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Gastritis-associated adenocarcinoma and intestinal metaplasia in a Syrian hamster naturally infected with Helicobacter species.

The objective of this study was to evaluate stomachs of 2-year-old Syrian hamsters that were naturally colonized by multiple Helicobacter species including Helicobacter aurati. A previous report on 7- to 12-month-old Syrian hamsters described chronic gastritis and intestinal metaplasia, a putative preneoplastic lesion in the stomach, without cancer. This report describes an invasive adenocarcinoma at the pyloric-duodenal junction in one of nine hamsters at a site of helicobacter-associated inflammation and marked intestinal metaplasia. Ceca of nine of nine animals were culture positive and polymerase chain reaction positive for Helicobacter spp. Furthermore, immunohistochemical analysis of the stomach using a H. pylori polyclonal antibody detected positive-staining bacteria within the pyloric region of three of nine hamsters including the neoplastic glands. However, argyrophilic bacteria were demonstrated only within the stomach of the hamster with gastric adenocarcinoma. This is a first report of gastric adenocarcinoma in helicobacter-infected hamsters. Syrian hamsters appear suitable as potential model for studying development of helicobacter-associated gastric adenocarcinomas.

Adenocarcinoma↗

Combined sellar fibrosarcoma and prolactinoma with neuronal metaplasia: report of a case unassociated with radiotherapy.

We report the occurrence of a primary pituitary fibrosarcoma causally unrelated to radiotherapy, admixed in association with a prolactin cell pituitary adenoma showing neuronal metaplasia. These unique findings were associated with multiple endocrine neoplasia type 1 (MEN 1). Primary fibrosarcoma involving the sella is a very rare tumor. The majority of cases have been associated with prior irradiation of either a pituitary adenoma or a craniopharyngioma. Pituitary adenoma with neuronal metaplasia is also rare and usually occurs in the setting of acromegaly. Despite the intimate association of both elements in our lesion, no transition of adenoma to sarcoma was demonstrable by immunohistochemistry or in situ hybridization studies.

Adult↗

[Endocervical tubal metaplasia: morphological concepts and practical importance].

OBJECTIVE: Among uterine cervix tumor-like lesions, tubal metaplasia (TM) has been confused with endocervical in situ adenocarcinoma. TM is a benign lesion composed of three cellular types: ciliary, secretory and intercalary (or peg cell). Thus, the main purpose of this work is to localize and characterize tubal metaplasia and its relation to other morphological lesions in the cervix. METHODS: Eighteen cervical specimens from 8 cones and 10 hysterectomies with TM were reviewed in order to observe its relative frequency in different segments such as: superior, inferior, surface epithelium and glands. All cases were associated to other neoplastic and non-neoplastic diagnosis. RESULTS: TM was observed in cases with an age span from 24 to 72 years old, with a mean age of 44 years. In most of the cases (83%), TM was found in the superior region of the cervix, but in 61% TM was also found in the inferior region, either on the surface epithelium or in the glands. In 60% of the cases TM was associated with invasive or intra-epithelial neoplasia. CONCLUSIONS: In spite of being observed in the higher parts of the endocervix, TM was also detected in the lower segment, where the differential diagnosis with in situ adenocarcinoma is important. Thus, although more frequently associated with neoplasia in this study, it is not possible to determine the real incidence of TM in the cervix. However, morphological characterization of the lesion is very important for diagnostic purposes.

Adult↗

A case of breast carcinoma with cartilaginous and osseous metaplasia.

We report a case of a 49-year-old Japanese woman diagnosed with breast carcinoma with osseous and cartilaginous metaplasia with a poor outcome. Histological examination revealed invasive ductal carcinoma with undifferentiated sarcomatous components including chondrosarcomatous areas. Osseous metaplasia was also noted in a very limited area. Neither axillary lymph node metastases nor vessel invasion were observed. Immunohistochemical examination was negative for estrogen receptor, progesterone receptor and HER2 overexpression. Stage II A T2N0M0 carcinoma was diagnosed postoperatively. Five months after the operation, she developed lung metastases. Although she received systemic chemotherapy, the lesions increased in number and grew rapidly. She died of pulmonary distress 5 months after relapse.

Antineoplastic Combined Chemotherapy Protocols↗

Intestinal metaplasia, not atrophy or achlorhydria, creates a hostile environment for Helicobacter pylori.

