Morphometry and stereology were used to assess the cytological and architectural characteristics of regenerative and dysplastic colorectal mucosal abnormalities in ulcerative colitis. Reproducibility of measurements was assessed and found to be good, confirming the objective and reproducible nature of morphometric analysis. Discriminant analysis between the morphometric features of regenerative mucosal change and low-grade dysplasia revealed the significant cytological and architectural variables from which a cytological and architectural score were derived. The architectural score was capable of classifying all of the cases into their correct diagnostic category, although a combination of the two scores provided better separation of cases. Probability density analysis was carried out so that probabilities of group membership could be allocated to cases, given their cytological and architectural scores. Discriminant analysis was also applied to low- and high-grade dysplasia. Important cytological and architectural variables were identified and used separately to derive scoring systems. In combination, the dual scoring of lesions was capable of separating low- from high-grade dysplasia, although overlap was still evident. Again, probability density analysis allowed the allocation of cases into one or other category, although a closer examination showed that such a rule could not successfully classify a new set of low- and high-grade dysplasia cases. Quantitative histological analysis of mucosal abnormalities is shown to be of use in the objective diagnosis of reactive and dysplastic change in patients with ulcerative colitis. The use of simple scoring systems and probability based allocation of cases promotes the future role of morphometric techniques in the diagnostic laboratory.

Bayes Theorem↗

PubMed1989

Pathological changes after intravenous streptokinase treatment in eight patients with acute myocardial infarction.

At necropsy five of eight patients (mean age 57 years) who died after intravenous streptokinase treatment for severe acute myocardial infarction (mean Peel index = 18) were found to have a patent infarct related coronary artery. Coronary artery stenoses were caused by fibrofatty atheromatous plaques; there were no residual thrombi in the lumen or acute intimal lesions. Three of these infarcts were of partial thickness (less than two thirds wall width) with sparing of the outer third of the myocardium and subendocardial zones. In the other three patients the infarct related coronary arteries remained histologically closed with residual lumen thrombi and underlying intimal lesions. Two infarcts were transmural. Six of the eight infarcts were noticeably haemorrhagic. Myocardial haemorrhage was confined to areas of necrotic myocardium and did not affect viable regions. These findings suggest that thrombus overlying a complex lesion may be more difficult to lyse than thrombus overlying a simple fibrofatty plaque. They also suggest that myocardial haemorrhage outside the infarct area, which might lead to cardiac rupture or delayed healing, does not usually occur.

Acute Disease↗

PubMed1988

Fatal cardiac failure due to myocardial microthrombi in systemic lupus erythematosus.

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Adult↗

PubMed1988

Architectural morphometry in ulcerative colitis with dysplasia.

Semi-automatic image analysis was used to assess the architectural features of normal colorectal mucosa and ulcerative colitis with and without dysplasia. Eight measured and derived morphometric variables were compared with the histological grading. The main data-set variation was due to: (1) the area of mucosa and epithelium per unit length of muscularis mucosae; (2) mean mucosal and epithelial height; and (3) the percentage epithelium and number of crypts per unit length of muscularis mucosae. Discriminant analysis using the variables mean epithelial height and mean lamina propria area per unit length of muscularis mucosae separated normals (n = 10) from high-grade dysplasia (8). The classification rule allocated low-grade dysplasia (8) to the high-grade category and 60% of regeneration cases (10) to the normal mucosa group. Scatter plots of the two discriminating variables separated normal and regenerative mucosa from dysplasia. Histological review of overlapping cases allowed redesignation of a high-grade dysplasia lesion as low grade. Architectural morphometry may be of use in assessing premalignant mucosal changes in ulcerative colitis as a guide to patient surveillance and therapy.

Colitis, Ulcerative↗

PubMed1988

High iron diamine-alcian blue mucin profiles in benign, premalignant and malignant colorectal disease.

The presence of mucosal hyperplasia and sialomucin goblet cell secretion (transitional mucosa) was assessed in various benign, premalignant and malignant colorectal tissues. Transitional mucosa was seen in diverticular disease, solitary ulcer syndrome of the rectum, ischaemic and irradiation colitis and other diseases including pneumatosis coli, endometriosis, haemorrhoids and a colostomy margin. Adenocarcinomas had a sulphomucin or mixed secretion pattern with transitional features in the adjacent mucosa mucosa (18/27). Premalignant adenomatous polyps showed mixed secretion with transitional glands incorporated in the stalk and sometimes in the adjacent mucosa. Epithelium showing dysplasia secreted sulphomucins and in amounts related to its degree of differentiation. Transitional mucosa may not be a primary premalignant phenomemon. The conclusion and unifying concept is that it is a secondary event related to goblet cell immaturity. This can occur, secondary to proliferation in mucosal inflammation, ischaemia and prolapse or as a phenotypic expression of growth derived from underlying dysplastic epithelium.

