Foveolar Type Research Articles

Adenoma, Hamartoma, or Something Else? Unique Diagnostic Challenges in Mixed Epithelial-Mesenchymal Lesions of the Gastrointestinal Tract

Abstract Introduction/Objective Mixed epithelial-mesenchymal lesions (MEMLs) are well-known in the gynecologic tract and, to a lesser extent, in the lungs and kidneys. However, the literature is mostly lacking in the GI tract. These cases pose significant diagnostic challenge when encountered upon, as there are many pitfalls and gray areas exist in characterization. Amongst other entities, hamartomas can account for a portion of these cases. Herein, we present a unique case of MEML identified in duodenum, which was reported as a hamartoma. Methods/Case Report A 59-year-old male presented with persistent upper GI bleeding requiring multiple transfusions. Initial upper GI endoscopy revealed an oozing ulcer as part of a 30 mm polyp in the second portion of duodenum opposite to ampulla. Epinephrine was injected for homeostasis. After repeat endoscopy failed to completely resect the lesion, the patient underwent exploratory laparotomy with resection of the 2nd portion of duodenum. The sections showed a submucosal proliferation of epithelial and mesenchymal elements. The epithelial component consisted of bland-appearing foveolar type mucinous glands, partly showing cystic dilation, while the mesenchymal component consisted of lymphovascular and neural structures as well as a population of small round cells that showed patchy SMA immunolabeling and low Ki67 proliferation index. The case was reported as hamartoma, however, a Brunner’s gland cyst and pericytic tumors (i.e. glomus tumor) were also considered. While the histologic features did not suggest malignancy, the patient had been followed-up closely for 6 months. Recurrence or malignant transformation was not reported. Results (if a Case Study enter NA) NA Conclusion MEMLs in the GI tract are always challenging to diagnose due to their rarity, unknown etiology and natural history, and lack of established risk factors. Furthermore, mesenchymal component is often difficult to characterize due to multiple differentiations and patchy/unrevealing immunohistochemistry. We report this unique case to enhance the awareness and recognition of MEMLS in the GI tract.

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50years) and intervals (2/5/10years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20mm in size, and the deep submucosal invasion rate was less than 30%. A mathematical simulation model revealed that screening every 5years starting at 45years of age could efficiently assist in identifying HpNGNs at an early stage.

Helicobacter Pylori and Metaplastic Changes in Chronic Cholecystitis: A Correlation Study

Abstract Introduction: Various types of metaplastic changes, such as gastric metaplasia (foveolar type or antral type) and intestinal metaplasia, are observed in chronic cholecystitis but not in normal mucosa. Helicobacter species can be detected in the bile and gallbladder tissue of patients with benign gallbladder disease. Objective: The present study aimed to observe the correlation between chronic cholecystitis and the presence of Helicobacter pylori as well as the different types of metaplastic changes in gallbladder mucosa. Materials and Methods: This descriptive, observational study was conducted at the Departments of Pathology and Surgery at a tertiary care medical college and hospital from April 2021 to March 2022, using a cross-sectional design. All confirmed cases of chronic cholecystitis, with or without cholelithiasis, were included in the study. Results: Intestinal metaplasia was the most common type of metaplastic change in the gallbladder epithelium in chronic cholecystitis in this region. PAS and Alcian Blue positivity were significantly higher in cases with metaplasia compared to those without metaplasia. H. pylori was detected in 3 cases (1.55%) of chronic cholecystitis in this study population. Conclusion: Mucin histochemistry may help identify early metaplastic changes in gallbladder epithelium. The use of a combination of methods for the detection of H. pylori in gallbladder tissue may increase the detection of positive cases.

The molecular profile of gastric intraepithelial foveolar type neoplasia based on somatic copy number alterations and multiple mutation analysis

BackgroundGastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN.MethodsThe aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis.ResultsTwo patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13–4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel.ConclusionsThe current molecular profiles of IFN may help elucidate the mechanisms of IFN development.

Endoscopic Diagnosis Strategy of Raspberry-Shaped Gastric Lesion in Helicobacter Pylori-Uninfected Patient.

