Clinical significance of colonic intraepithelial lymphocytosis in a pediatric population.

The significance of colonic intraepithelial lymphocytosis has been well described in adults, and is associated with lymphocytic colitis, untreated celiac disease, and medications, among others. Little is known about the meaning of colonic intraepithelial lymphocytosis in the pediatric population; this study examines this finding in a cohort of children. Twenty patients in whom colonic intraepithelial lymphocytosis was a prominent feature were identified from 1999 to 2005. Colonic intraepithelial lymphocytosis was defined as 20 or more intraepithelial lymphocytes per 100 colonocytes present in at least one colonic mucosal biopsy. Each biopsy was examined for numbers of intraepithelial lymphocytes per 100 surface and crypt colonocytes; various architectural, inflammatory, and metaplastic changes were also noted. When available, concurrent duodenal and/or ileal biopsies were examined. Studied clinical parameters included indications for biopsy, clinical follow-up, final diagnosis, comorbidities, autoimmune serologies, and medications. A total of 121 colonic mucosal biopsies were examined in 20 patients who ranged from 1 to 17 years (mean 10.2 years; 40% male). Common indications for endoscopy included diarrhea and abdominal pain. A mean of 29 (+/-22) intraepithelial lymphocytes per 100 enterocytes were seen. Seven patients had colonic intraepithelial lymphocytosis as the only histologic finding. The remaining 13 patients had additional architectural, inflammatory, and metaplastic changes. The mean follow-up period was 14 months (range 1-48 months). Inflammatory bowel disease was diagnosed in 4 of 20 patients and was seen chiefly in biopsies in which colonic intraepithelial lymphocytosis was associated with architectural or inflammatory changes. Common disease associations include celiac disease, lymphocytic colitis, and autoimmune enteropathy. Pediatric colonic intraepithelial lymphocytosis, in the absence of other histologic findings, is associated with various diseases, including celiac disease, lymphocytic colitis, and autoimmune enteropathy. Colonic intraepithelial lymphocytosis in the presence of other inflammatory changes indicates the possibility of idiopathic inflammatory bowel disease. These findings are similar to those seen in adults, with the exception of autoimmune enteropathy.

Morphologic features are useful in distinguishing Barrett esophagus from carditis with intestinal metaplasia.

Barrett esophagus (BE) and carditis with intestinal metaplasia (CIM) differ in their risk of malignancy and implications for patient management, but are difficult to distinguish in mucosal biopsies from the gastroesophageal junction region. The present study was performed to evaluate the role of routine morphology in distinguishing BE from CIM in mucosal biopsies and to assess the degree of interobserver variability in recognizing morphologic parameters that are of significance in making this distinction. Several morphologic features, including presence of crypt disarray and atrophy, incomplete and diffuse intestinal metaplasia, multilayered epithelium, squamous epithelium overlying columnar crypts with intestinal metaplasia, hybrid glands, and esophageal glands/ducts, were significantly associated with a diagnosis of BE. The latter 3 features were observed exclusively in BE biopsies. Furthermore, multiple BE-associated morphologic features were often present together in BE but not CIM biopsies. There was substantial agreement (kappa=0.6) among expert gastrointestinal pathologists for distinguishing BE from CIM even in the absence of clinical/endoscopic information. The interobserver agreement in recognition of BE-associated morphologic features ranged from almost perfect for some features like esophageal glands/ducts (kappa=0.83) to slight for multilayered epithelium (kappa=0.17). In conclusion, our findings indicate that several morphologic features are helpful in distinguishing BE from CIM. The combined presence of multiple BE-associated morphologic features can be used in making this distinction with a high degree of accuracy. Larger prospective studies need to be performed to validate these findings and evaluate the reproducibility of this approach in routine clinical practice.

Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America.

