The role of eosinophils in inflammatory bowel disease.
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Colitis, Ulcerative↗
Biomedical subjects
R H Riddell
Publications and source records attributed to R H Riddell.
Perianal apocrine adenocarcinoma arising in a benign apocrine adenoma; first case report and review of the literature.
Benign apocrine lesions have been described in the anogenital region, although according to the World Health Organisation convincing examples of anal apocrine adenocarcinomas have not been published. This report describes the case of an invasive apocrine adenocarcinoma arising in a benign adenoma in the perianal region of a 45 year old woman. The origin and invasiveness are supported by histological and immunohistochemical studies.
Adenocarcinoma↗
Detection of species-specific helicobacter ribosomal DNA in intestinal biopsy samples from a population-based cohort of patients with ulcerative colitis.
The inflammatory bowel diseases are considered an abnormal host immune response to an environmental stimulus. Evidence suggests a role for intestinal bacteria in initiating and/or providing an ongoing stimulus for inflammation in inflammatory bowel disease. Helicobacter pylori is the major cause of active chronic gastritis and peptic ulcers in humans and has been linked to gastric carcinoma and lymphoma. Studies in various animal models, particularly mice, have identified enterohepatic Helicobacter species that are capable of causing hepatitis and enterocolitis. We hypothesize that Helicobacter species may have a role in maintaining inflammation in humans with inflammatory bowel disease. In order to investigate this, biopsy specimens were obtained from patients with and without inflammatory bowel disease. DNA was extracted from the tissues and subjected to PCR with primers designed to detect the ribosomal DNA of members of the Helicobacter species. DNA from six biopsy samples from 60 inflammatory bowel disease patients tested positive. This included 5 of 33 ulcerative colitis patients that were positive compared to 0 of 29 age-matched controls (P < 0.04). Sequencing of the bands produced by PCR amplification revealed >or=99% homology with H. pylori. These results indicate that a member of the Helicobacter species may be involved in some cases of ulcerative colitis.
Base Sequence↗
Indeterminate colitis.
Indeterminate colitis (IC) originally referred to those 10-15% of cases of inflammatory bowel disease (IBD) in which there was difficulty distinguishing between ulcerative colitis (UC) and Crohn's disease (CD) in the colectomy specimen. However, IC is increasingly used when a definitive diagnosis of UC or CD cannot be made at colonoscopy, in colonic biopsies or at colectomy. The diagnostic difficulties may explain the variably reported prevalence of IC. Clinically, most patients with IC evolve to a definite diagnosis of UC or CD on follow up. The role of ancillary tests in the distinction of UC from CD is reviewed. The low sensitivity of serological markers limits their usefulness. Other tests include upper endoscopy and magnetic resonance imaging. The definition of IC may not be a purely histological one derived from resected specimens, but rather a clinicopathological one. This review offers some personal observations and viewpoints, and proposes an approach to some of the relatively more esoteric combinations of findings.
Colectomy↗
Loss of CD117 (c-kit)- and CD34-positive ICC and associated CD34-positive fibroblasts defines a subpopulation of chronic intestinal pseudo-obstruction.
Chronic idiopathic intestinal pseudo-obstruction is a syndrome in which symptoms of intestinal obstruction are present in the absence of mechanical obstruction. Lack of normal pacemaker activity, usually generated by the interstitial cells of Cajal (ICC), could account for the apparent obstruction. ICC are normally located around and between the myenteric plexus ganglia and within muscle and also in the deep muscular plexus of the small bowel and the submuscular plexus of the large intestine, just within the circular muscle. ICC can be demonstrated immunohistochemically with CD117 (c-kit) as well as with CD34, although this is less specific. CD34 also stains a population of fibroblasts that are intimately associated with ICC. To determine whether there is a relative deficiency of ICC and CD34-positive fibroblasts in patients with chronic idiopathic intestinal pseudo-obstruction, tissue from 30 patients of large intestine and eight patients with small intestine pseudo-obstruction was obtained. Controls (large intestinal specimens from 12 patients, small intestinal specimens from six patients) were chosen from resections for Crohn's disease and colorectal neoplasia, both with and without dilatation. Examination of pseudo-obstruction cases identified 10 patients (nine large intestinal and one small intestinal) in which both CD117 and CD34 were absent or severely reduced in all three of the examined areas. In contrast, the control cases, including those with preobstructive dilatation, showed relatively constant ICC staining. These results suggest that there is a proportion of pseudo-obstruction cases in which the ICC are markedly reduced. These results also demonstrate that, in these cases, loss of the kit immunoreactivity is correlated with the loss of CD34 staining: this indicates that both the ICC and the CD34-positive fibroblasts associated with the ICC are absent. These findings will allow surgical pathologists to identify this subpopulation of patients with CIIP using tissue obtained by laparoscopic biopsy of the muscularis propria or surgical resection.
