Histopathological differences in the development of small intestinal metaplasia between antrum and body of stomach

This study used mucin immunohistochemistry to investigate differences in the properties of intestinal metaplasia between the antrum and body of the stomach in 28 resected specimens. Intestinal metaplasia was classified as: (1) small intestinal metaplasia (SIM) with a tubule, including CD10-positive brush border on a background of MUC5AC-/ HGM-negative cells; or (2) goblet cell metaplasia (GCM) with MUC2-positive and CD10-negative cells. In the antrum, frequencies of SIM and GCM were nearly equal irrespective of metaplasia grade. Frequency and length of remnant pyloric gland for SIM were significantly greater in the antrum than in the body. In the proliferative zone, there existed a lower level in SIM than in non-intestinalized tubules. These findings suggest that the proliferative zone shifts from the neck zone toward the bottom of the tubule during the SIM process in the antrum. In the body, however, the grade of SIM grade was significantly higher than that of GCM. The proliferative zone was located higher in the fundic gland, pseudopyloric gland and SIM, in that order. Almost all remnant pyloric glands for SIM were negative for pepsinogen I. These facts indicate that SIM in the body originates in a proliferative zone that shifted downward to an area near the bottom of the tubule, with atrophic pyloric glands originating from pseudopyloric gland metaplasia.     

Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach

We have proposed that intestinal metaplasia (IM) of the human stomach be divided into two types on the basis of cell differentiation status: a gastric and intestinal (GI) mixed type and a solely intestinal (I) type. In the GI mixed type, gastric (foveolar epithelial and pyloric gland cells) and intestinal (goblet, intestinal absorptive, and Paneth cells) phenotype cells coexist in the same intestinalized gastric glands in various combinations and degrees. Consequently, intestinalized gastric glands are hybrids. Although we have described the rare appearance of Paneth-like cells in pyloric glands of GI mixed-type IM, the absence of an appropriate Paneth cell marker leaves room for doubt as to their true character. The purpose of this study was to clearly identify Paneth cells in pyloric glands in IM lesions using a new Paneth cell marker, a polyclonal antibody human defensin (HD)-5, raised against HD-5, which is included in granules of Paneth cells. A total of 105 gastric samples (4 biopsy and 101 surgical resected specimens) were examined. In only nine cases (8.6%), the antibody allowed demonstration of Paneth cells in pyloric glands in GI mixed-type IM, confirming our previous finding. Analysis of the proliferative cell (P) zone indicated that a common stem cell might generate both GI phenotype cells by upward and downward migration. No Paneth cells were found above the P zone. The results suggest that the stem cells show abnormal cell differentiation in IM lesions but preserve their normal direction of migration.     

Tritiated thymidine autoradiographic study on histogenesis and spreading of intestinal metaplasia in human stomach.

The non-diseased portions of the antral mucosa of patients suffering from gastric cancer or ulcer were biopsied. The biopsy specimens were then labelled with 3H-thymidine in vitro, and distribution of the labelled epithelial cells in the normal pyloric and in the intestinalized mucosa was studied with autoradiography, and modes of histogenesis and spreading of the intestinal metaplasia were studied, and kinetic characteristics of the intestinalized mucosa were discussed. In the normal pyloric mucosa, the labelled cells were confined to the isthmus region (the middle one-third level of the mucosa), indicating that the surface epithelial and the pyloric glandular cells are normally replaced from the isthmus region. On the other hand, a zone of the labelled cells was found at the lower one-third level in the intestinalized mucosa. The absorptive and the goblet cells in the intestinalized mucosa appear to be renewed by about 70 hours in a fashion similar to that of the small intestine. Microscopic and autoradiographic analysis of the antral mucosa in the course of intestinalization indicates that the intestinal metaplasia begins in the isthmus region of the pyloric glandular tubules of an intact mucosa unaffected by gross injury through transformation of the generative cells from a pyloric to an intestinal pattern. This permits the pyloric lining cells to be replaced with intestinal villous cells and also permits the generative cell zone of the intestinal tubules to shift from the isthmus to the base of the gland until the process is complete. The downward shift of the intestinal tubules occurs in a framework of one of the branched pyloric glands and other glands disappear, resulting in a change of mucosal architectures of the antrum from a branched to a simple tubular gland. The intestinal metaplasia spreads in the mucosa through multi-focal (and sporadical) transformation of the neck generative cells in individual glandular tubules.     