BACKGROUND: Studies of pediatric inflammatory bowel disease (IBD) have varied in the criteria used to classify patients as having Crohn disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). Patients undergoing an initial evaluation for IBD will often undergo a series of diagnostic tests, including barium upper gastrointestinal series with small bowel follow-through, abdominal CT, upper endoscopy, and colonoscopy with biopsies. Other tests performed less frequently include magnetic resonance imaging scans, serological testing, and capsule endoscopy. The large amount of clinical information obtained may make a physician uncertain as to whether to label a patient as having CD or UC. Nevertheless, to facilitate the conduct of epidemiological studies in children, to allow the entry of children into clinical trials, and to allow physicians to more clearly discuss diagnosis with their patients, it is important that clinicians be able to differentiate between CD and UC. METHODS: A consensus conference regarding the diagnosis and classification of pediatric IBD was organized by the Crohn's and Colitis Foundation of America. The meeting included 10 pediatric gastroenterologists and 4 pediatric pathologists. The primary aim was to determine the utility of endoscopy and histology in establishing the diagnosis of CD and UC. Each member of the group was assigned a topic for review. Topics evaluated included differentiating inflammatory bowel disease from acute self-limited colitis, endoscopic and histological features that allow differentiation between CD and UC, upper endoscopic features seen in both CD and UC, ileal inflammation and "backwash ileitis" in UC, patchiness and rectal sparing in pediatric IBD, periappendiceal inflammation in CD and UC, and definitions of IC. RESULTS: Patients with UC may have histological features such as microscopic inflammation of the ileum, histological gastritis, periappendiceal inflammation, patchiness, and relative rectal sparing at the time of diagnosis. These findings should not prompt the clinician to change the diagnosis from UC to CD. Other endoscopic findings, such as macroscopic cobblestoning, segmental colitis, ileal stenosis and ulceration, perianal disease, and multiple granulomas in the small bowel or colon more strongly suggest a diagnosis of CD. An algorithm is provided to enable the clinician to differentiate more reliably between these 2 entities. CONCLUSIONS: The recommendations and algorithm presented here aim to assist the clinician in differentiating childhood UC from CD. We hope the recommendations in this report will reduce variability among practitioners in how they use the terms "ulcerative colitis," "Crohn disease," and "indeterminate colitis." The authors hope that progress being made in genetic, serological, and imaging studies leads to more reliable phenotyping.

Allergic eosinophilic esophagitis: a primer for pathologists.

Allergic eosinophilic esophagitis is a recently described clinical-pathologic entity that is being increasingly recognized in children and adults. In this review, we evaluate current information on the clinical, endoscopic, and pathologic features of this condition and summarize the most useful parameters that support its diagnosis.

Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin.

Inflammatory fibroid polyps (IFPs) are rare mesenchymal tumors of the gastrointestinal tract that consist of spindle-shaped stromal cells and an inflammatory infiltrate rich in eosinophils. Their etiology and histogenesis remain unknown. Based on previous reports of their immunoreactivity for CD34 and c-kit biomarkers, IFPs have been thought to be related to gastrointestinal stromal tumors (GISTs). After reviewing the current literature and examining IFPs at the light microscopic level, we evaluated a series of IFPs using an extensive panel of immunohistochemical and in situ hybridization markers in an effort to gain insight into their etiology and histogenesis and to determine their true relationship to GISTs. Sixteen routinely processed IFP specimens (14 gastric, 1 ileal, and 1 rectal) were immunohistochemically stained for antibodies to CD34, HMB-45, desmin, smooth muscle actin, calponin, h-caldesmon, anaplastic lymphoma kinase, S-100 protein, epithelial membrane antigen, c-kit (CD117), stem cell factor (SCF/N19 or kit ligand), p53, bcl-2, cyclin D1, and human herpesvirus-8 (HHV8). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also performed. Ten cases were further evaluated for the dendritic cell markers fascin, CD21, CD23, and CD35. Stromal cells were diffusely positive for CD34 and fascin in all (100%) cases, and these stromal cells were, in addition, immunoreactive for calponin and smooth muscle actin in 88% and 25% of cases, respectively. CD35 was also found to be focally reactive in the stromal cells. Cyclin-D1 was overexpressed in all (100%) IFPs. All other immunohistochemical markers and EBER were negative in the stromal cells. These findings suggest that the proliferating stromal cells in IFPs are of dendritic cell origin, with some cases also exhibiting myofibroblastic features. Absence of c-kit, SCF, and h-caldesmon immunoreactivity fails to support a relationship to GISTs. We also conclude that Epstein Barr virus and HHV8 are unlikely etiologic agents of IFPs. Overexpression of cyclin D1 in all cases suggests that a defect in cell-cycle regulation may be involved in the growth of IFPs.