Antigens, CD34↗
Utilization of cytokeratins 7 and 20 does not differentiate between Barrett's esophagus and gastric cardiac intestinal metaplasia.
Long segment Barrett's esophagus (LSBE) is a recognized risk factor for the development of esophageal dysplasia and carcinoma. However, the risk of dysplasia arising within intestinal metaplasia below a normal-appearing Z-line (i.e., in native cardiac mucosa) is unknown. Regular endoscopic surveillance is required in patients with LSBE and is frequently performed in short segment BE (SSBE), but the need for surveillance in cardiac intestinal metaplasia (CIM) is unknown. Unfortunately IM arising in SSBE and immediately below a normal Z-line can be indistinguishable histologically on H&E stains. Previous reports suggest that the appearance of superficial CK20 immunohistochemical staining accompanied by intermediate and deep CK7 positivity is characteristic of BE, whereas CIM specimens show superficial and deep CK20 positivity and weak to absent CK7 staining. We hypothesized that CK7/20 immunostaining of metaplastic biopsies from the esophagus and stomach would allow complete differentiation of these two entities when correlated with the endoscopic appearance. We undertook an evaluation of gastric and esophageal specimens to determine whether these characteristics were valid. Cases of both BE (long and short segment) and CIM, as well as cases of gastric cardiac biopsies lacking IM, were evaluated for CK7 and CK20 and correlated with the endoscopic appearance. We observed that, although the "Barrett's" pattern of CK7/20 was maintained for many cases of BE, the sensitivity and specificity were only moderate (65% and 56%, respectively). The pattern of staining for the CIM was variable, i.e., some cases showed a CK7/20 Barrett's pattern despite a normal appearance at endoscopy. The differences between this and previous studies may be due to inaccurate visualization of SSBE on endoscopy, the development of very early SSBE cases, inter-observer variability, fixation differences, or antibody differences. Whatever the cause of the differences, if results between laboratories are not comparable, CK7/20 immunostaining cannot be used to differentiate reliably between IM present in biopsy specimens taken from above versus below the Z-line. However, further studies should be performed to determine whether the presence or absence of a Barrett's pattern of CK7/20 immunostaining could predict progression to dysplasia or carcinoma.
Barrett Esophagus↗
Leiomyomatosis-like lymphangioleiomyomatosis of the colon in a female with tuberous sclerosis.
Smooth muscle lesions of the large bowel, excluding the rectum, are generally rare, and diffuse smooth muscle lesions, termed leiomyomatosis, are even rarer. In this report, we document, for the first time, leiomyomatosis-like lymphangioleiomyomatosis (LAM) of the ascending, transverse, and descending colon in association with bilateral renal angiomyolipoma (AML) in a 30-year-old Chinese female with tuberous sclerosis complex (TSC). She presented with protracted constipation for which a colectomy was performed. Histology disclosed multiple confluent nodular CD34 and CD117 negative smooth muscle proliferation within the large bowel wall, whereas the renal biopsy revealed typical features of AML. Interestingly, the epithelioid smooth muscle cells of both the colonic and renal lesions were HMB45 positive, suggesting that leiomyomatosis-like LAM of the colon, pulmonary LAM and AML are closely related entities. The patient remained free of complications for the last five years after surgery. Leiomyomatosis-like LAM of the large bowel probably represents another manifestation of the tendency of TSC to be associated with proliferative lesions.
Actins↗
The pathology of epithelial pre-malignancy of the gastrointestinal tract.
