Esophageal Lichen Planus: A Descriptive Multicenter Report.

GOALS: To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP). BACKGROUND: ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series. STUDY: A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States. RESULTS: Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers. CONCLUSIONS: Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.

Quantification of Mucosal Mast Cells in the Gastrointestinal Tract: A Primer for Practicing Pathologists.

CONTEXT.­: Mast cells are essential components of the immune system and play crucial pathogenetic roles in several digestive diseases, including mastocytic enterocolitis and eosinophilic gastrointestinal disorders. Pathologists have rarely been asked to evaluate the distribution and density of mast cells in gastrointestinal (GI) biopsy specimens. However, such requests are becoming more common because of an increasing awareness of the role of mast cells in functional GI disease and in both esophageal and nonesophageal eosinophilic gastrointestinal disorders. OBJECTIVE.­: To provide pathologists with tools to incorporate the assessment of mast cells in the evaluation of esophageal, gastric, and intestinal specimens by developing a systematic approach to their evaluation, counting, and reporting. DESIGN.­: This study consisted of a review of the literature followed by multiple consensus sessions to decide where to count mast cells and what a countable mast cell is. RESULTS.­: We reviewed 135 papers addressing the content of mast cells in the digestive tract, selected 21 that detailed how cells were counted (microscope lens, area of high-power fields, locations evaluated, type of cells considered as countable), and summarized their data in a table. Then, drawing from both the acceptable literature and our own extensive experience, we reached a tentative consensus on: (1) the normal numbers in the different segments of the GI tract; (2) the morphology of countable mast cells; and (3) the locations and strategies for counting them. CONCLUSIONS.­: The result is a set of suggestions for reporting mast cell counts, their distribution, and their location in a way clinicians can understand and use for management decisions.

Proximity to Swine Farming Operations as a Risk Factor for Eosinophilic Esophagitis.

We aimed to determine whether residential proximity to permitted swine facilities was associated with an increased risk of eosinophilic esophagitis (EoE) by conducting a case-control study using 2 complementary data sources: 1 from a tertiary care center (n = 401 cases and 1805 controls) and 1 from a large pathology group (n = 904 cases and 4074 controls). Addresses of the subjects and swine facilities were geocoded, and adjusted odds of EoE relative to proximity to and density of swine facilities were calculated. We observed a positive association between proximity to a permitted swine facility (<1 mile) and odds of EoE (adjusted odds ratio R, 2.56; 95% CI, 1.33-4.95) in the tertiary center data; density of farms (>10 farms/census tract) was also positively associated (adjusted odds ratio, 2.76; 95% CI, 1.30-5.84). However, this association was not observed in the pathology database. Though proximity to and density of swine operations were associated with EoE, associations were sensitive to the database used.

Incomplete Intestinal Metaplasia Is Rare in Autoimmune Gastritis.

BACKGROUND: Incomplete intestinal metaplasia (IM) is reportedly associated with higher gastric cancer (GC) risk than its complete variant. AGA Guidelines recommend including IM subtyping in routine pathology reports. This study assesses the prevalence of complete versus incomplete IM in gastric conditions with different GC risks. METHODS: IM subtyping (complete vs. incomplete) and grading (IM extension: G1: ≤30%; G2: >30%) were assessed in 386 patients with IM + ve gastric biopsy sets that included both antral and oxyntic samples. Cases were categorized as: (a) IM foci in otherwise normal mucosa (n = 59); (b) Helicobacter pylori gastritis (n = 138); (c) reactive gastropathy (141); and (d) autoimmune atrophic gastritis (AIG, n = 48). Odds ratios (OR) and their 95% CI were used in comparing the prevalence of incomplete IM and the correlation between subtype and IM extension. RESULTS: Incomplete IM was present in 37.7% of patients with H. pylori gastritis, 8.3% of those with AIG 5.0% of those with reactive gastropathy, and none of those with otherwise normal mucosa. Incomplete IM was strongly associated with more extensive (G2-IM) mucosal intestinalization (OR = 6.69; 95% CI = 2.77-9.40). CONCLUSION: Incomplete IM is significantly more prevalent in conditions (H. pylori gastritis) known to carry a higher risk of GC and is strongly associated with its extension. The low prevalence of incomplete IM in AIG (8.3%) and reactive gastropathy (5.2%) is in keeping with the low GC risk associated with these conditions.

Do General Pathologists Assess Gastric and Duodenal Eosinophilia?