Pathologic features of reflux and Helicobacter pylori-associated carditis: a comparative study.

Inflammation of the gastric cardia, which is the most proximal portion of the stomach, in most instances is the result of either gastroesophageal reflux disease or H. pylori infection. Histologic distinction between these two entities is important because the treatment, natural history, and risk of malignancy are different. Moreover, multilayered epithelium, a possible precursor to Barrett's esophagus, has only recently been described in the gastric cardia, and its relationship to gastroesophageal reflux disease is unknown. The aim of this study was to compare the histologic features of the gastric cardia and the prevalence of multilayered epithelium in patients with reflux versus H. pylori-associated carditis. Routinely processed hematoxylin and eosin-stained mucosal biopsies of the gastric cardia from 30 patients with reflux-associated carditis, 25 with H. pylori-associated carditis, and 30 control patients (no reflux, no H. pylori) were evaluated for a wide variety of histologic features such as goblet cell metaplasia, presence of multilayered epithelium, type of glandular epithelium (mucous, oxyntic, mixed mucous/oxyntic), pancreatic metaplasia, overall degree of inflammation, and the quantity of individual types of inflammatory cells. The clinical and histologic features were compared between the two study groups and controls. Clinically, the reflux carditis group (male/female ratio: 21/9, mean age 56 years) had a significantly higher male/female ratio (p <0.01) and a slightly higher mean age in comparison with the H. pylori group (male/female ratio: 9/16, mean age 50 years). Histologically, the reflux group had significantly less overall inflammation (p <0.05), with fewer plasma cells (p <0.04) and neutrophils (p <0.006), but a higher prevalence of multilayered epithelium [9 of 30 (30%) vs 1 of 25 (4%) in the H. pylori group, p = 0.01]. In the reflux carditis group, multilayered epithelium was significantly associated with neutrophilic inflammation (p <0.05), but not any other features of chronic carditis or with any of the specific epithelial cell types. The control group showed less inflammatory activity in comparison with the H. pylori group and a lower prevalence of multilayered epithelium and eosinophilic inflammation in comparison with the reflux group. The clinical and pathologic features of reflux carditis are distinct from H. pylori carditis and are characterized by less overall inflammation and fewer neutrophils and plasma cells. Multilayered epithelium not uncommonly occurs in the cardia of patients with gastroesophageal reflux disease but without Barrett's esophagus, further supporting our hypothesis that multilayered epithelium may represent an early precursor in the development of columnar metaplasia in Barrett's esophagus.

Utility of MMP-1, p53, E-cadherin, and collagen IV immunohistochemical stains in the differential diagnosis of adenomas with misplaced epithelium versus adenomas with invasive adenocarcinoma.

