Basil C. Morson

The evolution of cancer of the colon and rectum.

The malignant potential of adenomas of the colon and rectum varies with size, histological type and grade of epithelial atypia. The adenomatous polyp is usually small and has a low malignant potential, whereas tumors with a villous structure are usually larger and have a much higher cancer rate. Severe atypia is more common in villous adenomas than in adenomatous polyps. Evidence is presented which suggests that most cancers of the colon and rectum have evolved through the polyp‐cancer sequence although the majority of adenomas do not become cancerous during a normal adult life span. The slow evolution of the polyp‐cancer sequence is stressed. The implications of the polyp‐cancer sequence for the design of cancer prevention programmes and the study of the aetiology of large bowel cancer are discussed.

Histological typing of intestinal tumours

Introduction Histological Classification of Intestinal Tumours Small Intestine Appendix Large Intestine Anal Canal Anal Margin Definitions and Explanatory Notes Small Intestine Appendix Large Intestine Anal Canal Anal Margin Subject Index

Juvenile polyposis–a precancerous condition

Clinical and pathological findings in 87 patients with juvenile polyposis have been reviewed; 1032 polyps were available from 80 of these patients; 840 were typical spherical juvenile polyps whereas 169 differed in being multilobulated or showing a villous configuration; 79 (46.7%) of the latter contained foci of epithelial dysplasia whereas only 76 (9.0%) of the typical juvenile polyps were dysplastic. The series also included 21 adenomas and two hyperplastic (metaplastic) polyps. The demonstration of dysplasia provides a histogenetic mechanism for the evolution of colorectal cancer from hamartomatous polyps; 18 juvenile polyposis patients have developed colorectal cancer at a mean age of 34 years (range 15–59). The clinical outcome was generally poor. No clinical or pathological distinction could be made between polyposis patients with and without colorectal cancer. Thus, the development of cancer in juvenile polyposis appears to be a random event. A working definition of juvenile polyposis is provided: (1) more than five juvenile polyps of the colorectum; and/or (2) juvenile polyps throughout the gastrointestinal tract; and/or (3) any number of juvenile polyps with a family history of juvenile polyposis. It is suggested that the condition should be treated as seriously as familial adenomatous polyposis except that regular colonoscopic surveillance may obviate the need for prophylactic colectomy.

Pathology of colorectal adenomas: a colonoscopic survey.

The size, histological type, and grade of dysplasia of a large series of colorectal adenomas removed by colonoscopic polypectomy were matched against other variables such as anatomical site, age, sex, and number of adenomas per patients. Special emphasis was placed on the criteria for grading dysplasia in adenomas and the possible significance of severe dysplasia as a selective marker for increased colorectal cancer risk. The results showed that small adenomas (mostly with mild dysplasia) were evenly distributed throughout the colorectum but that adenomas showing severe dysplasia (mostly the larger tumours, greater than 10 mm diameter) were concentrated in the left colon and rectum, particularly the sigmoid part which is also the segment with the highest risk of colorectal carcinoma in high risk populations. Severe dysplasia in adenomas appears to be a selective histopathological marker for increased colorectal cancer risk. It is closely linked with increasing age and numbers of adenomas per patient, with the large adenomas and particularly those with a villous component in their histology. Severe dysplasia and multiple adenomas could be valuable markers for selecting from the total adenoma population those most deserving of close surveillance in follow-up cancer prevention programmes. Conceptually it would appear advantageous to think in term of the dysplasia-carcinoma sequence in the colorectum rather than the polyp-cancer or adenoma-carcinoma sequence. The implications of these results in the study of the aetiology of colorectal cancer are discussed.

Evolution of cancer of the colon and rectum

In this paper the opportunity is taken to describe the personal position of the speaker with respect to the evolution of cancer of the colon and rectum. A general account of the predisposing causes is presented, with emphasis on the malignant potential of adenomatous polyps and villous adenomas. The significance of the polyp–cancer sequence is discussed, and some evidence given about how long it takes for polyps to become cancerous. Some reference is also made to the etiologic significance of the polyp–cancer sequence. Do all cancers of the colon and rectum arise from adenomatous polyps or villous adenomas? An attempt will be made to answer this question and to review the alternatives to this mode of histogenesis.