We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and an irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogen+ously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HPs and PPI-Ls were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Mucinous cystic neoplasm of the pancreas in a male – A case report

Mucinous cystic neoplasms (MCNs) are rare tumours of the pancreas that occur almost exclusively in females and predominantly present in the body and tail. They are typically large, unilocular megacysts that do not communicate with the ductal system and are histologically lined by intestinal, pseudopyloric or gastric foveolar type epithelium that often form papillae, surrounded by characteristic dense ovarian type stroma. The WHO Classification of Tumours (5th edition) published in 2019 emphasised that the distinctive ovarian-type stroma is required for the diagnosis of MCN. MCNs in males are extremely rare and are often misdiagnosed preoperatively. Review of the literature confirmed only 14 reported cases in males up to 2017. We present a 51-year-old male that presented with a pancreatic mass who underwent a subtotal pancreatectomy and splenectomy. The lesion was completely excised and findings showed a 46 mm unilocular cystic lesion lined by low cuboidal to columnar epithelium with gastric foveolar type mucin. The wall of the cyst demonstrated the presence of ovarian type stroma confirming MCN. Immunohistochemistry showed positivity to ER and PR. The case demonstrates the importance of recognising that this rare entity can present in the male population as well.

The pathology of gastric and duodenal polyps: current concepts

The liberal use of upper endoscopy has led to an increased detection of gastric and duodenal polyps, which are identified in as many as 6 and 4.6% of patient examinations, respectively. Gastroduodenal polyps are a heterogeneous group of lesions that can be neoplastic or non-neoplastic (e.g. hyperplastic or heterotopical). Most polyps present characteristic topographical features, as well as endoscopic appearance and size. Evaluation of the surrounding mucosa is essential in assessing the underlying pathology (e.g. Helicobacter pylori, autoimmune gastritis or inherited polyposis syndromes). Phylogenetically, gastric and duodenal polyps can be classified according to the epithelial compartment from which they derive. Polyps that arise from the surface epithelium can either be of foveolar or intestinal type, and they can develop from either the native mucosa or the metaplastic epithelium (gastric intestinal metaplasia or duodenal foveolar metaplasia). Other polyps develop from the deeper glandular component, such as pyloric/oxyntic gland derived subtypes. In this review we focus upon epithelial polyps, with an emphasis on the most common and clinically relevant lesions, and present recently described entities.

Clinicopathological and Endoscopic Features of Raspberry-Shaped Gastric Cancer in Helicobacter pylori-Uninfected Patients

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia

Gastric intraepithelial foveolar type neoplasia (IEFN) is not well defined. In addition, atrophic mucosa (AM) is an important issue to consider when evaluating gastric tumorigenesis. Here, we assessed the clinicopathological characteristics and molecular alterations contributing to the development of IEFN compared with intestinal type neoplasia. We examined the clinicopathological and molecular features of 42 cases of IEFN with low-grade dysplasia (LGD) and those of 77 cases of intraepithelial intestinal type neoplasia (IEIN) with LGD. The clinicopathological and molecular features examined included the AM status, mucin phenotype expression, CDX2 expression, p53 overexpression, β-catenin intranuclear accumulation, microsatellite instability (MSI), DNA methylation status (low methylation epigenotype [LME], intermediate ME, or high ME), allelic imbalances (AIs), and APC promoter 1B mutations. There were no differences in the frequencies of AM and rates of CDX2 expression between IEFN and IEIN cases. Although no differences in the frequencies of p53 overexpression and MSI were observed between the two histological types, intranuclear expression of β-catenin was significantly higher in IEIN than in IEFN. In addition, although the rate of LME was significantly higher in IEFN cases than in IEIN cases, IEFN was characterized by AIs at multiple foci. Finally, mutation of the APC promoter 1B, which is a characteristic of gastric adenocarcinoma and proximal polyposis of the stomach (potentially resembling IEFN), was detected in only one IEFN case. These findings suggested that IEFN may be an independent entity in terms of molecular alterations including the presence of multiple AIs and LME.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients.