A 54-year-old man with dyspepsia, Helicobacter pylori-associated chronic active atrophic gastritis without intestinal metaplasia, and hyperplastic gastric polyps was followed up for 1 year after H. pylori eradication with sequential endoscopic gastric mucosal mapping and gastric function tests. Eradication of H. pylori by triple therapy resulted in the histologic resolution of gastritis. However, the patient's condition, gastric function, and morphology of the polyps were not affected. This case illustrates that: a) in the absence of intestinal metaplasia, H. pylori can infect the stomach with gastric atrophy; b) the absence of acid does not preclude H. pylori infection; c) advanced atrophic gastritis may be an irreversible condition; and (d) the neutrophilic infiltrate in hyperplastic polyps is independent of the presence of H. pylori.

Achlorhydria↗

Expression of the epidermal growth factor receptor gene in human intestinal metaplasia: a preliminary report.

BACKGROUND: The role of growth factors/receptors in the etiopathology and/or development of gastric cancer has recently come under scrutiny, since overexpression or amplification of the EGF system has been found in many intestinal type gastric cancers and related to a more aggressive behavior. Since these gastric carcinomas appear to develop from intestinal metaplasia, a study was planned to investigate whether overexpression of the EGF-receptor gene also occurred in intestinal metaplastic mucosa. METHODS: Patients underwent upper GL endoscopy. Gastric biopsies for routine histology, Helicobacter pylori detection, quantification of intestinal metaplasia and EGF-R expression analysis were performed. A 30mer EGF-R specific oligonucleotide was end-labeled and used to probe a dot blot filter containing the RNA from the bioptic samples. RESULTS: Though all the gastric samples transcribed the EGF-R gene to a detectable level, overexpression of the EGF-R gene was found in the metaplastic mucosa in a minority of patients. CONCLUSIONS: These preliminary findings suggest that overexpression of the EGF-R gene is infrequent in the metaplastic gastric mucosa.

Aged↗

Histologic characterization of mouse bronchiolar cell hyperplasia, metaplasia, and neoplasia induced intratracheally by 3-methylcholanthrene.

Female B6C3F1 mice were treated intratracheally with 3-methylcholanthrene (MCA) at intervals of once every 2 weeks for a total of six doses each of 222 micrograms or 457 micrograms/mouse per dose. Animals were necropsied when found dead, moribund, or at the end of the study 43 weeks after the first treatment. Controls were treated with the vehicle (0.2% gelatin saline) only. Lungs were fixed in neutral buffered formalin and processed for light microscopic evaluation. Proliferative and metaplastic bronchiolar cell alterations were seen both within bronchioles and in the alveolar parenchyma. In both locations, changes included hyperplasia of nonciliated cells, squamous cell metaplasia, presence of ciliated cells, and mucous cell metaplasia. Mucous cells were either positive for alcian blue or the periodic-acid Schiff's reaction (PAS), or appeared eosinophilic with hematoxylin and eosin (H&E) but colorless with PAS. Tumors seemed to develop from both extra- and intrabronchiolar areas of cellular proliferation and invaded pulmonary structures. The majority were squamous cell carcinomas and adenosquamous carcinomas, accompanied by a few mucinous cell tumors and some rare tumors that were largely composed of ciliated cells. Combinations of the different metaplastic changes were frequently present in these neoplasms. In summary, it appears that tumors originating from bronchiolar cells in mice show the same morphologic variability that is observed in hyperplastic and metaplastic bronchiolar cells within airways.

Adenocarcinoma, Bronchiolo-Alveolar↗

True synovial metaplasia of breast implant capsules: a light and electron microscopic study.

The formation of true synovial-lined membranes at tissue sites not intimately related to an articulation or a tendon sheath has been described in a variety of pathologic and postsurgical conditions, but until recently has not been well recognized to occur in association with tissue surrounding silicone breast implants. Of 15 cases with resected periprosthetic breast capsules, 7 (47%) demonstrated true synovial metaplasia with capsule-implant interfaces lined by typical synovial cells. Histochemical and immunohistochemical staining reactions were essentially identical to those observed in synovial control cases and featured positive reactions to Alcian blue-periodic acid-Schiff, reticulin, and vimentin. Focal positive immunoreactivity was observed with alpha 1-antitrypsin, alpha 1-antichromotrypsin, lysozyme, and CD68. No immunoreactivity was observed with cytokeratin AE1/AE3, S-100 protein, carcinoembryonic antigen, or basement membrane antigens. Transmission electron microscopy of the lining cells confirmed their true synovial nature with the type A (macrophage-like) cells, type B (fibroblast-like) cells, and intermediate forms or type AB cells identified. We conclude that the cellular lining surrounding silicone breast implants is a true synovial membrane, that synovial metaplasia may occur in nearly one half of all resected periprosthetic capsules, and that awareness of this entity will enable the surgical pathologist to render an accurate histopathologic diagnosis.

