Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Esophageal Neoplasms/pathology* ; Epithelium/pathology* ; Metaplasia/metabolism* ; Carcinoma/pathology*

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.
Male ; Female ; Humans ; Carcinoma, Mucoepidermoid/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Biomarkers, Tumor/analysis* ; Salivary Gland Neoplasms/diagnosis* ; Transcription Factors/metabolism* ; Cystadenoma ; Metaplasia

OBJECTIVE: To assess the application of probe-based confocal laser endomicroscopy (pCLE) in diagnosis of gastric carcinoma and precancerous lesions. METHODS: Patients underwent pCLE in the First Affiliated Hospital of Zhejiang University School of Medicine during December 2013 and November 2014 and in the First Affiliated Hospital of Zhejiang Chinese Medical University during January 2014 and December 2017 were enrolled. The consistency between pCLE diagnosis and pathological diagnosis of gastric lesions, including atrophic gastritis, gastric intestinal metaplasia, low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia (including gastric carcinoma) was analyzed. RESULTS: Totally 154 gastric lesions from 119 patients were detected by pCLE. Using pathological diagnosis as gold standard, the sensitivity, specificity, coincidence rate and κ value of pCLE diagnosis for atrophic gastritis were 94.34%, 91.09%, 92.21%and 0.83; those indicators for gastric intestinal metaplasia were 84.47%, 92.16%, 87.01% and 0.72. The coincidence rate and κ value of pCLE diagnosis of complete gastric intestinal metaplasia were 0.75 and 0.49; for incomplete gastric intestinal metaplasia were 0.79 and 0.48, respectively. The sensitivity, specificity, coincidence rate and κ value of pCLE diagnosis for low-grade intraepithelial neoplasia were 85.29%, 87.50%, 87.01%and 0.66; those for high-grade intraepithelial neoplasia (including gastric carcinoma) were 95.83%, 97.17%, 96.75%and 0.92. CONCLUSIONS pCLE can be used for diagnosis of gastric carcinoma and pericancerous lesions and also for typing of gastric intestinal metaplasia.
Carcinoma ; diagnostic imaging ; Endoscopy, Gastrointestinal ; Humans ; Metaplasia ; Microscopy, Confocal ; Precancerous Conditions ; diagnostic imaging ; Sensitivity and Specificity ; Stomach ; diagnostic imaging ; pathology ; Stomach Neoplasms ; diagnostic imaging

Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Histologically, squamous metaplasia has been reported in PA, but has rarely been documented as being extensive enough to cause significant misdiagnosis. Here, we present an unusual case of PA in a 50-year-old female patient presenting with swelling on the postero-lateral aspect of the palate for a week. Histopathologically, the tumor exhibited the features of conventional PA with extensive squamous metaplasia and giant keratotic lamellae in cyst-like areas. Such exuberant squamous metaplasia and keratin can be a diagnostic and prognostic pitfall and lead to overtreatment of the patient.
Adenoma, Pleomorphic ; Diagnostic Errors ; Female ; Humans ; Medical Overuse ; Metaplasia ; Middle Aged ; Palate ; Pathology ; Salivary Glands

BACKGROUND/AIMS: To evaluate a new monoclonal antibody for Helicobacter pylori urease in gastric tissue. METHODS: A total of 107 volunteers were enrolled. All subjects underwent a 13C-urea breath test and esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia. Six biopsy specimens in the gastric antrum and body were obtained for a rapid urease test and histology. The new monoclonal antibody-based H. pylori urease test (HPU) was performed to rapidly and qualitatively detect urease in two biopsy specimens. RESULTS: H. pylori infection was diagnosed in 73 subjects. The sensitivity and specificity of the HPU was 89% and 74%, respectively. The subjects were divided into two groups: one with true-positive and true-negative HPU results (n = 90) and the other with false-positive and false-negative HPU results (n = 17). Across all subjects, ammonia levels were 900.5 +/- 646.7 and 604.3 +/- 594.3 mumol/L (p > 0.05), and pH was 3.37 +/- 1.64 and 2.82 +/- 1.51 (p > 0.05). Sensitivity was higher in the presence of atrophic gastritis or intestinal metaplasia. CONCLUSIONS: HPU detected H. pylori in approximately 10 min. Gastric aspirate ammonia and pH levels did not affect the test results. Sensitivity was good in the presence of atrophic gastritis or intestinal metaplasia.
Adult ; Antibodies, Monoclonal/*immunology ; Bacterial Proteins/*analysis/immunology ; Biomarkers/analysis ; Biopsy ; False Negative Reactions ; False Positive Reactions ; Female ; Gastritis, Atrophic/*diagnosis/microbiology ; Helicobacter Infections/*diagnosis/microbiology ; Helicobacter pylori/*enzymology/immunology ; Humans ; *Immunologic Tests ; Male ; Metaplasia ; Middle Aged ; Predictive Value of Tests ; Pyloric Antrum/*microbiology/pathology ; Reproducibility of Results ; Time Factors ; Urease/*analysis/immunology ; Workflow