BACKGROUNDPersistent Helicobacter pylori (H. pylori) infection causes chronic inflammation, atrophy of the gastric mucosa, and a high risk of developing gastric cancer. In recent years, awareness of eradication therapy has increased in Japan. As H. pylori infections decrease, the proportion of gastric cancers arising from H. pylori uninfected gastric mucosa will increase. The emergence of gastric cancer arising in H. pylori uninfected patients though rarely reported, is a concern to be addressed and needs elucidation of its clinicopathological features.AIMTo evaluate the clinicopathological features of early gastric cancer in H. pylori-uninfected patients.METHODSA total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019. Of these, 30 lesions in 30 patients were diagnosed as H. pylori-uninfected gastric cancer (HpUIGC). We defined a patient as H. pylori-uninfected using the following three criteria: (1) The patient did not receive treatment for H. pylori, which was determined by investigating medical records and conducting patient interviews; (2) Lack of endoscopic atrophy; and (3) The patient was negative for H. pylori after being tested at least twice using various diagnostic methods, including serum anti-H. pylori-IgG antibody, urease breath test, rapid urease test, and microscopic examination.RESULTSThe frequency of HpUIGC was 1.2% (30/2462) for the patients in our study. The study included 19 males and 11 females with a mean age of 59 years. The location of the stomach lesions was divided into three sections; upper third (U), middle third (M), lower third (L). Of the 30 lesions, 15 were U, 1 was M, and 14 were L. Morphologically, 17 lesions were protruded and flat elevated type (0-I, 0-IIa, 0-IIa + IIc), and 13 lesions were flat and depressed type (0-IIb, 0-IIc). The median tumor diameter was 8 mm (range 2-98 mm). Histological analysis revealed that 22 lesions (73.3%) were differentiated type.The HpUIGC lesions were classified into fundic gland type adenocarcinoma (7 cases), foveolar type well-differentiated adenocarcinoma (8 cases), intestinal phenotype adenocarcinoma (7 cases), and pure signet-ring cell carcinoma (8 cases). Among 30 HpUIGCs, 24 lesions (80%) were limited to the mucosa; wherein, the remaining 6 lesions showed submucosal invasion. One of the submucosal invasive lesions showed more than 500 μm invasion. The mucin phenotype analysis identified 7 HpUIGC with intestinal phenotype and 23 with gastric phenotype.CONCLUSIONWe elucidated the clinicopathological characteristics of HpUIGC, revealing recognition not only undifferentiated-type but also differentiated-type. In addition, intestinal phenotype tumors were also observed and could be an important tip.

Endoscopic and Pathological Characteristics of Helicobacter pylori Infection-Negative Early Gastric Cancer

Background: The characteristics of Helicobacter pylori (HP) infection-negative gastric cancer (HPINGC) have not been well documented because of the rareness. The aim of this study was to classify HPINGC endoscopically and clinicopathologically. Methods: This retrospective study included 1,741 early gastric cancer lesions and evaluated their HP infection status. Expression levels of MUC5AC, MUC6, MUC2, CD10, p53, MIB-1, pepsinogen-I, H⁺/K⁺ ATPase, chromogranin A, E-cadherin, and gastrin were evaluated in tumors by immunohistochemistry (IHC). Results: Among the analyzed lesions, 19 (1.1%) were diagnosed as HPINGC and classified into 6 types: undifferentiated (5 lesions), fundic gland (2 lesions), cardiac gland (1 lesion), pyloric gland (3 lesions), foveolar (5 lesions), and mixed (3 lesions) types. Undifferentiated lesions were of pale color, with unclear demarcation and decreased E-cadherin expression. Fundic-type lesions were tan to reddish in color, with submucosal tumor-like protrusions, and positive for pepsinogen-I and H⁺/K⁺ ATPase. The cardiac gland type was located in the gastroesophageal junction and was positive for MUC6 and pepsinogen-I. Pyloric gland-type lesions were of the same color as normal mucosa, with mild elevation and unclear demarcation, likely positive for CD10 and chromogranin A. Foveolar epithelial-type lesions were white and elevated, with defined demarcation, and contained MUC5AC-positive cells. Mixed-type lesions, showing various staining patterns in IHC, had both elevated and depressed shape and reddish color. Conclusion: Endoscopic observation and IHC were useful for classifying the characteristics of HPINGC, which may preserve the characteristics of its region of origin.