Some peculiarities in the histology of intestinal polyps

Thejuvenile polyp of the rectum and colon is probably a malformation or hamartoma of the tissues of the intestinal mucosa without the participation of the muscularis mucosae. In particular, the histologic appearance suggests an abnormality of the mucosal connective tissue or lamina propria.ConclusionsThejuvenile polyp of the rectum and colon is probably a malformation or hamartoma of the tissues of the intestinal mucosa without the participation of the muscularis mucosae. In particular, the histologic appearance suggests an abnormality of the mucosal connective tissue or lamina propria.The intestinal polyps of the Peutz-Jeghers syndrome are hamartomatous tumors of the mucous membrane in which there is a malformation of the muscularis mucosae, tree-like in appearance. The epithelial and connective tissue elements of the polyps cover the branching bands of smooth muscle as in normal mucosa, and they are composed essentially of normal cells in their normal relationship to each other.Solitary polyps of the small and large intestines are seen occasionally, which are histologically identical with the Peutz-Jeghers type, but without any clinical evidence of the syndrome. These are also hamartomatous in nature, and should be distinguished from true adenomatous polyps.The histology of certain small mucosal polyps in the rectum and colon has been described. It is suggested that these should be calledmetaplastic polyps. Their nature is unknown, but there is no evidence that they are either hamartomatous or neoplastic. They should not be confused histologically with early adenomatous changes in the intestinal mucosa.

Pseudo-carcinomatous invasion in adenomatous polyps of the colon and rectum.

The histology of pseudo-carcinomatous invasion in adenomatous polyps of the colon and rectum is described and the appearances are contrasted with those seen in malignant polyps. The recognition of pseudo-carcinomatous invasion is important in the differential diagnosis of benign and malignant polyps of the large bowel. Failure to distinguish it from carcinoma may lead to wrong treatment and false reports of the incidence and prognosis of cancer of the colon and rectum. The evidence suggests that pseudo-carcinomatous invasion may be the result of repeated twisting of the stalk of a polyp which causes haemorrhage and this facilitates the passage of non-malignant adenomatous epithelium through the muscularis mucosae.

Primary malignant lymphoma of the large intestine complicating chronic inflammatory bowel disease

Ten cases of malignant lymphoma of the colon and rectum complicating chronic inflammatory bowel disease are presented. Seven patients had chronic ulcerative colitis with a history varying from 6 to 20 years. There was extensive colitis in six of these patients and left‐sided colitis in one. All seven lymphomas showed the pathological and immunohistological features of primary B‐cell tumours of the gastrointestinal tract with a predominance of high‐grade tumours. Three patients had Crohns disease of the large intestine complicated by malignant lymphoma of the sigmoid colon or rectum. The history of Crohns disease varied from 30 months to 20 years and in each case there was fissuring and fistulae. There was extensive anal involvement in two cases. Histologically the three lymphomas were heterogeneous: one was of ‘granulomatous’ T‐cell type and the other two were markedly polymorphic and of equivocal phenotype. They were also characterized by numerous multinucleate tumour giant cells. Primary colorectal malignant lymphoma should be regarded as a rare, but significant, complication of ulcerative colitis. Immunosup‐pression may be an additional factor in the genesis of intestinal lymphoma in Crohns disease. The prognosis appears to be dependent on factors already known to be of prognostic significance in primary gut lymphomas: a predominance of high‐grade tumours suggests that the outlook is generally worse than that for idiopathic primary large intestinal lymphoma.

Malignant lymphoma with eosinophilia of the gastrointestinal tract

Lesions of the gastrointestinal tract with massive tissue eosinophilia may present a difficult diagnostic problem. In a series of 250 gastrointestinal lymphomas drawn from the files of St Bartholomews and St Marks Hospitals there were 28 cases of a lymphoma with distinctive histological features, characterized by a massive tissue eosinophilia. Two of these tumours were present in the stomach and 26 in the small intestine. Eight of the latter were associated with coeliac disease. On low power examination a zoning phenomenon was regularly seen and fissuring ulceration, with perforation and fistula formation, was a common finding. The tumour cells were large and pleomorphic with irregular nuclear morphology and prominent nucleoli. Eosinophils were the predominant inflammatory cell associated with the lymphoma but plasma cells, epithelioid histiocytes and small lymphocytes were also present. Vascular changes were prominent. Involved lymph nodes showed gross expansion of the paracortex by tumour. Immunohistochemical studies showed that this lymphoma was probably of T‐cell origin.

Precancer and cancer in inflammatory bowel disease

&NA; The risk of cancer in inflammatory bowel disease (IBD) is increased although it remains low. A clinical subgroup of patients with extensive or total ulcerative colitis and a history of symptoms for more than 10 yr is at greatest risk. In these patients biopsy evidence of epithelial dysplasia has successfully been used as a marker for increased cancer risk. A classification system for dysplasia has recently been devised, consisting of 3 categories: negative, indefinite and positive for dysplasia. The criteria for each category are discussed. For patients at high risk who decline prophylactic colectomy, a cancer surveillance programme involving periodic clinical assessment, sigmoidoscopy, colonoscopy and rectal and colonic biopsies has provided a reasonable alternative.