Adenomas with misplaced epithelium in the submucosa of the polyp stalk ("pseudoinvasion") may be difficult to distinguish from adenomas that harbor invasive adenocarcinoma by morphologic analysis. Recently, several epithelial and stromal proteins, such as matrix metalloproteinase-1 (MMP-1), p53, E-cadherin, and collagen IV, have been shown to be altered in colonic adenocarcinomas in comparison with adenomas and normal colonic mucosa. Therefore, the purpose of this study was to evaluate the diagnostic use of several epithelial (p53, E-cadherin) and stromal (MMP-1, collagen IV) markers in distinguishing adenomas with misplaced epithelium from those with invasive adenocarcinoma. Routinely processed polypectomy specimens from 23 patients with an adenoma with misplaced epithelium (male/female ratio 12/11; mean age 65 years) and 23 patients with an adenocarcinoma arising in an adenoma (male/female ratio 13/10; mean age 63 years) were immunohistochemically stained (avidin-biotin complex method) for monoclonal antibodies to MMP-1 (epithelial and stromal cell collagenase), p53 (tumor suppression gene), E-cadherin (intercellular adhesion protein), and collagen IV (basement membrane collagen component), and the results were compared between the two polyp groups. Where appropriate, immunopositivity was evaluated in the epithelium (MMP-1, p53, E-cadherin), stroma (MMP-1), and/or basement membrane (collagen IV). Cases were considered positive if an increase (MMP-1, p53) or decrease (E-cadherin, collagen IV) in either the intensity or proportion of cells staining was noted in the submucosal epithelial component compared with the intramucosal portion of the polyp head for each individual polyp. In adenomas with invasive adenocarcinoma, MMP-1 staining of the stroma surrounding submucosal epithelium and p53 nuclear staining within the epithelium were increased in 21 (91%) and 14 (61%) cases, respectively, whereas decreased or discontinuous E-cadherin and collagen IV staining was noted in 15 (65%) and 22 (96%) cases, respectively. All these values were significantly different (p < 0.005) from those observed in adenomas with misplaced epithelium [MMP-1, 11 of 23 (48%); p53, 1 of 23 (4%); E-cadherin, 0 of 23 (0%); collagen IV, 0/23 (0%)]. Furthermore, in three diagnostically difficult cases that contained foci of misplaced epithelium with high-grade dysplasia, the immunohistochemical results confirmed the impression that the lesions represented epithelial misplacement rather than invasive adenocarcinoma. In conclusion, the degree and/or pattern of MMP-1, p53, E-cadherin, and collagen IV staining in the submucosal epithelial elements in comparison with the intramucosal adenomatous tissue may help distinguish adenomas with misplaced epithelium from those with invasive adenocarcinoma.

Morphology of the cardia and significance of carditis in pediatric patients.

The morphology of the gastric cardia in children and the significance of inflammation in this region are unknown. Some investigators propose that the cardia is comprised of mucous glands at birth, whereas others suggest that mucous glands, when present, represent a metaplastic response to gastroesophageal reflux disease. The aim of this study was to evaluate the morphologic features of the cardia in a pediatric population and to determine the significance of inflammation in this region by correlating the pathologic features with clinical and endoscopic data. Routinely processed hematoxylin and eosin-stained mucosal biopsies of the cardia from 74 pediatric patients (age range 0.1-18 years; male/female ratio 0.76:1) without endoscopic evidence of Barrett's esophagus were examined for a variety of histologic features, such as the type of glandular epithelium (mucous, mixed mucous/oxyntic, oxyntic), and the amount and type of inflammation both within 1.0 mm and >1.0 mm from the squamocolumnar junction. The results were correlated with the patients' clinical symptoms and with other histologic features, such as esophagitis, gastritis, Helicobacter pylori, and the presence of goblet cells. Our results show that either pure mucous glands (81%) or mixed mucous/oxyntic-type glands (19%) were present within 1 mm of the squamocolumnar junction in all of the patients (100%) in this study. Patients with mixed mucous/oxyntic glands located <1 mm from the squamocolumnar junction were more likely to have goblet cells than were patients with mucous glands alone, but they did not differ with respect to any other feature, including patient age. However, both active esophagitis and increased inflammation in the cardia correlated positively with a longer length of pure mucous glands in the gastroesophageal junction region. Of the cases with inflammation (carditis), eosinophils correlated with the presence of active esophagitis (a histologic manifestation of gastroesophageal reflux disease), whereas increased lymphocytes correlated with chronic H. pylori gastritis. In summary, a small amount of pure mucous-type glands is present in the cardia in most pediatric patients, a finding that supports a congenital origin for this type of epithelium. However, our finding of an association between length of mucosa occupied by pure mucous glands and active esophagitis suggests that injury and repair related to gastroesophageal reflux disease may contribute to expansion of the zone occupied by cardia-type mucous glands.

Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis.

Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by the presence of chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with CC also have a thickened subepithelial collagen layer. We have noted, anecdotally, that biopsy specimens from some patients with CC or LC contain certain histologic features, such as Paneth cell metaplasia (PM), that are normally seen in inflammatory bowel disease (IBD), or other types of healed colitis, and thus may cause diagnostic difficulty. Therefore, the purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with CC or LC. Five hundred thirty-one routinely processed hematoxylin and eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed CC (79 patients, male/female ratio: 14/65, mean age: 60 yr) or LC (71 patients, male/female ratio: 13/58, mean age: 55 yr) were evaluated in a blinded fashion for a variety of histologic features, including active crypt inflammation (cryptitis +/- crypt abscess), surface ulceration, Paneth cell metaplasia, crypt architectural irregularity, number of intraepithelial lymphocytes, and thickness of the subepithelial collagen layer (CC only). The results were compared between CC and LC and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period. Active crypt inflammation was a common finding in both groups, seen in 24 of 79 CC patients (30%) and 27 of 71 LC patients (38%). Surface ulceration was not seen in any of the LC biopsies but was present in 2 of 79 (2.5%) CC patients. Paneth cell metaplasia was frequent in both groups and significantly more common in CC compared with LC patients. Forty-four percent of CC patients, but only 9 of 63 (14%) of LC patients had Paneth cell metaplasia (p <0.001). Crypt architectural irregularity, although rare, was present in 6 of 79 patients with CC (7.6%) and 3 of 71 (4.2%) patients with LC. In patients with CC, the presence of Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (p <0.001) and a higher frequency of bowel movements (>3 bowel movements/day) (p = 0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (p = 0.04) and was present in the only two patients who had positive stool cultures (one each for and ). However, none of the other histologic findings correlated with any of the other clinical or endoscopic features, such as type of symptoms, stool consistency, type of medical treatment, associated autoimmune diseases or outcome (complete, partial, or no resolution) in either group of patients. Pathologists should be aware that some histologic features normally associated with IBD such as crypt irregularity and neutrophilic cryptitis and crypt abscesses are not uncommon in patients with CC or LC and that the presence of one or more of these features should not necessarily be interpreted as evidence against either of these diagnoses.

The terminal ileum is affected in patients with lymphocytic or collagenous colitis.

Lymphocytic colitis (LC) and collagenous colitis (CC) are diseases characterized by the presence of marked intraepithelial lymphocytosis. Both of these disorders affect primarily the colon. However, involvement of the distal small intestine has not been systematically studied. The purpose of this study was to evaluate the type and degree of intraepithelial lymphocytosis in the terminal ileum of patients with LC or CC. Terminal ileal mucosal biopsies from 22 patients with LC (male/female ratio 0.22, mean age 47 years) and 23 with CC (male/female ratio 0.43, mean age 54 years) were evaluated for the number of intraepithelial lymphocytes (IEL) per 100 epithelial cells (EC) both in the villi and crypts. The results were compared with 30 patients with inflammatory bowel disease (16 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) and 24 patients (male/female ratio 0.33, mean age 44 years) without colonic pathology as normal controls. None of the patients had celiac sprue. Paired terminal ileum and colonic mucosal biopsies from 6 patients with LC, 4 with CC, 5 with CD, 5 with UC, and 10 normal controls were also immunohistochemically stained with monoclonal antibodies to CD3, CD8, CD20, and a class II MHC antigen (LN3-HLA-DR). In the villi the IEL count/100 EC was 11.8 +/- 1.8 in LC and 10.3 +/- 1.9 in CC (p = 0.3). These values were both significantly higher than in CD (2.8 +/- 0.4, p <0.001), UC (3.1 +/- 0.4, p <0.001), or normal controls (2.2 +/- 0.2, p <0.001). In the crypts the IEL count was 3.8 +/- 0.5 in LC and 3.2 +/- 0.5 in CC (p = 0.3). These values were also significantly higher than in CD (2.3 +/- 0.4, p = 0.02), UC (2.1 +/- 0.3, p = 0.02), or normal controls (1.5 +/- 0.2, p <0.001). The presence of >5 IELs/100 EC in terminal ileum biopsies was highly specific for LC and CC (specificity 98%, sensitivity 73% and 56% for LC and CC, respectively). The IEL phenotype was similar in all groups of patients and in the ileum and colon of individual patients. Intraepithelial lymphocytes were CD3+, CD8+, CD20-, and LN3-HLA-DR-, indicative of a suppressor T-cell phenotype. Intraepithelial lymphocytosis occurs in the terminal ileum in patients with LC or CC and may be helpful in diagnosing these conditions and distinguishing LC or CC from CD or UC in diagnostically difficult cases. The results suggest that the terminal ileum may be involved by a similar pathogenic process as the colon in LC and CC.