Colonic Diseases↗

PubMed1988

Mucin profiles in ulcerative colitis with dysplasia and carcinoma.

Mucin secretion was assessed in Crohn's colitis, in ulcerative colitis with regeneration, dysplasia and carcinoma and in non-colitic adenocarcinoma. The high iron diamine-alcian blue (HID-AB) and periodate borohydride-saponification periodic acid Schiff (PB-KOH-PAS) techniques were used to demonstrate sulphomucins and sialomucins, and O-acylated sialomucins respectively. There was mucosal hyperplasia and increased sialomucin secretion in Crohn's disease, quiescent and active ulcerative colitis. In colitis with carcinoma inflamed mucosa away from the tumour had increased sialomucins as had colitis with dysplasia. They did not differ statistically from each other or from colitic controls without cancer. Dysplastic crypts frequently secreted sulphomucins and the increased sialomucins were in transitional-like glands in the surface fronds or adjacent to the dysplasia. A comparative study of the HID-AB technique gave total correct qualitative allocation of individual quantitatively assessed crypts. Routine HID-AB staining did not aid the recognition of dysplasia in ulcerative colitis. With the PB-KOH-PAS technique colorectal adenocarcinoma showed a significant diminution in O-acylated sialomucins compared with its adjacent mucosa. Mucosal dysplasia in ulcerative colitis displayed a similar trend in O-acylated sialic acid variants, differing with respect to age-and sex-matched colitic controls. The PB-KOH-PAS technique may be of help in assessing mucin secretion in ulcerative colitis as a guide to the evolution of malignancy.

Adenocarcinoma↗

PubMed1988

A morphometric assessment of transitional mucosa in the colon.

Quantitative morphometric analysis was used in 10 resection specimens to assess so-called transitional mucosa immediately adjacent to colorectal carcinoma. Eleven nuclear and cellular variables were measured from the malignant epithelial area and from zones of increasing distance (1 cm) from the lesion. In addition, mean mucosal height was assessed for each zone. Morphometrical differences between the mucosa immediately adjacent to the malignant epithelium and that taken at some distance from it were determined by Mann-Whitney U tests. Transitional mucosa showed increased mucosal height but no nuclear differences from normal mucosa. Other work has shown that there are nuclear morphometric differences associated with premalignant conditions in the colon. Thus, the suggestion that transitional mucosa represents early neoplastic change cannot be supported.

Adult↗

PubMed1987

Classification of normal colorectal mucosa and adenocarcinoma by morphometry.

Semi-automatic image analysis was used to make a morphometrical assessment of 15 nuclear and cellular variables in normal (n = 20) and malignant (n = 30) colorectal epithelium. Principal components analysis on the matrix of correlations between variables identified four main sources of variation within the dataset. These were, in decreasing order of importance: (1) nuclear size, nuclear cytoplasmic ratio and nuclear position within the cell; (2) the variability of nuclear size; (3) nuclear elongation and polarity; (4) nuclear shape and its variation. Discriminant analysis was conducted between histologically normal mucosa (n = 10) and adenocarcinoma in ulcerative colitis (n = 20). Using stepwise variable selection, the mean nuclear cytoplasmic ratio (normal, mean 20.4 (s.d. +/- 2.0); tumour, mean 39.7 (s.d. +/- 7.0)) and the coefficient of variation of nucleus to cell apex distance (normal, mean 19.2 (s.d. +/- 7.5); tumour, mean 47.8 (s.d. +/- 9.1)) were chosen as discriminating features. They were used to derive a discriminant function which gave perfect discrimination between the two groups. Scatter plots of these two variables confirmed complete separation of normal mucosa from adenocarcinoma and provided a simple method of applying the discriminant function. Discriminatory performance did not deteriorate when the function was applied to further normals (n = 10) and adenocarcinoma (n = 10). This study highlights the descriptive differences between normal and malignant colorectal epithelium and shows that case allocation may be made to these two lesion categories using a morphometrically-derived classification rule.