Pyloric and foveolar type metaplasia are important diagnostic features in Crohn's disease that are frequently missed in routine pathology.

Pyloric type metaplasia (PYME) as evidence of chronic mucosal damage, is one of the main histopathological findings for diagnosing Crohn's Disease (CD) in terminal ileum biopsies, according to the latest guidelines but still frequently underdiagnosed in routine pathology. Foveolar metaplasia (FOME) changes in mucosa, another aspect of the chronic post -inflammatory Ulcer Associated Cell Lineage (UACL), have only been reported in a few cases. However, their clinical significance has not been investigated in depth except in pouchitis. The aim of this study was to investigate the importance of meticulous study of terminal ileum biopsies for the recognition of PYME/FOME as an adjunct finding helpful for the diagnosis of CD. In the present study, two experienced gastrointestinal pathologists, have reviewed 105 terminal ileum biopsies from 105 patients with CD, using a protocol of 15 sections on average per biopsy. In 21% (22/105) of cases PYME was recognized and in 4% (4/105) FOME was also present. PYME/FOME had not been detected in 83% of these cases in the original reports. FOME was also identified in terminal ileum biopsies, a feature not reported previously in CD. Conclusively, PYME/FOME can be easily missed in terminal ileum biopsies from patients with suspected or known CD unless a meticulous study of the histologic material is carried out combined with awareness of the pathologist about its importance.

Histological analysis of fundic gland polyps secondary to PPI therapy.

The aim of this study was to clarify the histopathological features of fundic gland polyps (FGPs) in patients treated with proton pump inhibitors (PPIs) and to investigate the mechanism of enlargement of FGPs after PPI treatment. A total of 196 biopsy specimens of FGPs, which consisted of 87 FGPs in patients treated with PPIs (PPI group) and 109 FGPs in patients treated without PPIs (non-PPI group) were compared histologically using haematoxylin and eosin staining, Ki67 immunohistochemistry and multiplex immunohistochemical stain with Ki67, MUC5AC and MUC6. The significant histological features of FGPs in the PPI group were: larger size of dilated fundic gland cysts, larger number of foveolar and mixture type fundic gland cysts, foveolar cell hyperplasia, parietal cell protrusion, mononuclear cell infiltration and a higher percentage of Ki67-positive cells in the deeper layers of the glands. Multiplex immunohistochemical stain showed that Ki67-positive cells were also positive for MUC5AC, and the Ki67-positive rate was significantly higher in MUC5AC-positive cells of the PPI group than of the non-PPI group. Gene mutations of β-catenin were found in only 9.7% of FGPs in the PPI group. Enlargement of fundic gland cysts due to foveolar cell proliferation and parietal cell protrusion might promote the enlargement of FGPs in patients treated with PPIs. β-catenin gene mutations might not be associated with these histological changes of FGPs after PPI treatment.

Mucin phenotype of differentiated early gastric cancer: an immunohistochemistry study supporting therapeutic decision making.

Introduction: Endoscopic submucosal dissection is widely employed in early gastric cancer (EGC). Foveolar phenotypes should be distinguished from the other differentiated EGC (DEGC) types because of their increased malignant potential. The phenotypic classification could be useful not only for investigating EGC tumorigenesis but also for evaluating the tumor aggressiveness to guide treatment decision making.Methods: On surgical tissue specimens, we studied the mucin phenotype of EGC to distinguish cases with a worse prognosis dictating different therapeutic options or a very close surveillance program. DEGC in our series were classified as mucin foveolar (51%) or mucin intestinal (49%) phenotype. We evaluated correlations among foveolar and intestinal phenotypic markers, tumor patterns, clinicopathologic features and prognostic and therapeutic implications. Immunohistochemistry (IHC) for MUC5AC and CDX2 was performed on 63 EGC patient specimens. MUCA5C was employed as gastric foveolar phenotypic marker and CDX2 as intestinal phenotypic marker.Results: Foveolar DEGC was significantly associated with larger tumor size (p=0.01), high grade (G2-G3) (p=0.001), vessel permeation (p=0.05), lymph node metastasis (p=0.001) and ulceration (p=0.001), whereas intestinal type DEGC was associated with low grade (p=0.001).Conclusion: IHC determination of the mucin phenotype is an easy, inexpensive method that can provide useful, sensitive markers distinguishing the foveolar or intestinal phenotype in DEGC. The precise identification of the foveolar type, featuring a poorer prognosis, should sound a warning bell mandating very close study of the lesion before endoscopic treatment or contraindicating endoscopic resection in favor of the open surgery option.

