected for carcinoma were examined morphologically, histochemically, and biochemically. The transitional area contained a larger amount of non-sulphated acid mucin than the normal mucosa as verified histochemically. Normal mucosa contained mainly sulphated mucin. The hexosamine-containing macromolecules present in different areas were isolated and characterized. They were divided into the following groups: 1) acid glycosaminoglycans, 2) high-molecular-weight glycopeptides, and 3) low-molecular weight glycopeptides. The concentration of the total hexosamine-containing material was in the carcinoma area twice as high as in normal areas. Acid glycosaminoglycans were identified as hyaluronate, heparan sulphate, dermatan sulphate, and chondroitin 4-(6)-sulphate. Their concentraitons were found to increase from normal to transitional and from transitional to carcinoma areas. The high-molecular-weight glycopeptide was composed of fucose, galactose, glucosamine, galactosamine, sialic acid, and variable amounts of sulphate. The sulphation degree of the glycopeptide was higher in normal mucosa than in transitional or carcinoma areas: The low-molecular-weight glycopeptides consisted of about a half of the total hexosamine-containing substances. The concentration of saline-insoluble fraction of the low-molecular-weight glycopeptides was in transitional areas about two times, and in carcinoma areas about four times, higher than in normal mucosa.

Adenocarcinoma↗

Intestinal, gastric body- and antral-type mucosal metaplasia in the gallbladder.

The material consisted of two intestinal, one gastric body-type and 14 antral-type cases of mucosal metaplasia in the gallbladder. Outside the mucosal areas mentioned, the epithelium of the gallbladder had undergone great changes. It usually consisted of goblet cells, enterochromaffin cells, superficial gastric-type epithelial islands and antral-type glands. Extensive areas contained non-sulphated acid mucin and neutral mucin. The areas of normal gallbladder epithelium were small.

Gallbladder↗

Lamellated osmiophilic bodies in mouse gallbladder epithelium.

Mouse gallbladder epithelium was studied in the electron microscope after glutaraldehyde and osmium tetroxide fixation and Epon embedding. Special attention was paid to dense cytoplasmic bodies. Heterogeneous dense bodies with osmiophilic and loose granular components were identified. Many of these bodies consisted of lamellated osmiophilic structures, similar to the phospholipid bodies of the large alveolar (type II) cells of the mammalian lung. The dense bodies containing the lamellar structures were membrane-limited and 0.5-1.0 mum in diameter. They were located in the supranuclear cytoplasma and were often closely associated with the Golgi apparatus. Acid phosphatase activity was demonstrated within these bodies and in some of the Golgi vacuoles. The contents were disposed in concentric lamellar osmiophilic structures, sometimes appearing as scroll-like configurations. These morphological findings were interpreted as indication of these presence of phosphlipid absorbed from the gallbladder lumen and stored in phagosomes in the central cytoplasm of the gallbladder epithelial cells.

Acid Phosphatase↗

Early carcinoma of the gallbladder.

The material consisted of 12 gallbladder carcinomas, all in their early phases. Ten of the patients were female, two were male. The mean age of the patients was 65 years, and the mean lifetime after operation was as short as five months. The purpose of this study was to obtain further information on the significance of metaplastic mucosal islands in the histogenesis of gallbladder carcinomas by investigating incipient carcinomas and the conditions of the adjacent mucosa. The investigation revealed goblet cells and enterochromaffin cells outside the tumour in four specimens, antral-type glands in ten specimens, gastric-type superficial epithelial islands in all twelve specimens. In eight cases there was an antral-type mucosal island outside the tumour. In six specimens the tumour was found to border on antral-type mucosa. The structure of the tumour was papillary in ten cases, and mucinous in two. The tumorous epithelium showed in all specimens focal intestinal-type areas. Six tumours displayed goblet cells, and enterochromaffin cells were present in four tumours. The two mucinous tumours seemed to have originated in the glands of the antral-type mucosa extending toward the serosal surface of the gallbladder wall. This study supports the theory suggesting a significance of metaplasia in the histogenesis of gallbladder tumours.

Adenocarcinoma, Mucinous↗

Intestinal-type carcinoma of gallbladder. A histochemical and immunologic study.

Two intestinal carcinomas of the gallbladder are presented. In both carcinomas the structure was papillary in superficial parts; the deeper ones also tended to an adenomatous structure. One of the tumors was bordered by a mucosa, with both intestinal- and antral-type metaplastic islands. The tumor was mainly a typical papilloma with malignant degeneration and infiltrative growth. The intestinal structure was morphologically clear in the papillary area of both carcinomas, but not distinct in the invasive part of the tumor. In both tumors, goblet cells and columnar cells with a distinct brush border were noted. Histochemical and immunologic methods were used in the identification of the glycoproteins of the tumor cells. With both methods the intestinal character of the tumor could be shown. A positive fluorescence was achieved with an intestinal antiserum in well-differentiated tumorous areas containing goblet cells, as well as in the intestinal metaplastic areas. In the same areas the gallbladder-specific antigen was negative. The antiserum isolated from the normal gastric mucosa and corresponding to neutral glycoprotein gave a positive fluorescence only in the nontumorous metaplastic gastric superficial-type epithelium and in the metaplastic antral-type glands.

Aged↗

Goblet cells, enterochromaffin cells, superficial gastric-type epithelium and antral-type glands in the gallbladder.