Adenocarcinoma↗

PubMed1987

Morphometrical analysis in ulcerative colitis with dysplasia and carcinoma.

Semi-automatic image analysis was used to assess the epithelium in ulcerative colitis with dysplasia and carcinoma. There were three main sources of variation within the dataset: (1) nuclear size, nuclear cytoplasmic ratio and nuclear stratification; (2) the variation of nuclear size; and (3) nuclear shape and polarity. Discriminant analysis chose the mean nuclear cytoplasmic ratio % and the coefficient of variation of nucleus to cell apex distance to derive a scoring system which completely separated normal mucosa (n = 20) and carcinoma (n = 30). The classification rule allocated all high grade dysplasia to the tumour category. Scores for regeneration and low grade dysplasia overlapped with each other and the normal and tumour groups. Scatter plots of the two discriminating variables showed good separation of regeneration and high grade dysplasia, and a degree of overlap with low grade dysplasia. The scatter plots allowed identification of overlapping and misallocated cases, requiring review of their histology and redesignation of the diagnosis in five cases. This study confirms quantitatively the visual criteria used in grading mucosal changes and their trend from regeneration through dysplasia to carcinoma. It underlines the necessity of assessing not only cytological but also architectural and inflammatory components when diagnosing regeneration and low grade dysplasia. Mucosal morphometry may be of use in confirming high grade dysplasia which is an indication for colectomy.

Adenocarcinoma↗

PubMed1987

Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene p21 product and carbohydrate determinant antigen 19-9.

Two monoclonal antibodies were applied to benign, dysplastic, and malignant human colorectal tissues using immunohistochemical techniques on formalin fixed paraffin embedded material. RAP-5 antibody is directed against a synthetic peptide, reflecting an amino acid sequence of the ras oncogene p21 protein product. Despite using several different techniques and antibody dilutions differential staining between the various epithelial populations was not obtained. RAP-5 also showed other tissue components such as plasma cells, histiocytes, fibroblasts, smooth muscle and vascular endothelium. CA19-9 antibody recognizes an epithelial surface carbohydrate antigen originally derived from a human colorectal carcinoma cell line: it did not stain normal colorectal mucosa or adenomatous polyps, but showed focal expression of variable strength in regenerative, dysplastic, and cancerous mucosa in ulcerative colitis, and in non-colitic colorectal carcinoma. Neither antibody was found to be a reliable marker of the evolution of malignant mucosal changes, although CA19-9 may be of limited use in confirming adenocarcinoma of gastrointestinal origin.

Antibodies, Monoclonal↗

PubMed1987

Pathology of the heart and conduction system in lymphoma and leukaemia.

The clinical and pathological findings in two patients with non-Hodgkin's lymphoma and two patients with T helper cell prolymphocytic leukaemia affecting the heart are described. All four patients had extensive malignant disease, with infiltration of multiple organs. Cardiac infiltration varied from microscopic foci in one case, to grossly identifiable tumour deposits destroying and replacing normal heart structures in three cases. Two patients with infiltration of the conduction system had abnormal electrocardiograms and cardiac dysfunction: one died suddenly, and the other died in heart failure. A third patient with widespread cardiac lymphoma did not show any electrocardiographic abnormalities or dysfunction. Clinicians should be aware of the possibility of cardiac and conduction system disease, particularly in the light of the evolution of specific antitumour chemotherapeutic agents.

Aged↗

PubMed1986

Carcinoma in Crohn's disease of the colon.

Two cases of carcinoma in Crohn's disease of the colon are reported. One patient was a 30-year-old man who had asymptomatic Crohn's ileocolitis resulting in an acute presentation due to toxic dilatation of the colon. This was preceded by a short prodromal period of four weeks, characterized by intermittent diarrhea on the basis of a coloileal tumor fistula. A mucus-secreting adenocarcinoma was present in the sigmoid colon associated with both adjacent and one nearby focus of high-grade mucosal dysplasia. Pelvic wall and abdominal metastases were present, and the patient died two months later. The other patient was a 60-year-old woman who had a nine-year history of biopsy-proven Crohn's proctocolitis. A stricture of the sigmoid colon due to Crohn's disease also harbored an invasive adenocarcinoma. The carcinoma was not evident preoperatively or on initial gross pathologic examination. The presentation and pathology of large intestinal carcinoma in Crohn's colitis are discussed and illustrated.

Adenocarcinoma↗