Gastric Heterotopia in the Rectum: Donʼt Let Looks Deceive You

Gastric heterotopia in the rectum is an extremely rare gastrointestinal entity with very few cases reported in the literature. Although it is an uncommon finding, it can lead to serious complications including rectal bleeding, rectal and abdominal pain, and most importantly, an increased risk for malignant transformation. Here we present a very rare case of an asymptomatic patient diagnosed with gastric heterotopia of the rectum after an initial screening colonoscopy. This is the case of a 51 year-old male with a medical history of gastroesophageal reflux disease that was seen at gastroenterology clinics for initial screening colonoscopy. At evaluation the patient was asymptomatic, denying weight loss, abdominal pain, diarrhea, constipation, melena, hematochezia, rectal pain, or changes in stool caliber. The patient had no pertinent family history and the only medication taken was omeprazole twice daily. On examination, vital signs were within normal limits and his physical did not reveal any abnormal findings. Laboratory tests were unremarkable. Colonoscopy was performed without complications and revealed four diminutive sessile polyps measuring < 0.5 cm at 2cm from anal verge (Figure 1). The histopathological evaluation revealed that all four were hyperplastic polyps (Figure 2). However, one small focus of pyloric glands and overlying foveolar type epithelium was identified (Figure 2-3), consistent with heterotopic gastric mucosa of the rectum. Gastric heterotopia refers to the presence of normal gastric mucosal tissue located in a non-physiological site, entirely apart from the stomach. It can occur anywhere along the gastrointestinal tract with most common sites being the esophagus and duodenum. However, the presence of gastric mucosa in the rectum is exceedingly rare with only approximately 50 cases described in the literature. Symptoms include painless rectal bleeding, rectal and abdominal pain. Rectum involvement of gastric heterotopia is usually observed endoscopically as a polyp, diverticula or ulcer. Histopathology is essential for diagnosis, with oxyntic type mucosa typically observed. Other histologic findings include mixed oxyntic, antral mucosa and pyloric type mucosa from which adenocarcinoma can arise. These lesions have an increased risk of malignancy, which warrants great awareness by physicians and close follow up. Here we observe that these lesions can present like a typical polyp, making biopsies an essential part of any colonoscopy.1494_A Figure 1. Diminutive sessile polyp at rectum.1494_B Figure 2. (A) Focus of pyloric glands with overlying foveolar type epithelium. (B) Hyperplastic polyp with superficial serrated architecture.1494_C Figure 3. Pyloric type gastric mucosa in rectum

Characterization of Helicobacter pylori-Naïve Early Gastric Cancers

Aim: Helicobacter pylori-naïve gastric cancers(GCs) have not been well documented. We aimed to characterize early H. pylori-naïve GCs. Subjects and Methods: Of 666 patients with GC resected by endoscopic submucosal dissection, H. pylori-naïve patients were extracted according to the definition: no H. pylori eradication history, negative for serum H. pylori-antibody and current H. pylori-infection tests, and no gastric atrophy by pepsinogen (PG) test, endoscopy, and histology. Results: It was found that 16 GCs were H. pylori-naïve, and classified into undifferentiated and differentiated type adenocarcinoma. All 9 undifferentiated type GCs were pale, depressed, mucosal pure signet ring cell adenocarcinoma except one of them and 7 differentiated type GCs were classified into 3 fundic gland type GCs and 4 foveolar type GCs. All fundic gland type GCs positive for PG-1 were cardia small submucosal tumor (SMT)-like protrusions with dilated vessels on the surface. All 4 foveolar type GCs were composed of dysplastic clear cells resembling foveolar epithelium, negative for PG-1 but positive for mucin 6 (MUC6) and MUC5AC. Endoscopically, all were laterally spreading elevations with papillary or villous surface. Conclusions: H. pylori-naïve GCs were infrequent at 2.5%, and classified into 3 types: a small pale depression of signet ring cell adenocarcinoma, a small SMT-like protrusion of fundic gland type GC, and a large laterally spreading elevation of foveolar type GC.

