John H. Yardley

Classification and grading of Gastritis: The updated Sydney system

The Sydney System for the classification of gastritis emphasized the importance of combining topographical, morphological, and etiological information into a schema that would help to generate reproducible and clinically useful diagnoses. To reappraise the Sydney System 4 years after its introduction, a group of gastrointestinal pathologists from various parts of the world met in Houston, Texas, in September 1994. The aims of the workshop were (a) to establish an agreed terminology of gastritis; (b) to identify, define, and attempt to resolve some of the problems associated with the Sydney System. This article introduces the Sydney System as it was revised at the Houston Gastritis Workshop and represents the consensus of the participants. Overall, the principles and grading of the Sydney System were only slightly modified, the grading being aided by the provision of a visual analogue scale. The terminology of the final classification has been improved to emphasize the distinction between the atrophic and nonatrophic stomach; the names used for each entity were selected because they are generally acceptable to both pathologists and gastroenterologists. In addition to the main categories and atrophic and nonatrophic gastritis, the special or distinctive forms are described and their respective diagnostic criteria are provided. The article includes practical guidelines for optimal biopsy sampling of the stomach, for the use of the visual analogue scales for grading the histopathologic features, and for the formulation of a comprehensive standardized diagnosis. A glossary of gastritis-related terms as used in this article is provided.

Increased risk of cancer in the Peutz-Jeghers syndrome

The Peutz-Jeghers syndrome is an autosomal dominant hereditary disease characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous melanin deposits. The frequency of cancer in this syndrome has not been studied extensively. Therefore, we investigated 31 patients with the Peutz-Jeghers syndrome who were followed from 1973 to 1985. All cases of cancer were verified by histopathological review. Cancer developed in 15 of the 31 patients (48 percent)--gastrointestinal carcinomas in 4, nongastrointestinal carcinomas in 10, and multiple myeloma in 1. In addition, adenomatous polyps of the stomach and colon occurred in three other patients. The cancers were diagnosed when the patients were relatively young, but after the Peutz-Jeghers syndrome had been diagnosed (interval between diagnoses, 25 +/- 20 years; range, 1 to 64). According to relative-risk analysis, the observed development of cancer in the patients with the syndrome was 18 times greater than expected in the general population (P less than 0.0001). Our results suggest that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.

Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome.

Abstract We examined 134 members of 16 families with Gardners syndrome for pigmented ocular fundus lesions. Of 41 patients with documented Gardners syndrome, 37 (90.2 percent) had such lesions. The lesions were bilateral in 32 of the patients (78.1 percent) and in 2 of 42 controls (4.8 percent). Twenty (46.5 percent) of 43 first-degree relatives at 50 percent risk for Gardners syndrome had bilateral pigmented fundus lesions, indicating that they had probably inherited the abnormal gene. The presence of bilateral lesions, multiple lesions (more than four), or both appeared to be a specific (specificity, 0.952) and sensitive (sensitivity, 0.780) clinical marker for Gardners syndrome. The lesions are probably congenital; they were observed in a three-month-old baby at risk. The multiplicity of the pigmented fundus lesions and their association with diffuse disturbances of the retinal pigment epithelium in the same eye suggest a widespread expression of the abnormal gene in the retinal pigment epithelial ...

Chronic colitis with thickening of the subepithelial collagen layer (collagenous colitis): Histopathologic findings in 15 patients