Competency-based residency training in pathology: challenges and opportunities.

The Accreditation Council for Graduate Medical Education (ACGME) is requiring that all medical specialties adopt a new paradigm for residency education: competency-based residency education. Competency-based education includes not only the acquisition of knowledge and the demonstration of safe medical practice, but also competency in practice-based learning, practice improvement, interpersonal skills and communication, professionalism, and an awareness of pathology's role in a larger health care system. Implementation of this new training program will require new educational resources and the implementation of new faculty and resident skills and incentives.

High-frequency probe ultrasonography has limited accuracy for detecting invasive adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma: a case series.

AIM: To evaluate prospectively the accuracy of preoperative high-frequency (20 MHz) probe ultrasonography (HFPUS) for detecting invasive cancer in patients referred for esophagectomy because of an endoscopic biopsy diagnosis of high-grade dysplasia (HGD) or intramucosal carcinoma (ICA) in Barrett's esophagus (BE). PATIENTS AND METHODS: Nine consecutive male patients (median age of 69 yr) who were referred for esophagectomy for HGD or ICA in BE agreed to participate. We performed conventional upper gastrointestinal endoscopy followed by HFPUS using a through-the-scope ultrasound probe (20 MHz), and we compared our preoperative findings with the pathologist's findings in the resected esophageal specimens. RESULTS: There was complete agreement between the postoperative pathological findings and the preoperative HFPUS findings in only 4 of the 9 patients. HFPUS resulted in two false-negative diagnoses of esophageal cancer (both had T1 lesions in the resected specimens), one false-positive diagnosis of esophageal cancer, and two errors in tumor staging (1 understaged, 1 overstaged). CONCLUSIONS: HFPUS has limited accuracy for identifying invasive cancer in patients found to have HGD or IMC in BE. Pending further refinements in technology, clinical management decisions in such patients should not be based solely on the results of HFPUS.

Eosinophils in the esophagus--peptic or allergic eosinophilic esophagitis? Case series of three patients with esophageal eosinophilia.

OBJECTIVES: Scattered eosinophils in the distal esophagus traditionally provide the hallmark for peptic esophagitis, but the upper limit of eosinophils and the longitudinal extent of peptic inflammation along the esophagus are unknown. Recently, adults and children with upper intestinal symptoms and >20 eosinophils/high-power field (eos/HPF) have been given the diagnosis of allergic esophagitis. Standardized diagnostic criteria for allergic esophagitis are lacking and the isolated finding of large numbers of eosinophils in the squamous epithelium has been used as the defining feature. We cared for three patients with symptoms and endoscopic features of esophagitis with >20 eos/HPF in their esophageal mucosa. Symptoms, endoscopic features, and histologic findings resolved after 2 months of proton pump inhibitor (PPI) treatment. The aim of this case series is to demonstrate that features thought to be consistent with a diagnosis of allergic esophagitis are also observed in peptic esophagitis. METHODS: A retrospective chart review of three patients with esophagitis (>20 eos/HPF) whose symptoms and eosinophilia resolved with PPI treatment was performed. Esophageal biopsies were reviewed in a blinded manner by one pathologist. RESULTS: Patients (aged 14, 25, and 5 yr) presented with dysphagia, food impaction, and vomiting. Endoscopic features included white exudates and linear furrows. None of the patients received antiallergic treatments or dietary eliminations prior to endoscopy. Following treatment with PPIs alone, all patients became asymptomatic and endoscopic findings reverted to normal. In all three patients, pre- and post-PPI treatment eosinophil numbers/HPF decreased to normal/near normal (37 to 1, 21 to 3, and 52 to 0 eosinophils/HPF in patients 1, 2, and 3, respectively). CONCLUSION: Large numbers of eosinophils can be seen in peptic esophagitis. This histologic finding must be interpreted in the context of the clinical setting in which it is obtained.