Correction: The different pathogenesis of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum.

[This corrects the article DOI: 10.18632/oncotarget.17051.].

Rare Case of Large Size Circumferential Cervical Inlet Patch

Heterotopic Gastric Mucosa (HCM) is abnormally placed gastric mucosa outside of the stomach and can be found ubiquitously within the GI tract. The most common location is in the proximal esophagus just distal to the esophageal sphincter known as a cervical inlet patch (CIP). Due to the active secretion of acid and or mucous, clinical complications from these ectopic tissues arise as esophagitis, ulcers, webs, strictures, hoarseness, sore throat, cough, heartburn, dysphagia, odynophagia and globus sensation (lump in throat) that may necessitate screening biopsies and or serial dilatations. It is extremely rare to encounter a CIP large enough to cover the entire circumference of the esophagus seen in our patient, who presented as an asymptomatic thirty-nine year old female incidentally found to have circumferential CIPs measuring 20x28mm area in total. Although uncommon, dysplastic changes and malignancies in association with CIPs have been reported. However, this was not found in our patient as biopsy demonstrated no malignant changes. Pathology describes the lesions as gastric foveolar type surface epithelium and squamous epithelium with underlying gastric cardio-fundic type glands along with focal erosions, moderate acute and chronic inflammation. Up to date, patient continues to regularly follow up in clinic and has been doing well.Figure: Endoscopic view of an inlet patch with salmon colored gastric mucosa.Figure: Low power histology the inlet patch showing gastric mucosa and normal esophageal mucosa.Figure: High power histology of the patch showing gastric type mucosa.

The different pathogeneses of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum.

Non-ampullary duodenal adenoma with activation of Wnt/β-catenin signalling is common in familial adenomatous polyposis (FAP) patients, whereas sporadic non-ampullary adenoma is uncommon. The adenoma-carcinoma sequence similar to colon cancer is associated with duodenal tumors in FAP, but not always in sporadic tumors. We obtained 37 non-ampullary duodenal tumors, including 25 adenomas and 12 adenocarcinomas, were obtained from biopsies and endoscopic resections. We performed immunohistochemistry for β-catenin, the hallmark of Wnt activation, and aldehyde dehydrogenase 1 (ALDH1), a putative cancer stem cell marker. In non-ampullary lesions, abnormal nuclear localization of β-catenin was observed in 21 (84.0%) of 25 adenomas and 4 (33.3%) of 12 adenocarcinomas. In the proximal duodenum, nuclear β-catenin was less frequent in both adenomas and adenocarcinomas. Gastric duodenal metaplasia (GDM) was observed only in the proximal duodenum. All adenomas with GDM were the gastric foveolar and pyloric gland types, and showed only membranous β-catenin. The intestinal-type adenomas had nuclear β-catenin in the proximal and distal duodenum. ALDH1-positive cells were more frequent in adenocarcinomas than adenomas. Nuclear β-catenin accumulation frequently occurred in ALDH1-positive cells in adenoma, but not in adenocarcinoma. In the non-ampullary proximal duodenum, Wnt/β-catenin pathway activation was more closely associated with adenomas than adenocarcinomas, and while it might cooperate with ALDH1 in adenoma, it does not in adenocarcinoma. The pathogenesis thus may differ between sporadic adenoma and adenocarcinoma of non-ampullary duodenal lesions, especially in the proximal and distal duodenum.

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors).

ObjectiveEpithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors.Materials and methodsAmong duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO) 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands.ResultsAs for patient characteristics, there were 76 men (75.2%) and 25 women (24.8%), with a median age of 65 years (range, 34 to 84). The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1%) and gastric-type tumors (12 lesions, 10.9%). Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7%) and tubulovillous-type tumors (7 lesions, 6.4%). Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7%) and pyloric gland-type (PG) tumors (9 lesions, 8.2%). The grade of atypia was significantly higher in gastric-type tumors (p<0.01). PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands.ConclusionsAbout 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.