This chapter deals with pre-malignant epithelial lesions of the gastrointestinal tract that have the potential to become cancers. Pre-malignant lesions are divided into two types: those characterized by dysplastic mucosa and those without dysplasia. Examples of the two types are present in the oesophagus, stomach and intestine. In the oesophagus, dysplasia of the squamous epithelium is a precursor to squamous carcinoma. There are differences in interpretation between Western and Japanese pathologists in the diagnosis of oesophageal squamous lesions. Dysplasia in Barrett's oesophagus is regarded as a precursor of adenocarcinoma. The goal of endoscopic surveillance in Barrett's mucosa is the detection of high-grade dysplasia. There are several problems with our current knowledge of high-grade dysplasia and controversies regarding its management. There are differences in the interpretation of biopsies of gastric epithelial dysplasia between Japanese and Western pathologists. In the colon, pre-malignant lesions include dysplasia seen in inflammatory bowel disease and colonic adenomas. The most significant predictor of the risk of malignancy in patients with inflammatory bowel disease is the presence of dysplasia in colonic biopsies. Because of the similarity of neoplasia throughout the gastrointestinal tract, there have been attempts to unify its classification, terminology and diagnostic criteria internationally, the most recently proposed modified classification of gastrointestinal neoplasia being the Vienna classification. Dysplasia of the columnar mucosa has a similar appearance in Barrett's oesophagus, the stomach and the colon. Criteria for its histological diagnosis and grading are reviewed, with an emphasis on areas of diagnostic difficulty such as interobserver variation, and discrepancies between Western and Japanese pathologists. Implication of the presence of dysplasia that are specific to each organ site are discussed, highlighting weaknesses and controversies in current knowledge.
Carcinoma↗
Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system.
The relationship between the development of the enteric nervous system and interstitial cells of Cajal (ICC) in the human small intestine was investigated in a full-term infant who presented with intestinal pseudo-obstruction. Immunohistochemistry revealed absence of enteric nerves and ganglia but abundant c-Kit immunoreactivity associated with Auerbach's plexus (ICC-AP). However, c-Kit immunoreactivity associated with the deep muscular plexus (ICC-DMP) and intermuscular ICC was absent. Electron microscopy showed ICC-AP with a normal ultrastructure; ICC-DMP were seen but were severely injured, suggesting degeneration. In vitro recording of intestinal muscle showed slow wave activity as well as response to cholinergic stimulation. Fluoroscopic examination of the small bowel showed a variety of motor patterns, including rhythmic, propagating contractions. In conclusion, total absence of enteric nerves was associated with absence of normal ICC-DMP. However, a normal musculature, including a network of ICC-AP, allowed for generation of rhythmic, propagating contractile activity, suggesting the presence of functional motor activity.
Biological Clocks↗
Gastric acid secretory response in Helicobacter pylori-positive patients with duodenal ulcer disease.
BACKGROUND: Patients with duodenal ulcer (DU) have an increased parietal cell mass and sensitivity to secretagogues, with increased acid output. AIM: To determine the effect of Helicobacter pylori eradication on parietal cell sensitivity and gastric acid secretion. SUBJECTS AND METHODS: Twenty-five H pylori-positive DU patients and 18 H pylori-negative healthy volunteers were studied. Serum H pylori immunoglobulin G, basal acid output and acid secretory response to graded doses of pentagastrin were determined before and after treatment, at six months and at one year. Subjects were randomly assigned to ranitidine or sucralfate treatment for six weeks, and all DU patients received bismuth subsalicylate, metronidazole and tetracycline for the first two weeks. RESULTS: H pylori was eradicated in 66% of patients receiving sucralfate and 92% receiving ranitidine. Compared with healthy volunteers, DU patients demonstrated a 2.7-fold greater basal acid output, a 1.3-fold greater peak acid output, significantly higher acid output for each dose of pentagastrin and a 1.38-fold increase in the area under the pentagastrin dose acid response curve. Cure of H pylori, irrespective of ulcer healing regimen, resulted in a gradual decrease in acid secretory capacity with basal acid output, peak acid output and area under the pentagastrin dose acid response curve returning to healthy volunteer levels by one year. No demonstrable differences were observed in parietal cell sensitivity in all subjects before or after treatment. These data suggest that disturbances in acid secretion in H pylori-positive DU patients are not due to an increased parietal cell sensitivity to pentagastrin but rather due to an increased parietal cell mass with increased capacity to secrete acid, which gradually resolves following cure.