OBJECTIVETo compare the difference of mucosal damage in the remnant esophagus with similar postoperative reflux after esophagectomy and gastric interposition between Chinese and Canadian population.

METHODSA prospective 1 to 1 paired study based on the same surgical approach was performed in Medical Centre of University of Montreal and West China Hospital of Sichuan University during the period from September 2010 to October 2013. The patients were followed up and evaluated by reflux symptom scoring, endoscopic assessment of mucosal damage, pathologic examination of biopsies and proliferation index test of esophageal epithelium.

RESULTSEighteen Han Chinese and 18 Caucasian Canadian patients with esophagectomy and gastric interposition were included in this study, with a follow-up period of 45 (28-67) months. There were no significant differences between the two groups in the incidence of postoperative reflux symptom, reflux symptom scoring, histological reflux esophagitis, erosion or stricture of remnant esophagus (all P>0.05). However, the incidence of mucosal metaplasia [44.4% (8/18) versus 11.1% (2/18), P=0.026], quantitative MUSE scoring [1.5 (1.0-2.0) versus 1.0 (0-2.0), P=0.042] and proliferation index [0.40 (0.30-0.45) versus 0.35 (0.30-0.50), P=0.038] of esophageal epithelium were significantly higher in Canadian patients than those in Chinese patients.

CONCLUSIONUnder similar reflux situation, esophageal mucosa of Canadian population is more sensitive to the gastroesophageal reflux damage compared with Chinese population, resulting in more severe reflux damage of remnant esophagus in Canadian patients.

Biopsy ; Canada ; China ; Esophagectomy ; adverse effects ; Gastroesophageal Reflux ; pathology ; Humans ; Metaplasia ; Mucous Membrane ; pathology ; Prospective Studies

BACKGROUND/AIMS: It is difficult to precisely detect the lateral margin during endoscopic submucosal dissection (ESD) for signet ring cell carcinoma (SRC) because SRC often expands to lateral direction through the lamina propria. Thus, the aim of this study was to classify the intramucosal spreading patterns of SRC and to analyze the patients' clinicopathological findings according to the spreading patterns. METHODS: The intramucosal spreading patterns of SRC were classified as expansive or infiltrative types. A total of 100 surgical and 42 ESD specimens were reviewed. RESULTS: In the surgical specimens, the proportions of expansive and infiltrative types were 44% and 56%, respectively. The infiltrative type was more commonly associated with old age, atrophy, and intestinal metaplasia in surrounding mucosa and the absence of Helicobacter pylori compared with the expansive type. In ESD specimens, the proportions of expansive and infiltrative types were each 50%. When lateral margin-positive lesions were compared with -negative lesions, larger size, residual lesion, and the lack of a neutrophil infiltration were more significantly associated with lateral margin-positive lesions. All cases with residual tumors in lateral margin-positive lesions were classified as the infiltrative type. CONCLUSIONS: SRC surrounded with atrophy and/or intestinal metaplasia often spreads subepithelially in the margin. This finding may suggest that a larger safety margin is necessary in this type during ESD.
Adult ; Carcinoma, Signet Ring Cell/*pathology/*surgery ; Dissection/*methods ; Female ; Gastric Mucosa/pathology ; *Gastroscopy ; Humans ; Intestines/pathology ; Male ; Metaplasia/pathology ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Stomach/pathology ; Stomach Neoplasms/*pathology/*surgery

