Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis-related dysplasia.

AIMS: To assess whether Ki67 and p53 immunostaining may assist the diagnosis and grading of ulcerative colitis-related dysplasia. METHODS AND RESULTS: Location of Ki67 staining and location and intensity of p53 staining were assessed in ulcerative colitis (UC) cases showing the features of high-grade dysplasia (HGD, n = 14), low-grade dysplasia (LGD, n = 22), 'indefinite for dysplasia' (n = 12), or regenerative atypia (RA, n = 22). Good intra- and inter-observer reproducibilities were demonstrated in the performance of these assessments. All the dysplasia cases showed extension of Ki67 staining above the basal third of the crypt. Moderate intensity p53 staining was seen in 10/22 RA cases, but strong intensity p53 staining was seen only in cases of dysplasia. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt. CONCLUSIONS: Restriction of Ki67 staining to the basal third of the crypt appears to exclude a diagnosis of dysplasia whereas strong intensity p53 staining suggests a diagnosis of dysplasia. Restriction of Ki67 or p53 staining to the basal two-thirds of the crypt appears to exclude a diagnosis of HGD.

Diffuse neurofibroma of the ankle.

PURPOSE: To correlate the imaging and histological findings in diffuse neurofibroma. PATIENTS AND METHODS: Retrospective review of clinical, imaging and histological findings in two patients with diffuse neurofibroma. RESULTS: CT demonstrates diffuse infiltration of the deep and subcutaneous fat, isodense to muscle. Magnetic resonance imaging shows extensive infiltration of the subcutaneous and deep fat that envelops tendons and vessels but does not involve bone. Superficial masses enhance homogeneously after intravenous gadolinium. The reticular nature of the deep infiltration is seen on all sequences but is most conspicuous on post-gadolinium T1-weighted images which show tumour enhancement and non-enhancing hypointense soft tissue strands. Magnetic resonance angiography and Doppler ultrasound may show enlarged vessels, high blood flow and vascular pools. CONCLUSION: Diffuse neurofibroma has a characteristic appearance on magnetic resonance that is best shown on post-gadolinium T1-weighted images.

Transjugular intrahepatic portosystemic shunt as a treatment for protein-losing enteropathy caused by portal hypertension.

A case of a 41-year-old man with diarrhea, hypoalbuminemia, and cryptogenic cirrhosis with features of portal hypertension is described. Protein-losing enteropathy was confirmed by analysis of whole-gut lavage fluid, and intestinal inflammation and infection were excluded. Distal duodenal biopsy specimens showed evidence of edematous villi with prominent submucosal vascular and lymphatic vessels. A transjugular intrahepatic portosystemic stent-shunt was inserted, resulting in resolution of both his diarrhea and elevated whole gut lavage fluid protein concentrations. His symptoms recurred and then again improved after shunt thrombosis and parallel shunt placement, respectively. Histological improvement of the villous edema was also noted. This is the first recorded case of protein-losing enteropathy caused by portal hypertension confirmed by successful treatment with transjugular intrahepatic portosystemic stent-shunt.

Intestinal spirochaetosis.

Two cases of intestinal spirochaetosis are described. The first case improved with treatment while the second case improved spontaneously without any intervention. Controversy over treatment and pathogenicity of intestinal spirochaetosis is discussed with review of previous publications.

Epidermal growth factor receptors and oestrogen receptors in the head and neck.

We report a pilot study of the levels of epidermal growth factor receptors (EGFR) in normal and neoplastic tissues of the head and neck. Specimens from 20 consecutive patients undergoing major head and neck surgery showed that squamous cell carcinomas had detectable but widely varying levels of EGFR. EGFR expression was greater in normal salivary gland tissue than in benign salivary neoplasms. Oestrogen receptors were not detected in clinically significant amounts in any of the tumours assayed.

Regressing atypical histiocytosis: report of two cases with progression to high grade T-cell non-Hodgkin's lymphoma.

Two cases of regressing atypical histiocytosis (RAH) are presented. Both patients followed a typical regressing/relapsing course for several years before progression to high-grade neoplasia. In both cases these high-grade tumors were diagnosed as T-cell non-Hodgkin's lymphoma on histopathologic and immunophenotypic grounds, and demonstrated T-cell receptor beta chain (TCR beta) gene rearrangement on Southern blotting. The original cases of RAH were considered to be indolent neoplasms of histiocytic lineage. A single case of a patient with RAH demonstrating TCR beta and gamma gene rearrangements has been described. Our cases lend further weight to the proposition that RAH is a neoplasm of T-cell lineage, and ultimately of aggressive potential. This description accords with current thinking that many of the conditions previously classified as malignant histiocytosis would be better classified as T-cell non-Hodgkin's lymphoma.