The histopathologic features of collagenous colitis were studied in 14 women and one man. All but one patient presented with chronic watery diarrhea: 10 had a history of thyroid disease or unspecified arthritis. All 15 patients showed characteristic thickening of the subepithelial collagen layer (SCL) in colorectal biopsy specimens, but in the distal colorectum the thickening was sometimes absent or borderline. Patchy or diffuse injury to the surface epithelium was seen in all cases and was independent of SCL thickening. The injured surface epithelium was infiltrated by lymphocytes and variably by eosinophils and neutrophils, causing it to resemble the surface epithelial injury seen in the small intestine in celiac disease. Crypts were commonly infiltrated by lymphocytes but without associated epithelial injury. The lamina propria in all patients was expanded by lymphocytes, plasma cells, and eosinophils. Neutrophilic cryptitis was seen in seven patients but was usually sparse. Watery diarrhea abated in eight patients treated with corticosteroids or sulfasalazine and was often paralleled by restoration of surface epithelium, reduction in surface epithelial lymphocytes, diminished SCL thickening, and reduced lamina propria eosinophils. Therapy did not consistently alter other inflammatory changes. The possible role of autoimmunity in collagenous colitis should be investigated because of the following circumstantial evidence: the overwhelming female predominance; the frequent presence of possible immunologically mediated disorders such as thyroid and joint disease; the resemblance of surface epithelial changes to those in celiac disease; and the response to corticosteroids.

Regeneration of Cardiac Type Mucosa and Acquisition of Barrett Mucosa After Esophagogastrostomy

The surgically created squamocolumnar junction in patients who have undergone an esophagogastrostomy after partial esophagogastrectomy provides a unique opportunity to study mucosal regeneration in the setting of gastroesophageal reflux. The pathological and clinical findings in 17 such patients are presented. In each patient the anastomosis had been performed between histologically documented squamous-lined esophagus and gastric fundus. Cardiac type mucosa had regenerated in the region of the anastomosis in 9 patients and was detected as early as 2 months after operation. In addition, 3 patients, 2 of whom had cardiac type mucosa, had acquired Barrett or Barrett-like mucosa on the distal esophagus by 76 to 119 months. Gastroesophageal reflux was prominent in all 3 of these patients. The findings strongly support the hypothesis that the distinctive mucosa of Barretts esophagus develops after reflux-induced ulceration and subsequent mucosal regeneration by immature cells that are derived from cardiac and/or fundic mucosa, and which undergo specialized differentiation in the presence of reflux.

Lymphocytic (microscopic) colitis - Clinicopathologic study of 18 patients and comparison to collagenous colitis

Lymphocytic colitis, formerly called microscopic colitis, is a clinicopathologic syndrome with chronic watery diarrhea and diffuse mucosal inflammatory changes with prominent intraepithelial lymphocytes. The 18 lymphocytic colitis patients studied presented with chronic watery diarrhea at a mean age of 53.8±17 years (±1 SD). Roentgenographic, endoscopic, and culture data were not diagnostic. In patients tested, there was a high prevalence of arthritis (82%) and autoantibodies (50%) but no increase in frequency of histocompatibility antigens associated with well-defined autoimmune disease (DR3, B8). Lymphocytic colitis patients were compared to 21 patients with collagenous colitis. Similarities included age, symptomatology, and nondiagnostic radiographic and endoscopic studies. However, the sex distribution was statistically different, with an equal male-to-female ratio in lymphocytic colitis and female predominance (80%) in collagenous colitis. Other differences included dissimilar histocompatibility phenotypes and collagen band on biopsies of collagenous but not lymphocytic colitis. These findings suggest that lymphocytic and collagenous colitis may be related yet distinct disorders.

Collagenous colitis in setting of nonsteroidal antiinflammatory drugs and antibiotics

Collagenous colitis is a newly recognized diarrheal disorder of unknown etiology (1). Over 80% of patients are middle-aged women with no other known predisposing factors (2). We report unusual presentations of collagenous colitis in two men in whom there was closely linked use of nonsteroidal antiinflammatory drugs and antibiotics.

Hyperplastic polyps of the stomach: Associations with histologic patterns of gastritis and gastric atrophy