Adult↗
Differences in diagnostic criteria for esophageal squamous cell carcinoma between Japanese and Western pathologists.
BACKGROUND: Large discrepancies have been found between Western and Japanese pathologists in the diagnosis of adenoma/dysplasia versus carcinoma for gastric and colorectal glandular lesions. It is important to determine whether similar differences exist in the diagnosis of esophageal squamous lesions. METHODS: Eleven expert gastrointestinal pathologists from Japan, North America, and Europe individually reviewed a set of microscopic slides containing 21 sections of biopsies and corresponding endoscopic mucosal resection specimens from Japanese patients with superficial esophageal squamous neoplastic lesions. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS: Invasion was the most important diagnostic criterion of carcinoma for the Western pathologists whereas nuclear and structural features were more important for the Japanese pathologists. For two sections showing low grade dysplasia according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in the other. For nine sections with high grade dysplasia according to the Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in two cases and definite carcinoma in seven cases. For six sections with suspected carcinoma according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in five cases. Four sections showed definite carcinoma according to both the Western and Japanese pathologists. Thus, there was agreement among the Western and Japanese pathologists for only 5 of the 21 sections (kappa value, 0.04). However, when high grade dysplasia, noninvasive carcinoma, and suspected carcinoma were grouped together, the agreement was excellent (19 of the 21 sections; kappa value, 0.75). CONCLUSIONS: In Japan, esophageal squamous cell carcinoma is diagnosed mainly based on nuclear criteria, even in cases judged to be noninvasive low grade dysplasia in the West. This difference in diagnostic practice may contribute to the relatively high incidence rate and good prognosis of superficial esophageal carcinoma in Japan. To improve the comparability of research data, the authors recommend that high grade dysplasia, noninvasive carcinoma, and suspected carcinoma be grouped together into one category of "noninvasive high grade neoplasia." [See editorial on pages 969-70, this issue.]
Aged↗
Gastrointestinal stromal tumors may originate from a subset of CD34-positive interstitial cells of Cajal.
Most gastrointestinal stromal tumors (GISTs), a subgroup of mesenchymal neoplasms of the gut wall, express both Kit (CD117) and CD34 proteins. It has been suggested that GISTs originate from or differentiate into interstitial cells of Cajal (ICC), after several reports indicated that ICC are likely the only cells in the gut which express both Kit and CD34. ICC are among the few cell types resident in the gut which express Kit, together with mast cells. However, the question whether or not ICC express CD34 is currently disputed. Using single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) on cultured murine intestinal cells, single ICC were selected by morphology and tested for the expression of c-kit and CD34 mRNA. Most ICC were only c-kit-positive, however a subset (7 out of 43) were double positive for both c-kit and CD34. In the human small intestine, sequential immunohistochemical staining for Kit and CD34 proteins on the same 3-microm sections showed that some of the ICC surrounding Auerbach's plexus and ICC within the circular muscle layer of the small intestine were positive for both Kit and CD34. In addition, CD34(+)Kit(-) cells were seen adjacent to ICC. These data from two different techniques indicate that ICC can be double positive for Kit and CD34. Thus, GISTs with the Kit(+)CD34(+) phenotype may arise from a subpopulation of CD34(+) Kit(+) ICC.
Animals↗
Recommendations for the reporting of resected esophageal carcinomas. Association of Directors of Anatomic Surgical Pathology.
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Esophageal Neoplasms↗
Gastric dysplasia: the Padova international classification.
A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.
Adenocarcinoma↗
The Vienna classification of gastrointestinal epithelial neoplasia.
BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.
Adenoma↗
Colonoscopy plus biopsy in the inflammatory bowel diseases.
Colon biopsies are critical in helping to diagnose diarrhea, to distinguish different forms of colitis, to determine the extent of disease, and to determine if neoplasia has arisen in the setting of chronic colitis. Table 3 summarizes the recommended locations and numbers of biopsies for different scenarios. Some of the technical aspects pertaining to those are also discussed elsewhere in this issue. Colon biopsies in some instances can be definitive, but this usually requires the appropriate clinical scenario. For instance, to appreciate that segmental granulomatous colitis is Crohn's disease and not the much rarer colonic sarcoidosis requires ancillary clinical information. Often colon biopsies may definitively reveal an abnormality, but the findings may be nonspecific in regards to a definitive diagnosis. To use colon biopsies most appropriately in patient management and to get the most mileage from them usually requires frequent clinician-pathologist interaction, often repeat endoscopy with [table: see text] biopsies at a different time, and the assessment of the biopsies in the clinical context.