CONTEXT.­: Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and infrequently detected by pathologists. OBJECTIVE.­: To determine whether histories of allergic or eosinophilic disorders and requests to rule out EoG and EoD affect pathologists' awareness of eosinophils in gastrointestinal biopsies. DESIGN.­: Thirty-one community-based pathologists were given 16 sets of biopsies from gastric and duodenal mucosa with elevated eosinophils, Helicobacter pylori gastritis, atrophic gastritis, normal stomach and duodenum, lymphocytosis, and celiac disease. Participants were assigned to 3 groups: group A did not receive histories of allergic or eosinophilic conditions; group B received similar histories plus a clue of possible allergic or eosinophilic conditions; and group C received the same histories as B and was asked to rule out EoG/EoD. A list of gastric and duodenal diagnoses and a space for comments were provided. Results were analyzed descriptively. RESULTS.­: Pathologists correctly diagnosed most noneosinophilic gastrointestinal disorders, indicating competence in gastrointestinal pathology. With respect to EoG and EoD, pathologists in group C performed significantly better that those in groups A and B. The combined odds ratio with 95% CI was 12.34 (2.87-53.04), P < .001, for A versus C and 4.02 (1.60-10.09), P < .02, for B versus C. CONCLUSIONS.­: Most pathologists neither reported gastric/duodenal eosinophilia nor diagnosed EoG/EoD, even when provided histories of eosinophilic disorders. Requests to rule out EoG/EoD resulted in only 4 of 11 participants evaluating and counting eosinophils in some cases. Simple evidence-based histopathologic criteria are needed before pathologists can be expected to consider and diagnose EGIDs.

The Occurrence of Gastritis in Microscopic Colitis and Inflammatory Bowel Disease.

Multiple studies have shown that Helicobacter pylori infection is associated with a lower prevalence of inflammatory bowel disease (IBD).1,2 Besides chronic active gastritis (CAG) resulting from gastric infection with H pylori, pathologists have noticed another form of CAG, which is unrelated to H pylori infection and seems to cluster in patients with IBD.3-5 The aim of the present study was to compare the prevalence of H pylori-negative and H pylori-positive CAG in patients with IBD, and microscopic colitis (MC).

Non-oesophageal eosinophilic gastrointestinal diseases are undersuspected clinically and underdiagnosed pathologically.

BACKGROUND: Non-oesophageal gastrointestinal eosinophilic diseases (EGID) are considered rare. However, low disease awareness among clinicians and pathologists may contribute to underdiagnosis. AIMS: To determine how frequently requests to evaluate for EGID accompany gastrointestinal biopsies and in what proportion of suspected cases pathologists address these requests, either confirming or refuting the clinical suspicion. METHODS: All cases in which biopsy requisitions included an explicit suspicion of EGID were extracted from a large clinicopathologic database and manually reviewed for accuracy. The diagnoses for these cases were then analysed to determine whether clinical suspicions were confirmed, refuted or ignored. RESULTS: Eosinophilic oesophagitis (EoE) was suspected in 12.8% of 903,516 patients with biopsies and confirmed in 14.9% of them. A suspicion of eosinophilic gastritis accompanied <0.001% of 1,438,206 gastric biopsy sets and was confirmed in 11.5% of them; eosinophilic duodenitis was suspected in 0.02% of ~675,519 patients with duodenal biopsies and confirmed in 8.0% of these; eosinophilic colitis was mentioned in <0.001% of 2,504,485 patients with colonic biopsies and confirmed in 0.1% of them. Less than 3% of endoscopists mentioned non-oesophageal EGID in the requisition, while most expressed a clinical suspicion of Barrett oesophagus, Helicobacter pylori gastritis, celiac disease and microscopic colitis (in 21.2%, 49.2%, 1% and 6.4% of the cases, respectively). CONCLUSIONS: Gastroenterologists and pathologists commonly address and diagnose EoE. In contrast, both clinical suspicion and diagnosis of non-oesophageal EGID are extremely rare. Increased clinical awareness might result in a better understanding of the epidemiology and improved diagnosis of these still elusive conditions.

Trends of Colonic Neoplasia in US Outpatient Endoscopy Centers.