Pyloric metaplasia,pseudopyloric metaplasia,ulcer‐associated cell lineage and spasmolytic polypeptide‐expressing metaplasia: reparative lineages in the gastrointestinal mucosa

The gastrointestinal mucosae provide a critical barrier between the external and internal milieu. Thus, damage to the mucosa requires an immediate response to provide appropriate wound closure and healing. Metaplastic lineages with phenotypes similar to the mucous glands of the distal stomach or Brunner's glands have been associated with various injurious scenarios in the stomach, small bowel, and colon. These lineages have been assigned various names including pyloric metaplasia, pseudopyloric metaplasia, ulcer‐associated cell lineage (UACL), and spasmolytic polypeptide‐expressing metaplasia (SPEM). A re‐examination of the literature on these various forms of mucous cell metaplasia suggests that pyloric‐type mucosal gland lineages may provide a ubiquitous response to mucosal injury throughout the gastrointestinal tract as well as in the pancreas, esophagus, and other mucosal surfaces. While the cellular origin of these putative reparative lineages likely varies in different regions of the gut, their final phenotypes may converge on a pyloric‐type gland dedicated to mucous secretion. In addition to their healing properties in the setting of acute injury, these pyloric‐type lineages may also represent precursors to neoplastic transitions in the face of chronic inflammatory influences. Further investigations are needed to determine how discrete molecular profiles relate to the origin and function of pyloric‐type metaplasias previously described by histological characteristics in multiple epithelial mucosal systems in the setting of acute and chronic damage. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

肠上皮生化,异型增生及胃癌的细胞动力学研究

48 specimens of gastric mucosa, including those of normal mucosa, intestinal metaplasia, atypical hyperplasia and carcinoma, were studied with in vitro 3H-TdR double labeling autoradiographic technique. On the basis of cell kinetics, intestinal metaplasia might be divided into two types: Type A consisted of those cases in which the values of LI, Ts and Tc were approximately closer to those of normal mucosa. The labeling cells appeared in the lower two thirds of the intestinalized glands, including small intestinal type and the complete type of colonic intestinal metaplasia. In type B, the average values of LI were higher. Ts and Tc values approximated those found in carcinoma a. Type B consisted mostly of the incomplete type of colonic intestinal metaplasia. The above evidence suggests that type B intestinal metaplasia is precancerous.     

Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study

The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.     

Six types of intraepithelial vacuoles in the human gastric mucosa

Two types of goblet cells are classically described in the literature as markers of intestinal or colonic metaplasia of the gastric mucosa. In addition to those, four types of vacuolated cells in the gastric mucosa are herein described. One type corresponded to mucus-positive goblet cells (as in classical intestinal metaplasia) but containing in addition neuroendocrine granules. Another type presented vacuolated cells with cilia. Many of the ciliated cells had negative mucus reaction. Ciliated metaplastic cells were observed in cystically dilated pyloric glands. Another type was characterized by vacuolated cells without cilia, also in pyloric glands. The latter vacuoles often adopted an infranuclear position. Finally, cells with intraepithelial vacuoles (mucus-negative) centered by a lymphocyte were recorded in foveolar cells. Possible explanations for the occurrence of the type of intraepithelial vacuoles herein described were discussed. The occurrence of various types of intraepithelial vacuoles in the gastric mucosa should be borne in mind in the histological differential diagnosis of intestinal metaplasia in the gastric mucosa in H & E routine examinations.     

Changes in the intermediary glands of the gastric mucosa in peptic ulcer of different localization in morphometric interpretation]

Histologically and morphometrically (by the method of V.A. Samsonov). 80 stomachs resected for peptic ulcers were studied. Intermediary glands without atrophy were found in 16.3% of cases, atrophic changes in 51.2% of cases; in 32.5% of cases they disappeared completely and were substituted mainly by fields of intestinal metaplasia they disappeared completely and were substituted mainly by fields of intestinal metaplasia and pseudopyloric glands. In the atrophic process the number of cells increased in the gastric fossas and decreased in the glands; the gland-fossa epithelial cell index and the ratio of chief and parietal cells decreased. In the epithelial formula of intermediary gland the percentage of secondary and undifferentiated cells increased and that of parietal and particularly chief cells decreased. When the ulcers were localized in the stomach the glands were involved more frequently and extensively than in duodenal ulcers.     