PURPOSE: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. MATERIALS AND METHODS: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. RESULTS: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). CONCLUSIONS: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.
Atrophy ; Diagnosis ; Hedgehogs ; Helicobacter pylori* ; Helicobacter* ; Humans ; Metaplasia ; Pathology ; Recurrence* ; Stomach Neoplasms*

Renal dysplasia is a developmental disorder of the renal parenchyma involving anomalous differentiation. It is characterized by persistent metanephric ducts surrounded by primitive mesenchyme, fetal or immature glomeruli, fetal or immature tubules, interstitial fibrosis, and dysontogenic metaplasia involving tissues such as cartilage. Renal dysplasia has been rarely reported in rats. Here, we observed a small left kidney in a rat used in a short-term repeat toxicity study. The rat showed no clinical signs throughout the study. All parameters, including those reflecting kidney functions, were normal upon hematological examination and urinalysis. Grossly, the kidney was small (5 x 8 mm) and its surface appeared normal. Histological examination revealed that the cortex and medulla were poorly demarcated and contained immature/atrophic glomeruli, immature renal tubules, and mesenchymal cells. The cortex contained immature glomeruli, atrophic glomeruli with cystic dilatation of Bowman's capsular space, and some atypical tubules. Primitive metanephric tubules in the medulla were larger in diameter than normal collecting ducts, lined by a tall columnar epithelium with pale cytoplasm and basal nucleus, and surrounded by loose mesenchymal cells. Occasional tubules contained pale eosinophilic homogenous material in the lumen. Thus, this was diagnosed as a case of renal dysplasia on the basis of histologic features and is the first reported case of renal dysplasia in Sprague Dawley rats.
Animals ; Cartilage ; Cytoplasm ; Dilatation ; Eosinophils ; Epithelium ; Fibrosis ; Kidney ; Mesoderm ; Metaplasia ; Pathology ; Rats* ; Rats, Sprague-Dawley ; Urinalysis

OBJECTIVETo establish an animal model of gastric cancer by long-term infection of Helicobacter pylori (H.pylori) and to elucidate the pathogenesis by proteomics analysis.

METHODSFifty male Mongolian gerbils (4-5 week-old and weighted 60-100 g) were infected with H.pylori and the gastric tissues were obtained after the infection at 3, 6, 12 and 24 months. Histological changes were evaluated by H-E staining of the gastric tissue sections. Detection of H.pylori was performed by in-vitro culture of fresh gastric tissue samples, PCR amplification of H.pylori 16s rRNA and localization by silver staining. In addition, proteins extracted from gastric tissue samples were subjected to two-dimensional electrophoresis (2-DE) at various infection time points. Protein spots with increased quantity over the course of H.pylori infection were selected and analyzed by LC-MS/MS. Finally, differentially expressed proteins between human gastric cancer tissue samples and lymph nodes were analyzed by real-time RT-PCR.

RESULTSColonization of H.pylori was observed in gastric tissue of gerbils as early as 3 months after H.pylori infection, and persisted till 24 months. Pathological examination of infected animals showed various histological changes including acute gastritis, atrophic gastritis, intestinal metaplasia and gastric carcinoma. Seventy-eight differentially expressed proteins were identified by proteomics analysis, among which 36 proteins were up-regulated and 42 were down-regulated. Analyzed by LC-MS/MS, ten proteins were identified, including lactate dehydrogenase, ATP synthase, fatty acid-binding protein, COX5B, peroxiredoxin-4, peroxide reductase, transgelin, succinyl-CoA ligase, keratin and protein disulfide-isomerase A2, among which transgelin, ATP synthase and lactate dehydrogenase were highly expressed in human gastric carcinoma and lymph nodes.

CONCLUSIONSH.pylori infection induces the expression of transgelin, ATP synthase and lactate dehydrogenase, implying possible roles in the pathogenesis of gastric diseases including cancer.

Animals ; Disease Models, Animal ; Gastritis ; microbiology ; pathology ; Gerbillinae ; Helicobacter Infections ; complications ; metabolism ; Helicobacter pylori ; genetics ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Male ; Metaplasia ; Microfilament Proteins ; metabolism ; Muscle Proteins ; metabolism ; Proteomics ; Proton-Translocating ATPases ; metabolism ; RNA, Ribosomal, 16S ; analysis ; Stomach Neoplasms ; metabolism ; microbiology ; Tandem Mass Spectrometry