BACKGROUND: A variety of studies have shown rising trends in the occurrence of colorectal cancer in younger patients as opposed to falling trends among older patients aged 55 years or more. We hypothesized that the time trends of benign colonic precursor lesions would reveal similar patterns. AIMS: The present study was designed to test this hypothesis in a large nationwide sample of the US population undergoing colonoscopy in community-based endoscopy centers. METHODS: The Inform Diagnostics database is an electronic repository of histopathologic records of patients distributed throughout the USA. A cross-sectional study analyzed the detection rates of sessile serrated adenomas (SSA), hyperplastic polyps (HP), tubular adenomas (TA), traditional serrated adenomas (TSA), or adenocarcinomas (colorectal cancer, CRC) in 2,910,174 colonoscopies done 2008-2020. RESULTS: During the 13-year time period, the rate of SSA showed a significant rise, both in patients younger and older than 55 years. HP and TA both showed a significant decline during the same time period. The trends of CRC in the older age group decreased significantly between 2008 (or its peak in 2012) and 2020. The trends of CRC in the younger age group increased significantly between 2008 and its peak in 2017. CONCLUSIONS: The age-specific time trends of benign and malignant colonic neoplasia are characterized by dissimilar temporal patterns. Such dissimilarity could suggest that besides a set of shared risk factors that affect all types of colonic neoplasia alike, there is yet another set of environmental risk factors that specifically influence malignant transformation.

Quantification of Mucosal Eosinophils for the Histopathologic Diagnosis of Eosinophilic Gastritis and Duodenitis: A Primer for Practicing Pathologists.

Eosinophilic gastrointestinal diseases, specifically eosinophilic gastritis and duodenitis, are chronic inflammatory conditions characterized by persistent gastrointestinal (GI) symptoms and elevated levels of activated eosinophils in the GI tract. Both clinical and endoscopic findings are nonspecific, no clinical or histopathologic diagnostic guidelines are published, and disease awareness is low, both among clinicians and amongst pathologists, who tend to overlook mild or moderate increases in the density of eosinophils in GI biopsy specimens. Yet, evaluating and, at times, counting eosinophils in GI biopsies may have important clinical implications: the numbers of tissue eosinophils correlate with clinical manifestations, can be used as determinants of effective management, and are used to assess the effects of treatment. A most persuasive argument for providing a count rather than a value judgment is that patients read reports, understand numbers, and use them to help to understand the course of their disease. The objective of this primer is to provide pathologists with the tools to incorporate a quantitative assessment of eosinophilia in the diagnosis of gastric and duodenal biopsy specimens and to develop a systematic approach to their evaluation, counting, and reporting. To achieve this aim, we present our general approach to the biopsy (where to count), followed by details on the characteristics of a countable eosinophil (what to count), and provide with a set of suggestions on the counting methods (how to count). We conclude with suggestions on how to report GI tissue eosinophilia in a manner that alerts clinicians and prompts pertinent management steps.

Lymphocytic gastritis and its relationships with other gastrointestinal disorders.

BACKGROUND: Lymphocytic gastritis (LyG) is a histopathologic finding of unknown clinical relevance. AIMS: To explore the clinical epidemiology of LyG and its associations with Helicobacter pylori (Hp) infection, coeliac disease (CD) and microscopic colitis (MC) METHODS: In a cross-sectional study, the demographic, clinical, and histopathologic data of patients with and without LyG were compared. Between 2008 and 2020, 1.5 million patients with endoscopic biopsies of the gastroduodenal mucosa were extracted from a database. LyG diagnoses were reviewed to collect detailed information regarding its topographic distribution within the stomach. In a large subgroup of 400 000 patients, tissue samples from the colon were also available. RESULTS: Of 1 481 336 patients, 341 had LyG with Hp and 2697 had Hp-negative LyG (with an overall prevalence of 0.21%). In patients with Hp-negative LyG, 450 (17%) had corpus-predominant LyG, 1068 antrum-predominant LyG (40%), and 1179 pangastric LyG (44%). LyG was more common in males and in subjects aged 50-70 years. There was no significant ethnic variation. Anaemia, diarrhoea, and weight loss were more common in patients with than without LyG. In 35% and 19% of patients, LyG was associated with CD and MC, respectively. All 72 patients with Hp-positive LyG and 280 of 310 patients with Hp-negative LyG with follow-up biopsies became free of LyG within a year. CONCLUSIONS: Most cases of LyG may represent a self-limited expression, frequently associated with other GI conditions, such as Hp infection, CD, and MC. In most patients, LyG is likely to resolve within a year after its initial diagnosis.

Gastric granulomas and Helicobacter pylori: An incidental relationship.