Adult↗

Nephrogenic metaplasia of the ureter.

A case of nephrogenic metaplasia of the left ureter occurring in a 7-year-old male child, associated with recurrent urinary infection and previous surgical intervention, is described. This is to our knowledge the third reported case of this entity. Nephrogenic metaplasia involves the transitional epithelium of the urinary tract and results in the formation of structures histologically similar to renal tubules.

Child↗

Influence of various proton pump inhibitors on intestinal metaplasia in noneradicated Helicobacter pylori patients.

AIM: Intestinal metaplasia (IM) is more often found in patients with Helicobacter pylori (H pylori) infection, while eradication of H pylori results in significant reduction in the severity and activity of chronic gastritis. We aimed to determine in patients with unsuccessful eradication of H pylori the role of various proton pump inhibitors (PPIs) having different mechanisms in the resolution of IM. METHODS: We confirmed endoscopically and pathohistologically (Sydney classification) the IM in 335 patients with gastritis before and after medication for eradication of H pylori (Maastricht Protocol 2002). H pylori infection was determined by using histology, urease test and culture. Control endoscopy and histology were done after 30 d and thereafter (within 1 year). Unsuccessful eradication was considered if only one of the three tests (histology, urease and culture) was negative after therapy protocol. We used omeprazole, pantoprazole, lansoprazole in therapy protocols (in combination with two antibiotics). RESULTS: We found no significant difference in resolution of IM by using different PPI between the groups of eradicated and noneradicated patients (P<0.4821 and P<0.4388, respectively). CONCLUSION: There is no significant difference in resolution of intestinal metaplasia by different proton pump inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Distinction between short-segment Barrett's esophageal and cardiac intestinal metaplasia.

AIM: To investigate the roles of mucin histochemistry, cytokeratin 7/20 (CK7/20) immunoreactivity, clinical characteristics and endoscopy to distinguish short-segment Barrett's esophageal (SSBE) from cardiac intestinal metaplasia (CIM). METHODS: High iron diamine/Alcian blue (HID/AB) mucin-histochemical staining and immunohistochemical staining were used to classify intestinal metaplasia (IM) and to determine CK7/20 immunoreactivity pattern in SSBE and CIM, respectively, and these results were compared with endoscopical diagnosis and the positive rate of gastroesophageal reflux disease (GERD) symptoms and H pylori infection. Long-segment Barrett's esophageal and IM of gastric antrum were designed as control. RESULTS: The prevalence of type III IM was significantly higher in SSBE than in CIM (63.33% vs 23.08%, P< 0.005). The CK7/20 immunoreactivity in SSBE showed mainly Barrett's pattern (76.66%), and the GERD symptoms in most cases which showed Barrett's pattern were positive, whereas H pylori infection was negative. However, the CK7/20 immunoreactivity in CIM was gastric pattern preponderantly (61.54%), but there were 23.08% cases that showed Barrett's pattern. H pylori infection in all cases which showed gastric pattern was significantly higher than those which showed Barrett's pattern (63.83% vs 19.30%, P< 0.005), whereas the GERD symptoms in gastric pattern were significantly lower than that in Barrett's pattern (21.28% vs 85.96%, P< 0.005). CONCLUSION: Distinction of SSBE from CIM should not be based on a single method; however, the combination of clinical characteristics, histology, mucin histochemistry, CK7/20 immunoreactivity, and endoscopic biopsy should be applied. Type III IM, presence of GERD symptoms, and Barrett's CK7/20 immunoreactivity pattern may support the diagnosis of SSBE, whereas non-type III IM, positive H pylori infection, and gastric CK7/20 immunoreactivity pattern may imply CIM.

Barrett Esophagus↗

Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia.