From a material derived from routine investigations, 40 gallbladder specimens were selected in which metaplastic cells had been observed. All the cholecystectomies were performed for gallstones. Of the patients 6 were male and 34 female. The mean age was 51.2 years. 36 specimens revealed goblet cells, enterochromaffin cells were found in 22, antral-type (pseudopyloric) glands in 23 and islands of gastric surface epithelium in 15 specimens. Histochemical methods to visualize sulphated, non-sulphated acid and neutral mucins were used. Ordinary gallbladder epithelium showed a predominance of sulphated mucosubstance. Sporadic goblet cells usually occurred in so-called goblet cell areas which, if small, were located in the tops of folds and only when larger also in the deeper parts of folds. As the goblet cell area enlarged, the relative proportion of sulphated mucin diminished and correspondingly non-sulphated acid mucin increased, while neutral mucin was noted both in the goblet cells and in the intervening columnar cells. In 20 specimens there were enterochromaffin cells in the goblet cell areas while only 2 specimens revealed enterochromaffin cells outside the goblet cell area. The glands outside the neck region of the gallbladder resembled gastric antral glands in their general architecture and in the appearance of individual cells. A part from frequent enterochromaffin cells (in 12 specimens) the glands are composed of mucous cells. The glandular cells contained sulphated mucin, non-sulphated acid and neutral mucin chiefly in the peripheral parts of glandular cells. In the gallbladders there were numerous abnormalities in some areas: heavy mucous secretion, goblet cells, enterochromaffin cells and superficial gastric-type epithelial spots were seen chiefly in the upper parts of folds, while proliferation of antral-type glands occurred in the basal parts. It is probable that some common pathological factors are responsible for the frequent simultaneous appearance of different types of metaplasia.

Adult↗

An electron microscopic study of intestinal metaplasia in human gallbladder.

Areas of intestinal metaplastic epithelium in gallbladders removed by cholecystectomies performed for gallstones were studied with the electron microscope. Three gallbladders contained areas of goblet cells and endocrine enterochromaffin-like cells and one gallbladder also Paneth cells. The goblet cells contained mucin granules of slightly variable size and shape and relatively great electron lucency. The intervening columnar epithelial cells contained various amounts of electron-lucent mucin granules. The round or oval enterochromaffin-like cells rested on the basement membrane, and in these cells the small, round, electron-opaque secretory granules were located in the infranuclear region. The supranuclear cytoplasm of the Paneth cells in the intestinalized epithelium contained typical large, round secretory granules. The fine structures of the various cells in the metaplastic epithelium bore resemblance to those of the cells in the intestinalized stomach mucosa.

Basement Membrane↗

Gland ultrastructure in human gall bladder.

The ultrastructure of two gland cell types in the chronically inflamed human gall bladder is described. The lumina of the glands in the neck region are wide and the gland cells are cuboidal in shape. The nuclei are round and relatively large and there are only a few secretory granules in the scanty cytoplasm. Glands elsewhere resemble those in the pyloric antrum of the stomach in their ultrastructure, and therefore the former may be called "antral type" glands. They contain abundant mucin granules in their cytoplasm and the Golgi apparatus is prominent. There are rather tall irregular microvilli on the apical cell surface and the nuclei are located close to the basal plasma membrane. Enterochromaffin-like cells are to be found in the antral type glands, but not in the glands of the neck region.

Cell Nucleus↗

Ultrastructure of endocrine cells in metaplastic epithelium of human gall bladder.

Two endocrine cell types were found in the metaplastic epithelium of gall bladders removed for gall stones. The endocrine cell type I resembled the EC (enterochromaffin) cell of the normal stomach mucosa. The homogeneous and electron-dense secretory granules were variable in size and shape and mainly located in the sub-nuclear cytoplasm. The endocrine cell type II was similar to the ECL (enterochromaffin-like) cell of the human stomach. The secretory granules were almost exclusively present in a subnuclear location, and were round and homogeneous in size. The secretory material was slightly granular and often there was a clear zone (halo) between the granule core and the limiting membrane. A rich network of microfilaments in the cytoplasm, especially around the nucleus, was typical of the type II endocrine cell. Both cell types were closely related to the basement membrane and the capillaries underneath.

Cholelithiasis↗

Polysaccharides of metaplastic mucosa and carcinoma of the gallbladder.

The polysaccharide composition of the human gallbladder well was studied in carcinomas and metaplastic changes of various degrees, and the results obtained were compared with those for the normal material previously presented (Terho, T., and Laitio, M. Biochim. Biophys. Acta 338: 135, 1974). Elevated amounts of acid connective tissue polysaccharides (heparitin and dermatan sulfates as well as chondroitin 4- or 6-sulfate, or both, could be observed in carinomas. In histochemical stainings it was found that in carcinomas and in the two specimens classified as group III (containing the most extensive metaplastic changes at disposal), the intracellular mucin was mainly neutral or nonsulfated acidic. The amounts of sulfated mucin were relatively insignificant. This mucin polysaccharide material was isolated and its composition was determined. It was observed to be large polysaccharide material was isolated and its composition was determined. It was observed to be large molecular (approximate molecular sizes 1 to 2 times 10-6), and to be composed of fucose, galactose, glucosamine, and galactosamine as well as small amounts of sialic acid. The basic structure of these polysaccharides is thus similar to that of normal sulfated mucin. The almost total absence of acid groups, however, causes the polysaccharide material in question to stain in a manner identical with neutral mucin when investigated with histochemical methods. The carcinomas also contained some sulfomucin; its proportion, however, was small as compared with the amounts of nonsulfated acid and neutral mucin in biochemical characterization. A small molecular polysaccharide fraction, assumed to originate in membrane-bound glycoproteins, was isolated from the insoluble gallbladder tissue residue. The proportion of this fraction was larger in carcinomas than in normal material. This rise as well as the rise in the quantity of acid connective tissue polysaccharides is presumably due to the large number of cells in the carcinoma tissue as well as to fibrosis.

Adenocarcinoma↗