AIMS: Studies investigating the relationship between granulomatous gastritis (GG) and Helicobacter pylori infection have been largely inconclusive. This study was designed to determine whether the analysis of a very large number of patients would provide clearer answers evaluate the association between H. pylori infection and gastric granulomas. METHODS: We used a large national database of clinicopathological data to extract 1,673,086 patients who underwent esophagogastroduodenoscopy with gastric biopsies between 2008 and 2020. In a case-control study, we evaluated the occurrence of H. pylori infection in patients with and without gastric granulomas. We also explored other clinical and histopathological associations. RESULTS: H. pylori infection was present in 44 of 496 (8.9%) patients with gastric granulomas, compared to 158,949 (9.5%) in the control group (OR = 0.93, 95% CI = 0.68-1.26). Of the 129 patients with gastric granulomas, 50 had documented inflammatory bowel disease. CONCLUSIONS: The results of this study show that the prevalence of H. pylori infection in patients with gastric granulomas is essentially identical to that of controls with no evidence of granulomas or granulomatous disease. When patients with and without a plausible-known association for gastric granulomas were analyzed separately, the prevalence of H. pylori infection remained remarkably similar in GG patients and controls. Considering the very large numbers of patients with gastric biopsies analyzed in this study, we submit that there is no basis for suggesting that H. pylori is etiologically related to GG.

Collagenous gastritis: Epidemiology and clinical associations.

BACKGROUND: the rare occurrence of collagenous gastritis (CG) makes its epidemiology difficult to investigate. We designed a study to determine the demographic and clinical characteristics as well as the associations of CG with other upper gastrointestinal diseases in a large national clinicopathological database. METHODS: from the IDEA database we extracted all patients with histopathologically documented CG and, in a case-control study, we compared 168 subjects with and 1,286,165 subjects without CG using odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: the prevalence of CG was 13 per 100,000 EGDs. CG was significantly more common among female than male patients (OR: 1.69, 95% CI: 1.20-2.39) and was characterized by a bi-modal age distribution (first peak in patients aged 10-19, second peak primarily in females aged >60 years). CG patients presented with diarrhea (18%), anemia (12%), weight loss (11%), and vomiting (10%). CG was significantly associated with other lymphocytic disorders of the upper gastrointestinal tract, including celiac sprue (2.12, 1.55-2.88), duodenal intraepithelial lymphocytosis (3.71, 2.30-5.98), and lymphocytic gastritis (23.2, 10.9-49.5). CG persisted in 69% of patients who underwent multiple consecutive endoscopies. CONCLUSIONS: the epidemiologic features of collagenous gastritis reflect on different etiologies contributing to its occurrence in children and adults.

Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease.

In a previous study, we found a variety of inverse associations between the occurrence of gastroesophageal reflux disease (GERD) and the occurrence of various forms of inflammatory bowel disease (IBD), as well as microscopic colitis (MC) and its 2 subtypes of lymphocytic and collagenous colitis.1 Two recent studies suggested a 5-fold increase in the occurrence of eosinophilic esophagitis (EoE) among IBD patients.2,3 The aim of the present study was to confirm these positive associations between EoE and IBD.

The Meaning of Incidental Goblet Cells at the Gastroesophageal Junction.

BACKGROUND AND AIMS: The causes for the occurrence of goblet cells at the gastroesophageal junction (GEJ-GC) are unknown. The aim of our study was to compare the concurrent histologic changes of the stomach in (1) patients with GEJ-GC, but without Barrett's esophagus (BE) to those in (2) patients with BE and in (3) controls without GEJ-GC or BE. METHODS: We used an electronic database of histopathologic records from 1.3 million individual patients, who underwent esophago-gastro-duodenoscopy (EGD) in 2009-2018. We compared the prevalence of Helicobacter pylori-positive gastritis (HpG), gastric intestinal metaplasia (G-IM), chronic inactive gastritis (CIG), and reactive gastropathy (RG) among the 3 patient groups, using odds ratios and their 95% confidence intervals. RESULTS: Of all EGD patients, 4.0% harbored BE and 2.4% GEJ-GC. The average age of patients with GEJ-GC (60 ± 14) was significantly younger than the age of patients with BE (63 ± 12) and significantly older than the age of controls (55 ± 17). Female subjects were more common among GEJ-GC (54%) than BE (37%), but less common than among controls (63%). The 3 gastric histopathology changes associated with H. pylori were significantly more common in GEJ-GC than BE (for HpG 2.42, 2.29-2.56; for G-IM 1.82, 1.73-1.92; for CIG 1.31, 1.22-1.41). The corresponding differences between GEJ-GC and controls were less striking (for HpG 0.97, 0.93-1.01; for G-IM 1.15, 1.11-1.19; for CIG 0.90, 0.85-0.95). RG was slightly less common in GEJ-GC than BE (0.89, 0.86-0.92) and controls (0.94, 0.91-0.96). CONCLUSIONS: With respect to its demographic and histopathologic features, GEJ-GC likely represents gastric intestinal metaplasia as opposed to BE and should prompt gastric intestinal metaplasia screening and management.