A 58-year-old female with a recurrent history of upper abdominal pain and intermittent dysphagia underwent endoscopic evaluation that demonstrated an irregular and nodular esophago-gastric (EG) junction and grade I erosive esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett's type without dysplasia, chronic inflammation and multiple aggregates of large cells within the mucosal lamina propria, some with spindle shaped nuclei. Immunohistochemistry stains for keratins AE-1/AE-3 were negative, while S-100 and NSE were positive. This, together with routine stains, was diagnostic for mucosal ganglioneuromatosis. The background of chronic inflammation with intestinal type metaplasia was consistent with long-term reflux esophagitis. No evidence of achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable, without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic syndromes were identified in the patient including familial adenomatous polyposis and multiple endocrine neoplasia type IIb (MEN IIb). Iansoprazole (Prevacid) was started by oral administration each day with partial relief of symptoms. Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG junction. Esophageal manometry revealed a mild non-specific lower esophageal motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux disease (GERD) and we feel that the demonstration of localized ganglioneuromatosis was not likely related etiologically. In the absence of findings that might suggest neural hypertrophy, such as achalasia, the nodular mucosal irregularity seen with this instance of ganglioneuromatosis may, however, have exacerbated the patient's reflux.

Endoscopy, Gastrointestinal↗

p73 is highly expressed in myoepithelial cells and in carcinomas with metaplasia.

p73, a homologue of p53 gene, is expressed in several normal tissues including central nervous system, but data regarding tumors are scant. In this study, we have analyzed the status and expression of the p73 gene in primary breast tumors, as well as 4 normal salivary glands, 2 carcinomas with metaplasia and mixed tumors. We found that periductal myoepithelial cells of all of the mammary gland examined were clearly stained with the specific anti-p73 antibody. Furthermore, we found the expression of p73 in the neoplastic myoepithelial cells in carcinomas with metaplasia and in mixed tumors. The findings in the present study provide valuable information on the characteristics of myoepithelial cells.

Breast↗

CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications.

CDX2, a transcriptional factor expressed in the intestine, is implicated in the development and maintenance of the intestinal mucosa. Recent studies have demonstrated that CDX2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer, while it is not expressed in the normal gastric mucosa. To investigate the role of CDX2 in gastric cancer, we determined CDX2 expression and cell proliferation rate in various types of gastric cancer tissues by immunostaining. Surgically dissected gastric cancer tissues were collected from 40 patients. Consistent with previous reports, CDX2 was expressed in most gastric mucosa samples with intestinal metaplasia (89%, 16/18), although it was not found in the adjacent normal mucosa. CDX2 expression was also detected in 64% (18/28) of intestinal-type gastric cancer cases, whereas it was not observed in the diffuse-type gastric cancer (0/12). Moreover, the CDX2-positive gastric cancer samples showed significantly lower index for Ki-67 immunostaining, indicating reduced cell proliferation rates than in the CDX2-negative samples. Importantly, multivariate analysis for the overall survival rate revealed that the CDX2-positive gastric cancer patients survived significantly longer than the CDX2-negative patients. Even among the intestinal-type gastric cancer cases, the CDX2-positive group showed a lower Ki-67 index and longer postoperative survival than the CDX2-negative group. These results collectively indicate that CDX2 expression in gastric cancer tissues can be a novel prognostic marker for patient survival.

Aged↗

Effects of azoxymethane on X-ray induced intestinal metaplasia in Donryu rats.

The present study was undertaken to determine the effect of azoxymethane (AOM) administration on intestinal metaplasia induced by X-irradiation in male Donryu rats. Five-week-old animals were X-irradiated with two doses of 10 Gy each at a 3-day interval or three X-ray doses of 10 Gy at a 2-day interval and then received AOM injections i.m. at a dose of 15 mg/kg body weight once weekly for 3 weeks, 6 months after irradiation. Alkaline phosphatase positive foci were decreased after AOM treatments, but aberrant crypt like-foci appeared within areas of intestinal metaplasia. In contrast no induction was observed in normal-appearing gastric mucosa.

Alkaline Phosphatase↗

[Immunohistological investigation of squamous metaplasia and expression of cytokeratin subclasses in laryngeal epithelia].