Morphological lesions of the pancreatic ducts. Significance of pyloric gland metaplasia in carcinogenesis of exocrine and endocrine pancreas

Morphological lesions of the pancreatic ducts were studied in 113 control autopsy cases, and 84 cases of primary pancreatic carcinoma. The lesions were classified into pyloric gland metaplasia, focal pseudo-proliferation, goblet cell metaplasia, squamous metaplasia, and atypical proliferation. Diabetes mellitus or glycosuria, alcohol intake, and smoking do not seem to have any close associations with these lesions or pancreatic carcinoma. Pyloric-gland and squamous metaplasias were found at nearly comparable incidences both in control and carcinoma cases, but marked atypical proliferations, which were indistinguishable from carcinoma in situ or intraductal spreading of carcinoma, were more frequently observed in the carcinoma cases. Pyloric gland metaplasia was the most common among the various lesions, and considered to represent nonspecific change of the pancreatic duct. However, it was suggested that some of the metaplastic lesions might be transformed into atypical proliferations and further into carcinoma in situ. The expected latent period from the appearance of in situ lesion to overt pancreatic carcinoma may be a clue to early diagnosis and effective surgical treatment, but possible multiplicity of carcinoma in situ or intraductal spreading of carcinoma even at its early stage will burden further problems on its treatment. On rare occasions, argyrophil cells were found in the pyloric gland metaplasia, and its significance was discussed in relation to the genesis of Zollinger-Ellison tumor.     

A novel subtyping of intestinal metaplasia of the stomach,with special reference to the histochemical characterizations of endocrine cells

Summary Intestinal metaplasia of the stomach was grouped into 3 subtypes (A, B and C) according to the degree of pyloric gland involution which was judged from patterns of paradoxical Concanavalin A staining after Katsuyama and Spicer. The appearance of endocrine cells was investigated with immunohistochemical and silver methods. Type A metaplasia with slightly to moderately atrophic pyloric glands corresponded to the incomplete type in the previous classification, while Type C showing complete disappearance of pyloric glands corresponded to the complete type. Type B with severely atrophic pyloric glands was an intermediate. This subtyping reflects the cell kinetics in the intestinalized mucosa well. Regarding the endocrine cells, their total number varied in the order Type A > Type B > Type C. The selective populations of the endocrine cells including glicentin-containing cells, Grimelius-positive argyrophil cells without argentaffinity and intestinal-type enterochromaffin cells frequently formed hyperplastic foci in the intestinalized areas, where the other gut-type and proper gastric-type endocrine cells were scarcely noted. Immunoreactivity of glucagon or bovine pancreatic polypeptide were occasionally identified in a subpopulation of the glicentin-containing cells.     

A HISTOPATHOLOGICAL STUDY OF DIFFUSE HYPERPLASIA OF GASTRIC ARGYROPHIL CELLS

The present study includes a histopathological and immunohistochemical study of 4 cases of diffuse hyperplasia of gastric argyrophil cells. The mode of proliferation of these cells and the production of hormone by these cells have been documented. The distribution of microacinar nests composed of argyrophil cells was thought to be related to chronic gastritis in which there are atrophy of mucosa and intestinal metaplasia. In the case in which these nests were found only in the corpus ventriculi, there was intestinal metaplasia throughout the stomach. On the other hand, in the case in which these nests appeared only in the pyloric area, atrophy of the mucosa with mild intestinal metaplasia was observed only in the pyloric area. The microacinar nests composed of argyrophil cells were distributed in the deep mucosa at the basal portion of the glands in the area with intestinal metaplasia. Serial sections revealed a sprout composed of argyrophil cells budding from the gland with intestinal metaplastic changes. The sprout buds out from the growth zone of glands with Intestinal metaplasia and then becomes isolated and gives rise to reactive hyperplasia. The peptide hormone contained in these cells differs according to the mucosal environments. Cells containing gastrin were observed in the pyloric area, but not in the corpus ventriculi where there was marked intestinal metaplasia. The cells in this area were assumed to contain other hormones.     

Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of the stomach.

A morphological range of 67 hyperplastic polyps was studied. They included polyps removed endoscopically and polyps found incidentally in resected stomachs with gastric ulcers and cancer. The hyperplastic polyps were essentially composed of cystic foveolae and pyloric type glands, lined by cells identical to those of the normal gastric mucosa. Thirty one polyps contained other cytological elements. In 18, intestinal metaplasia was seen; the tubules were mostly composed of columnar and goblet cells and lacked Paneth cells. In 11 polyps, nine cases of gastric dysplasia and two cases of intestinal dysplasia, dysplastic changes were found. The former consisted of a proliferation of irregularly shaped pits with pleomorphic cuboidal/columnar cells with relatively basophilic cytoplasm. They contained mucigen granules of a gastric type. The latter consisted of atypical pits composed of closely packed, tall columnar and small goblet cells, both resembling adenomatous cells of the colon. In three polyps carcinomas were seen, one of which was an intestinal type adenocarcinoma. In the other two, the cancer cells closely resembled the normal foveolar cells, containing gastric type mucigen granules. They were gastric type adenocarcinomas.     

Complete and incomplete pyloric gland metaplasia of human gallbladder

The features of pyloric gland metaplasia in the gallbladder epithelium were studied by histochemical staining for mucin and the immunoperoxidase method for pepsinogens (Pg) I and II. Pyloric gland metaplasia was found in 48 of 72 gallbladders removed surgically. All the pyloric gland metaplastic cells contained class III mucin demonstrated by paradoxical concanavalin A (Con A) staining. Pyloric gland metaplasia was classified into complete and incomplete types on the basis of the immunohistochemical reactivities of Pgs I and II: The complete type of pyloric gland metaplasia contained neutral mucins and weak Pg I and strong Pg II activities, like normal pyloric gland cells. Almost all specimens of the incomplete type of pyloric gland metaplasia contained acid mucins and were further classified into two types: an incomplete type 1, which had Pg II but no Pg I activity, and an incomplete type 2, which had no Pg I or II activity.     

Metaplastic lesions of the extrahepatic bile ducts: a morphologic and immunohistochemical study.

Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic study of these lesions has not been done. We examined the bile duct mucosa in 42 pancreaticoduodenectomy specimens, 32 with neoplastic lesions and ten with inflammatory lesions of the extrahepatic bile ducts, to assess the prevalence and type of metaplastic lesions. For comparison, the common bile ducts from 10 autopsy cases were reviewed. Twenty of the 42 total cases (48%), 13 of the 32 neoplastic cases (40%), and 7 of the 10 inflammatory cases (70%) had metaplastic changes. Pyloric gland metaplasia was the most common type (16/20 cases; 80%), whereas intestinal metaplasia was seen in 1/20 cases (5%). A combination of pyloric gland and intestinal metaplasia occurred in 2/20 cases (10%), and squamous metaplasia plus the above-mentioned two types of metaplasia was seen in 1/20 cases (5%). None of the normal common bile ducts obtained from ten autopsies had metaplastic changes. Endocrine cells were identified in nine (56%) of 17 metaplastic lesions. In contrast, endocrine cells within the intramural glands were seen in only 2 of the 10 normal common bile ducts. Although a significant proportion of carcinomas (6/13 cases) was in close proximity to areas of metaplasia, we were unable to find dysplastic foci within the metaplastic glands or the metaplastic surface epithelium. Reactive atypical cells involved the surface biliary epithelium and intramural glands and were associated with inflammation and metaplastic changes. The presence of goblet, mucinous, squamous, and reactive atypical cells in association with hyperplasia of intramural glands in frozen sections or small biopsy specimens may be mistaken for malignancy; hence, recognition of these lesions is of diagnostic importance.     