The effect of laryngeal irradiation on pharyngoesophageal motility.

The upper esophageal sphincter (UES) receives the full radiation dose during external beam radiotherapy to the adjacent larynx. The aim of the study was to assess the effects, if any, of radical laryngeal radiotherapy on motility patterns in the pharyngoesophageal segment. A strain gauge assembly and a digital manometric recorder were used to assess 19 patients 13 to 71 months after irradiation of T1 to T3 glottic cancer to a central dose of 52.5 to 55.7 Gy in 20 daily fractions. Results were compared with those of 23 healthy controls. Tonic lower esophageal sphincter (LES) pressure, distal peristaltic contraction, tonic UES pressure, and eight parameters of pharyngoesophageal dynamics during water and bread swallows were studied. No difference was found between the two groups in tonic LES pressure, peristaltic amplitude, or tonic UES pressure. Water swallow pharyngoesophageal wave velocity was significantly lower in patients than in controls, and the irradiated group also showed a trend toward increased duration of the distal esophageal peristaltic wave. The reduction in upper esophageal wave velocity was associated with the interval following irradiation. The post-treatment interval was also inversely related to the amplitude of UES after-contraction, and associated with an increase in wave duration throughout the pharyngoesophageal segment. A study of 23 laryngectomy specimens, 5 of which had been removed following radiotherapy, failed to identify pathological features in nerves or muscle which characterised previous laryngopharyngeal irradiation. We conclude that laryngeal irradiation has no effect on upper or lower esophageal sphincter tone but causes an increase in wave duration and a reduction in wave velocity in the pharyngoesophageal segment. These changes are independent of age and sex and are not associated with pathological features like the neural degeneration described in the myenteric plexus of irradiated rectum.

Observer variation in the assessment of dysplasia in ulcerative colitis.

Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only 'fair' or 'moderate'. As expected, agreement over the two categories 'dysplasia' vs 'no dysplasia' was better, ranging from 68% to 84%, and for 'atypia present' (reactive atypia, low- and high-grade dysplasia) vs "no atypia' two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of "atypia, significance uncertain', so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Immunological study of the rectal mucosa of men with and without human immunodeficiency virus infection.

Biopsies of rectal mucosa were taken from 81 men and stained using cytochemical methods for B and T lymphocytes, T cell subsets, immunoglobulin containing plasma cells and mucosal mast cells. The patients studied included human immunodeficiency virus (HIV) infected and non-infected heterosexual and homosexual men, and homosexual men with rectal gonorrhoea. There were increased numbers of T lymphocytes in the lamina propria of the rectum in HIV infected individuals regardless of whether the infection had been acquired through anal intercourse or intravenous drug use. This increase resulted from a marked increase in the numbers of CD8+ suppressor T cells, there also being a reduction in the numbers of CD4+ helper T cells. In non-HIV infected men with rectal gonorrhoea there were increased numbers of CD8+ T cells but no significant difference in numbers of CD4+ cells. No difference was seen in numbers of CD4+ cells. No difference was seen in numbers of immunoglobulin containing plasma cells or mucosal mast cells between HIV infected and non-infected men.

A histological and immunocytochemical study of lymphoid tissue in rectal biopsies from homosexual men.

A histological study of the lymphoid tissue of the rectums of 323 homosexual and 30 heterosexual men (including five intravenous drug users seropositive for human immunodeficiency virus, HIV) was undertaken. Marked lymphoid hyperplasia (germinal centre greater than 680 microns in diameter) was found in 13 men, nine of whom had a sexually transmitted infection of the rectum. Immunocytochemical studies showed that the germinal centres contained B-cells and follicular dendritic cells, surrounded by CD4+ and CD8+ T-cells in a ratio of between 5:1 and 10:1. In HIV-infected men there were decreased numbers of CD4+ cells and increased numbers of CD8+ cells, resulting in a ratio of between 0.8:1 and 2:1. In biopsies from four of seven HIV-infected men the follicular dendritic cell processes appeared shorter and fragmented. The pathogenesis of HIV infection is discussed in the light of these findings.

Prevalence and "incidence" of celiac disease in Edinburgh and the Lothian region of Scotland.

After review of hospital records and jejunal biopsy sections, 703 cases of celiac disease, including 74 cases with dermatitis herpetiformis, were identified in Edinburgh and the Lothian region up to December 31, 1979. Of these, 469 were resident in Lothian, resulting in an overall prevalence of 50/100,000 in men and 74/100,000 in women. The prevalence in men showed no significant variation with age, whereas in women age-specific prevalence varied markedly, with a peak of 126/100,000 at ages 35-44 yr and a low of 28/100,000 at ages 45-54 yr. This variation could not readily be explained, although reduced case ascertainment among women born between 1925 and 1934 could be the basis of a modest cohort effect. There was no evidence that migration or increased mortality at particular ages might be alternative explanations. In children the incidence of celiac disease, as measured by cumulative prevalence with age, increased more than twofold between 1960 and 1975, but since 1976 it has fallen sharply. The fall in incidence in children and the unexplained variations in prevalence in women provide epidemiologic evidence for the role of environmental factors other than gluten ingestion in the etiology of celiac disease.