The expression of cytokeratin (CK) subclasses was immunohistologically investigated in normal laryngeal epithelia by the ABC technique using monospecific monoclonal antibodies. There are two types of epithelium in the larynx; squamous epithelium of the glottis and ciliated epithelium mainly of the supraglottis. A difference in expression pattern was observed between these two epithelia only in 3 CKs, specifically CK-8, CK-13 and CK-19. In the glottis, CK-8 was negative in all layers, CK-13 was positive in the suprabasal and superficial layers, and CK-19 was strongly positive in the basal layer, but apparently reduced in suprabasal layers and completely negative in the superficial layers. In the supraglottis, on the contrary, CK-8 was positive except in the basal layer, CK-13 was negative in all layers, and CK-19 was positive in all layers. When ciliated epithelia were reduced to squamous metaplasia, the epithelial cells were morphologically similar to the squamous cells, and the CK expression also showed the same pattern. In proximity to this squamous metaplasia, however, there were lesions whose cell type morphologically still resembled that of the ciliated epithelium, but whose pattern of CK expression had already been reduced to that of the squamous cell.

Carcinoma, Squamous Cell↗

IFN-gamma, but not Fas, mediates reduction of allergen-induced mucous cell metaplasia by inducing apoptosis.

Inflammatory responses induced by allergen exposure cause mucous cell metaplasia (MCM) by differentiation of existing and proliferating epithelial cells into mucus-storing cells. Airway epithelia have various mechanisms that resolve these changes to form normal airway epithelia. In this report, we first investigated the state of mucous cell metaplasia and the mechanisms by which MCM is reduced despite continued exposures to allergen. After 5 days of allergen exposure, extensive MCM had developed but was reduced when allergen challenge was continued for 15 days. During this exposure period, IL-13 levels decreased and IFN-gamma levels increased in the bronchoalveolar lavage fluid. In contrast, IL-13 levels decreased but IFN-gamma was not detected at any time point during the resolution of MCM following cessation of allergen exposure. Instillation of IFN-gamma but not anti-Fas caused accelerated resolution of MCM and MCM was not resolved in Stat1-deficient mice exposed to allergen for 15 days, confirming that IFN-gamma is crucial for reducing MCM during prolonged exposures to allergen. IFN-gamma but not anti-Fas induced apoptotic cell death in proliferating normal human bronchial epithelial cells and in human bronchial epithelial cells from subjects with asthma. The apoptotic effect of IFN-gamma was caspase dependent and was inhibited by IL-13, indicating that the Th2 milieu in asthmatics may maintain MCM by preventing cell death in metaplastic mucous cells. These studies could be useful in the understanding of deficiencies leading to chronicity in airway changes and designing novel therapies to reverse MCM and airway obstruction in asthmatics.

Adult↗

[Corneal epithelium squamous metaplasia determination as diagnostic factor in limbal deficiency].

PURPOSE: To determine the correlation between the squamous metaplasia grade of the corneal surface and the clinical severity of the limbal deficiency in patients with this disorder. METHODS: We studied 98 eyes of patients with limbal deficiency by impression cytology. These patients were divided into four groups in relation to their clinical severity: 14 eyes had no symptoms, 34 eyes showed a mild grade of limbal deficiency, 28 eyes had a moderate grade and 22 eyes had severe limbal deficiency. Corneal cytology was performed in each patient. Cellular size, nuclear size, nuclear changes and the nuclear-cytoplasmic (N:C) ratio were defined in corneal epithelial cells, in addition to evaluation for the presence of goblet cells in the corneal epithelium. RESULTS: In patients with limbal deficiency without symptoms, we found that the cellular size was 477 (SD140) microm2 and the N:C ratio was 1:5.25 (SD1.5). In patients with mild limbal deficiency, the cellular size was 764 (SD122.6) microm2 and the N:C ratio was 1:8.2 (SD1.4). These patients did not show corneal conjunctivalization. In patients with moderate limbal deficiency the cellular size was 1,162 (SD340.2) microm2 and the N:C ratio was 1:13.2 (SD3.6). Some patients showed corneal conjunctivalization that was defined by the presence of goblet cells in the corneal epithelium. In patients with severe limbal deficiency, the cellular size was 2,036 (SD382) microm2 and the N:C ratio was 1:23.6 (SD4.0). Corneal conjunctivalization was present in all of these patients. CONCLUSIONS: There was a correlation between limbal deficiency severity and squamous metaplasia grade defined by impression cytology. Impression cytology was very useful for the diagnosis of cases of mild or subclinical limbal deficiency.

Corneal Diseases↗