Concurrent tubulovillous adenoma and transitional cell carcinoma associated with diffuse gastric and intestinal metaplasia of the defunctioned ureter

Villous adenoma is a common lesion of the gastrointestinal tract, but it is rare in the ureter. Thus, as far as we know, only one case limited to this location has been described. Intestinal metaplasia of the urothelium is not rare. However, only one case of gastric metaplasia with pseudopyloric glands has been described in the literature. We here report in detail on a tubulovillous adenoma of the ureter associated with diffuse gastric and intestinal metaplasia and a concurrent primary, solid, high grade transitional cell carcinoma, with extensive clear cell change, in a 56-year-old male patient. He had undergone a left nephrectomy for renal tuberculosis twenty years earlier, and the lesions developed in the ureteric stump. To the best of our knowledge, such a combination of lesions has not been reported previously either in the ureter or in the rest of the urinary tract. The coexistence of diverse lesions in our case might represent the pluripotentiality of the urothelium in association with chronic inflammation and neoplastic induction. The present report also emphasizes the metaplastic and malignant potential of a defunctioned urothelial structure. This case is of particular interest, because these coexistent lesions arose simultaneously with an anatomically separate adenocarcinoma of the rectum (Dukes' B). The patient died 76 days after admission. The dismal prognosis of our case was determined by the advanced anatomical stage and the histological high grade of the transitional cell carcinoma of the ureter.     

Gastric and intestinal mixed and solely intestinal types of intestinal metaplasia in the human stomach

To generate a novel understanding of Intestinal metaplasia (IM) on the basis of cellular differentiation status, a total of 132 gastric surgical specimens were studied using gastric and small intestinal cell markers by much histochemical and Immunohistochemical techniques. The cases were divided into two types: (i) gastric and intestinal (GI) mixed type; and (ii) solely intestinal (I) type, with the reference to the presence of gastric and/or intestinal cell markers. The GI mixed type was subdivided into six subtypes: (i) a subtype consisting of surface mucous (Su), pyloric gland (Py), Intestinal absorptive (Ab), and goblet (Go) cells, but lacking Paneth (Pa) cells, GI(Pa-); (ii) a GI(Pa-) subtype without Py cells, GI(Py-, Pa-); (iii) a GI(Pa-) subtype without Su cells, GI(Su-, Pa-); (iv) a GI(Su-, Pa-) subtype with Pa cells, GI(Su-, Pa+); (v) a Gi(Pa-) subtype with Pa cells, GI(Pa+); and (vi) a GI(Pa+) subtype without Py cells, GI(–, Pa+).The I type was subdivided Into: (I) a subtype consisting of cells with Ab and Go cells, I(Pa-); and (ii) a I(Pa-) subtype with Paneth cells, I(Pa+). The GI mixed subtypes, except for the GI(Py-, Pa-) and GI(Py-, Pa+), were characterized by Intestinalized gastric plts connected with underlying pyloric glands. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) revealed a common prolifemtive cell zone between the two. The GI mixed type, especially the GI(Pa-) subtype, predominated in the pyloric mucose, while the I type was most frequent In the fundle region, suggesting that the pathogenesis of IM differs between these two locations. The results of the study confirm that IM is an abnormal and unstable differentiation status between the stomach and small Intestine.     

Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomach

Intestinal metaplasia (IM) in the human stomach has previously been classified into a gastric and intestinal mixed (GI-IM) and a solely intestinal phenotype (I-IM). The phenotypes of mucous and endocrine cells were evaluated in 3034 glandular ducts associated with chronic gastritis. In the pyloric region, the relative expression of gastric endocrine cell markers, such as gastrin and somatostatin, decreased gradually from glandular ducts with only gastric mucous cell phenotype (G type) to GI-IM toward I-IM, while that of the intestinal endocrine cell markers, glicentin, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) was inversely correlated. In the fundic region, gastrin-positive cells emerged in the pseudo-pyloric and GI-IM glands, whereas I-IM glands did not possess any gastrin-positive cells, suggesting the presence of a distinct pathway of intestinalization. Double staining revealed coexistence of gastrin- and GLP-1-positive cells in the same gland and occasionally in the same cell in GI-IM glands. These results suggest that the phenotypes of endocrine cells are in line with those for mucous counterparts and support the concept that all of the different types of mucous and endocrine cells in normal and IM glands might be derived from a single progenitor cell in each gland.     

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.     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.