Free perforation in Crohn's colitis. A ten-year review.

A review of 198 patients with Crohn's disease of the colon who presented over a ten-year period identified six patients with free perforation of the colon (3 percent). Five were females and all were known to have pre-existing Crohn's disease. Four were taking oral corticosteroids at the time of perforation. The sole male presented with acute toxic dilatation of the colon and had not received previous steroids. Pneumoperitoneum was seen in five of the six patients. Subtotal colectomy with ileostomy appears to be the optimum treatment in patients presenting with this complication of Crohn's disease.

Amoebiasis in homosexual men.

The clinical, histopathological, and serological features of 35 homosexual men with infection with Entamoeba histolytica were studied and compared with a group of 35 non-infected homosexual men. Each isolate was of Zymodeme type I. Although there was no significant difference in the numbers of infected and non-infected men with gastrointestinal symptoms (48.6% and 28.6% respectively), the mean duration of symptoms was greater in with amoebiasis (p less than 0.05). The histology of the rectal mucosa was abnormal in 17 (63.0%) of the 27 men with amoebic infection only and in two (7.4%) of the 27 control subjects (p less than 0.001). Serum antibodies reactive with E. histolytica were not shown in any patient.

Dermatitis herpetiformis: diagnosis, diet and demography.

We describe a long term study of 76 patients with dermatitis herpetiformis. Unlike patients with coeliac disease, where the peak incidence was during the first and fourth decades, no dermatitis herpetiformis patients presented in the first decade; also, there was a male preponderance in dermatitis herpetiformis which contrasts with the excess of females in coeliac disease. The apparent prevalence of dermatitis herpetiformis was 11 per 100 000 in our population; approximately one fifth of that of coeliac disease. Jejunal villous atrophy was present in 78% of our dermatitis herpetiformis patients, and a single jejunal biopsy was as effective at detecting this as the multiple biopsy technique. A majority of patients were able to stop, or radically reduce their dapsone or sulphapyridine treatment after the institution of a gluten free diet. Spontaneous remission of the skin lesion occurred in only two patients not receiving a gluten free diet. Gastric parietal or thyroid antibodies were detected in 38% of patients, and three cases of thyroid disease and two cases of pernicious anaemia were detected. Lymphoma developed in two patients, one being intestinal in origin. We conclude that a gluten free diet is of therapeutic benefit in dermatitis herpetiformis and that spontaneous remission is uncommon in those not on a diet. Despite patchiness of the enteropathy, a single jejunal biopsy is quite adequate to diagnose the presence of upper intestinal villous atrophy.

Proctitis in homosexual men. A diagnostic problem.

One hundred and seventy six men with histories of anal intercourse were studied to determine if there was a correlation between the clinical features, cytological findings in the mucosal secretions, and the histological appearance of the rectal mucosa. The presence or absence of gastrointestinal symptoms did not differentiate between patients with and without proctitis. Sigmoidoscopy was normal in each of the 117 men with normal rectal histology. Macroscopic abnormalities were evident in the mucosa of nine of 11 men with infective proctitis, and sigmoidoscopy was normal in 40 of the 48 men with chronic proctitis. Cytological examination was often useful in detecting infective proctitis but not chronic proctitis.

Clinical spectrum of "solitary ulcer" of the rectum.

A review of 40 patients with "solitary ulcer" of the rectum confirmed by rectal biopsy has provided information about the natural history of this unusual condition. At presentation, symptoms usually were the passage of blood and mucus per rectum, alteration in bowel habits, and anorectal pain. Solitary or multiple ulcers were found within 13 cm of the anal margin in 27 patients and were usually sited anteriorly; in 13 patients macroscopic ulceration was absent, though the histopathology of the rectal biopsy specimens was otherwise similar. Rectal mucosal prolapse was found in 25 of 29 patients examined specifically for this. Thirty-one patients were followed-up for a mean period of 4.8 yr (range 1-15 yr). In 22 patients, rectal ulceration was observed at presentation. In 14 of these patients, ulceration persisted despite treatment. In 9 patients presenting without macroscopic ulceration, rectal ulcers were not observed during follow-up; thus two patient groups were apparent. Neither medical nor local surgical treatment consistently achieved relief of symptoms or healing of the lesion.