Prevalence and concordant occurrence of esophageal, gastric, duodenal, and colonic eosinophilia.

Eosinophilic esophagitis, gastritis, duodenitis, and colitis are rare diseases. Few studies have been able to accumulate sufficiently large number of patients to analyze their clinical epidemiology. The aim of the present epidemiologic study was to examine the prevalence and concordant occurrence of gastrointestinal (GI) eosinophilia. Using a database of histopathologic records, a cross-sectional study among 302,061 patients undergoing bidirectional endoscopy evaluated the concordant occurrence of esophageal, gastric, duodenal, and colonic eosinophilia. The prevalence rates (PRs) of GI eosinophilia were expressed per 1,000 study subjects with their 95% Poisson confidence intervals (CIs). The concordant occurrence of various forms of GI eosinophilia was compared to their overall occurrence in the study population by calculating odds ratios (ORs) and their 95% CI. The database contained 3,008 patients with esophageal eosinophilia (PR = 9.96, 9.61-10.32), 366 patients with gastric eosinophilia (1.21, 1.09-1.34), 10 patients with duodenal eosinophilia (0.03, 0.02-0.06), and 124 patients with colonic eosinophilia (0.41, 0.34-0.49). The occurrence of esophageal eosinophilia was associated with an increased occurrence of gastric eosinophilia (OR = 3.58, 2.06-6.23), duodenal (40.22, 12.61-128.31), and colonic eosinophilia (8.12, 4.26-15.49). Similarly, we also found statistically significant associations between gastric eosinophilia and duodenal or colonic eosinophilia, and between duodenal and colonic eosinophilia. In the adult, as in the pediatric population, patients with any type of GI eosinophilia are at an increased risk for simultaneously harboring eosinophilia at multiple sites of their GI tract. With the exception of esophageal eosinophilia, however, other forms of GI eosinophilia are rarely diagnosed.

Low Prevalence of Helicobacter pylori-Positive Peptic Ulcers in Private Outpatient Endoscopy Centers in the United States.

OBJECTIVES: During the past decades, the prevalence of gastric and duodenal ulcers, as well as Helicobacter pylori infection, has markedly declined. We hypothesized that the decline in H. pylori prevalence has decreased the fraction of H. pylori-positive gastric and duodenal ulcers. The present study was designed to test this hypothesis in a large US population undergoing esophagogastro-duodenoscopy in community-based endoscopy centers. METHODS: The Inform Diagnostics database is a national electronic repository of histopathologic records of patients distributed throughout the United States. A cross-sectional study among 1,289,641 individual esophagogastro-duodenoscopy patients analyzed the prevalence of peptic ulcers stratified by age, sex, ethnicity, H. pylori status, year of diagnosis, and ulcer type. The joint influence of multiple predictor variables on the occurrence of gastric and duodenal ulcers was analyzed using multivariate logistic regression analysis. RESULTS: Between 2009 and 2018, the general prevalence of H. pylori infection fell significantly from 11% to 9%. This decline was accompanied by a similar decline in the fraction of H. pylori-positive gastric ulcers from 17% to 14% and H. pylori-positive duodenal ulcers from 25% to 21%. Nowadays, only 17% of all patients with ulcer harbor H. pylori. The fraction of H. pylori-positive ulcers was significantly greater in duodenal than in gastric ulcers and in male than in female patients with ulcer. The prevalence of H. pylori was 2.6-fold higher among Hispanics and 3.2-fold higher among East Asians compared with the general population. The H. pylori prevalence fell from 24% to 22% among Hispanics and from 21% to 15% among East Asians. In East Asians and Hispanics, the fraction of H. pylori-positive gastric ulcers was 37% and 35%, respectively. DISCUSSION: H. pylori infection continues to fall in the general population. Nowadays, even among patients with ulcer only a small minority harbors H. pylori infection.