Biopsy↗
Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis.
BACKGROUND: Inflammatory bowel disease (IBD)--and Crohn's disease (CD) and ulcerative colitis (UC) in particular--could be more reliably diagnosed by using biopsy criteria incorporating the colorectal distribution of specific histologic features. The aim of this study was to elucidate criteria distinguishing IBD from other forms of colitis (non-IBD), and CD from UC on the basis of multiple colorectal biopsies. METHODS: We examined multiple biopsy specimens (mean, 6.1) from 299 consecutive Japanese subjects with active colitis and performed multiple logistic regression analyses on 70 histologic features, from which 2 equations were constructed for the probabilities (P(IBD) and P(CD)) of a) IBD (versus non-IBD), and b) CD (versus UC), respectively, being present. On the basis of a receiver-operating characteristic curve, we determined four cut-off values for P(IBD) and constructed the criteria, consisting of the five categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. The criteria for CD versus UC were constructed in a similar manner. Their validities were evaluated using 132 Canadian subjects. RESULTS: The statistically significant histologic features were as follows: for IBD, crypt architectural abnormalities, basal plasmacytosis with severe chronic inflammation, and distal Paneth cell metaplasia; for CD, segmental crypt architectural abnormalities and mucin depletion, mucin preservation at the active sites, and focal chronic inflammation without crypt atrophy. In the categories of probable IBD and probable non-IBD, both sensitivities and specificities exceeded 97%. Probable CD and probable UC showed high specificities of more than 97%, and their sensitivities were 94% and 89%, respectively. Kappa statistics showed these criteria to be sufficiently reproducible. CONCLUSIONS: Specific histological features together with their distribution can reliably diagnose IBD, distinguish CD from UC, and provide an estimate of the probability of the underlying disease being present.
Adult↗
Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors.
Interstitial cells of Cajal (ICC) are implicated in the regulation of gut peristalsis and are immunostained by antibodies against Kit (CD117), a tyrosine kinase receptor. Most gastrointestinal mesenchymal tumors (GIMTs) are of uncertain histogenesis, although many are CD34-positive. CD34 was found to colocalize with vimentin (Vim) and the Kit-positive networks of cells within and around neural plexi, indicating that ICC can be Vim- and CD34-positive. ICCs appear to be the only Kit+CD34+Vim+ cell in the gut. Formalin-fixed, paraffin-embedded tissues from 43 GIMTs were immunostained for Kit, CD34, Vim, PGP 9.5 (PGP, a neural marker), muscle-specific actin (MSA), and other markers including desmin (Des). Eight tumors were myoid (MSA+Des+Vim-Kit-CD34-), and one was a schwannoma (PGP+S100+Vim+Kit-CD34-), but 34 tumors were of uncertain histogenesis (gastrointestinal stromal tumors, GIST), exhibiting neither a complete myoid nor a schwannian immunophenotype. All 34 were Vim+, and 33/34 were either Kit (n = 30) or CD34 (n = 23) immunoreactive. Of these 34 GIST, 24 were negative for all myoid and neural markers, 6 were PGP+S100-, and 4 were MSA+Des-. The Kit+CD34+Vim+ immunophenotype of GIST suggests that they originate from, or have differentiated into, ICC-like cells; the term ICC tumor (ICCT) is suggested. Kit is a more sensitive marker than CD34 for ICCT, but both are required in tumor identification. All clinically malignant GISTs were pathologically malignant (size, mitoses) but also showed loss of either CD34 or Kit. "Blind" examination of electron micrographs in 10 tumors showed them to be heterogeneous. Some had features seen in normal ICC, but cells could not be positively identified as being adult ICC. GIMT may therefore be classifiable into those with pure myoid, schwannian (or neural) differentiation, but the majority are of ICC origin or show ICC differentiation immunophenotypically (ICCT).
Biomarkers, Tumor↗