Celiac disease: a progress report.

Celiac disease (CD) has a wide range of clinical presentations and is being diagnosed with increasing frequency in patients in the 4th and 5th decades of life. The diagnosis of CD is confirmed by a combination of clinical, serological, and morphological findings associated with a response to a gluten-free diet. In small-bowel mucosal biopsy specimens, abnormalities range from minimal (increased villous intraepithelial lymphocytes only) to severe (complete villous blunting with crypt hyperplasia). Recognition of CD is important because appropriate therapy of this condition will obviate the risk of its severe complications.

Intestinal metaplasia of the gastric cardia: A prospective study with enhanced magnification endoscopy.

OBJECTIVE: There are no endoscopic features that distinguish intestinal metaplasia of the cardia (CIM) from the normal cardia. Biopsy specimens are therefore randomly obtained from normal-appearing mucosa with significant potential sampling errors. Enhanced magnification endoscopy involves the combined use of magnification endoscopy with acetic acid instillation. This study assessed the value of enhanced magnification endoscopy in detecting CIM. METHODS: Patients undergoing elective upper endoscopy were invited to participate in the study. Patients were included if the squamocolumnar junction and the esophagogastric junction were judged to be at the same level. Enhanced magnification endoscopy was performed with 3% acetic acid instillation. Standard endoscopy was followed by magnification endoscopy and repeated after acetic acid spraying. Surface patterns were characterized before and after acetic acid spraying. The observed surface patterns were compared with histological results obtained from a single targeted biopsy specimen of each pattern. RESULTS: The overall prevalence of CIM was 34.8% (86/247 patients). After excluding 52 patients because of endoscopic evidence of Barrett's esophagus, 195 patients were eligible for participation in the study. In the study group, CIM was detected in 86 patients (44.1%) in targeted biopsy samples. No dysplasia was identified. Enhanced magnification endoscopy detected four different patterns of the mucosal surface: I) round pits, II) reticular, III) villous, and IV) ridged. The yields of detection of intestinal metaplasia according to endoscopic patterns were I) 0%, II) 5.3% (odds ratio = 0.05), III) 57.7% (odds ratio = 7.5, p = 0.0001), and IV) 95.8% (odds ratio = 42.8, p = 0.0001). CONCLUSIONS: CIM is more common than previously reported. Enhanced magnification endoscopy identifies two characteristic endoscopic patterns, villous (pattern III) and ridged (pattern IV), with outstanding clarity and resolution that correlate with histological identification of CIM with a single targeted biopsy sample. Enhanced magnification endoscopy will permit longitudinal studies of an entity that can be identified endoscopically.

Sequential clinical and histopathological changes in collagenous and lymphocytic colitis over time.

We conducted this retrospective study to evaluate the relationship between symptoms, histological findings, and treatment of collagenous (CC) and lymphocytic colitis (LC). We identified 19 CC and 12 LC patients having multiple colonoscopic procedures with colonic biopsies during their course of illness. A detailed histological review of all biopsies was performed. Clinical history, including symptoms and medications, was obtained in 25 of the 31 patients and was correlated with their histological findings. In all, 25% of the CC patients and 50% of the LC patients who had biopsies prior to their definitive diagnosis had the pathognomonic histological features on their prior biopsies to some extent (but were not recognized by the pathologists); however, these features were more pronounced on the biopsies from the procedure that established the diagnosis. Nonetheless, 10 of 12 such patients with clinical data available had symptoms and were being treated at the time of prior biopsies. Assessment of the relationship among histological, clinical and therapeutic data showed no association between symptoms or histological findings and treatment with any medication. In summary, in this sample of CC and LC patients, symptoms often precede fully developed histological features. No change in symptoms or histological findings was found to be associated with medication.