Hyperplastic polyps are common gastric lesions characterized by hyperplastic foveolae with variable amounts of inflamed stroma. Their pathogenesis is unknown, but they have been reported to occur in association with various forms of chronic gastritis, particularly autoimmune gastritis and Helicobacter pylori gastritis. Comprehensive histologic evaluation of the background mucosal pathology in patients with hyperplastic polyps has not been previously performed. We studied 160 patients with gastric hyperplastic polyps and characterized endoscopic and histologic features of the polyps (i.e., location, multiplicity, and presence of dysplasia and adenocarcinoma) and the background gastric mucosa (i.e., intestinal metaplasia, dysplasia, carcinoma, and presence and classification of gastritis). Hyperplastic polyps were most common in the antrum (60%) and were multiple in 20% of patients. Focal intestinal metaplasia of the polyp was present in 16% and dysplasia in 4% of patients. Only one patient (0.6%) had adenocarcinoma within the polyp. Evaluation of the surrounding gastric mucosa showed at least focal intestinal metaplasia in 37% of patients, adenoma or low-grade flat epithelial dysplasia in 2%, and synchronous or metachronous adenocarcinoma in 6%. Eighty-five percent of patients had inflammatory mucosal pathology, most commonly active chronic H. pylori gastritis (25%), reactive or chemical gastropathy (21%), and metaplastic atrophic gastritis of the autoimmune (12%) or environmental (8%) type. These results indicate a strong association between various forms of gastritis and the development of hyperplastic polyps and further emphasize the importance of biopsy of the nonpolypoid gastric mucosa during endoscopic examination.

Dysplasia and Dysregulation of Proliferation in Foveolar and Surface Epithelia of Fundic Gland Polyps From Patients With Familial Adenomatous Polyposis

Fundic gland polyps (FGPs) of the stomach are regarded as hamartomatous or hyperplastic/functional polyps that occur sporadically but at increased frequency in patients with familial adenomatous polyposis syndrome (FAP). There is controversy about the histopathology of FGPs, including occurrence of dysplasia. We, therefore, studied dysplasia in 270 sporadic FGPs from 216 patients and 49 FGPs from 24 patients with FAP. We evaluated dysregulation of epithelial proliferation manifested by loss of the normal inverse topographic distribution of Ki-67 proliferation marker and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) using immunohistochemistry in 27 sporadic FGPs and in 22 FGPs from patients with FAP. Dysplasia in foveolar and surface epithelia occurred in 12 of 49 (25%) FGPs in patients with FAP but in only 3 of 270 (1%) of sporadic FGPs (p < 0.000001). Fourteen of 49 (29%) of FGPs from patients with FAP were indefinite for dysplasia, as contrasted with 8 of 270 (3%) sporadic FGPs (p < 0.00001). The normal inverse topographic distribution of Ki-67 and p21(WAF1/CIP1) was maintained in 20 of 22 (91%) of FGPs negative for dysplasia but was lost in all (8 of 8) FGPs with dysplasia and in 11 of 19 (58%) FGPs that were indefinite for dysplasia (p = 0.00001). The results indicate that dysplasia can occur in foveolar and surface epithelia of FGPs, especially in patients with FAP, and often is preceded by dysregulation of epithelial proliferation when the morphologic abnormalities are indefinite for dysplasia.

Pitfalls in the diagnosis of collagenous colitis: Experience with 75 cases from a registry of collagenous colitis at the Johns Hopkins hospital

Collagenous colitis is a relatively rare disorder presenting mainly in middle-aged women as watery diarrhea. Endoscopic and radiographic studies of the colon are usually normal, and diagnosis must be made by biopsy. The characteristic biopsy findings are a combination of increased mucosal inflammation (collagenous colitis) as well as subepithelial collagenous thickening. The mucosal inflammatory changes include increased lamina propria plasma cells, prominent intraepithelial lymphocytes, and in some cases, numerous eosinophils. The collagenous thickening has qualitative as well as quantitative differences from normal, and may be highlighted by Masson trichrome stains. Simply quantitating the thickness of a subepithelial collagen layer is neither adequate nor necessary for the diagnosis of collagenous colitis. Major problems in diagnosing collagenous colitis arise from focusing solely on the subepithelial region without attention to inflammatory changes. For example, tangential sectioning of normal colon results in an artifactually thickened basement membrane, and such cases have been wrongly interpreted as collagenous colitis. If biopsies lack the characteristic inflammatory pattern, a tangentially cut thick basement membrane should be ignored. The key to correct diagnosis of collagenous colitis is analyzing the summation of various inflammatory changes plus subepithelial collagenization, rather than focusing on any single feature in isolation.