Mixed colorectal polyps. An immunohistologic and mucin-histochemical study

The morphology of mixed colorectal polyps was analysed. Thirteen such polyps were found out of 2700 colorectal polyps (0.5%). Histology showed a spectrum of hyperplastic crypts from almost pure goblet cell population (two polyps) to hypermature serrated epithelium with scanty goblet cells (seven polyps). Tubular adenomas occurred in 12 polyps, and a tubulovillous adenoma was found in the largest polyp. Moderate dysplasia was seen in the five large polyps. The border between neoplastic and hyperplastic cells was usually sharp. Mucin histochemistry showed similarities between the mixed polyps and colorectal carcinomas--namely, the reduction/absence of sialomucin in both mature hyperplastic crypts and adenomatous glands. The expression of carcinoembryonic antigen within the hyperplastic crypts and within the neoplastic crypts showing moderate dysplasia was similar to that seen in colorectal carcinomas, whereas it was normal within the neoplastic crypts with low-grade dysplasia. IgA was reduced or absent in both components. Blood group antigen was found only within the adenomatous component of the largest polyp showing also moderate dysplasia.     

Top-down morphogenesis of colorectal tumors

One of the fundamental tenets of oncology is that tumors arise from stem cells. In the colon, stem cells are thought to reside at the base of crypts. In the early stages of tumorigenesis, however, dysplastic cells are routinely found at the luminal surface of the crypts whereas the cells at the bases of these same crypts appear morphologically normal. To understand this discrepancy, we evaluated the molecular characteristics of cells isolated from the bases and orifices of the same crypts in small colorectal adenomas. We found that the dysplastic cells at the tops of the crypts often exhibited genetic alterations of adenomatous polyposis coli (APC) and neoplasia-associated patterns of gene expression. In contrast, cells located at the base of these same crypts did not contain such alterations and were not clonally related to the contiguous transformed cells above them. These results imply that development of adenomatous polyps proceeds through a top-down mechanism. Genetically altered cells in the superficial portions of the mucosae spread laterally and downward to form new crypts that first connect to preexisting normal crypts and eventually replace them.     

Crypt alterations and collagen deposition in hyperplastic polyps of colorectum

In order to investigate the nature of hyperplastic polyps in the colorectum, 44 longitudinally sectioned crypts from biopsied polyps were analyzed morphometrically and compared with 81 control crypts. Although the crypts in hyperplastic polyps were longer and wider, containing more cells, their cell density was less, particularly in the serrated epithelium. In these crypts, both the tall and short epithelial cells contained cytoplasmic vacuoles, even in the surface epithelium. These cells exhibited increased expression of carcinoembryonic antigen. The subepithelial collagen table was of similar thickness in the polyp and control colonic mucosa, but it extended down along the cryptal wall to a greater depth in the polyp. These and other data indicate an aberrant differentiation of cryptal epithelial cells in the polyp. On upward migration to the surface, these cells appeared to undergo an arrested maturational process. Hence, the hyperplastic polyp may be considered a disease of epithelial cell differentiation.     

Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission.

BACKGROUND: The histogenesis of human colorectal hyperplastic polyps and colorectal adenomas is poorly understood even now. METHOD: Human colorectal adenomas, hyperplastic polyps, and normal colorectal mucosae (patients with familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma were excluded) were obtained during colonoscopy and microdissected into individual crypts. Morphology, cell proliferation characteristics, and fission indices of crypts isolated from these lesions were then studied. RESULTS: Crypts isolated from colorectal adenomas and colorectal hyperplastic polyps were significantly larger (p<0.001) than crypts from normal colorectal mucosae. Crypt fission was an uncommon event in normal colonic mucosae but common in crypts isolated from adenomas and hyperplastic polyps (p<0.001). Analysis of the distribution of mitoses suggested an upward expansion of the proliferation compartment in adenomas to the surface of the crypt with no reversal of proliferating cell distribution, as has previously been described. CONCLUSIONS: Sporadic human colorectal adenomas and hyperplastic polyps grow by the process of crypt fission. Expansion of the proliferative compartment was demonstrated in crypts from adenomas, consistent with deregulation of cell cycle control.     

Comparative electron-microscopic features of normal, hyperplastic, and adenomatous human colonic epithelium. II. Variations in surface architecture found by scanning electron microscopy.

We have used the high resolution and the great depth of focus possible with the scanning electron microscope to define the surface features of normal human colon and human colonic polyps. This technique demonstrates that the surface of the normal colon has a territorialization which encompasses multiple crypts. The surface of the normal colon is covered with both absorptive cells and goblet cells. Hyperplastic polyps are covered with overdeveloped absorptive cells and the normal teritorialization is present but is distorted. Adenomatous polyps are covered with immature cells and, except for the villous adenomas, goblet cells are strikingly absent from the surface. The territorial patterns are totally obliterated in the adenomas.     

Cellular localization of cyclo-oxygenase isozymes in Crohn’s disease and colorectal cancer

Deregulation of cyclo-oxygenase isozyme expression has been shown to be a consistent feature of inflammatory bowel diseases and colorectal cancer in humans. This study investigated the cellular localization of aberrant cyclo-oxygenase expression in normal and diseased colon. Biopsies of seven normal colonic tissues, eight tissue samples from patients suffering from Crohn’s disease, five polyps from patients with familiar adenomatous polyposis coli, and ten sporadic adenocarcinomas were analyzed using isozyme-selective immunoprecipitation, western blotting, and immunohistochemistry. Cyclo-oxygenase-1 expression was demonstrated in normal human colon, Crohn’s disease, and colorectal tumors. In normal colon and also in adenomatous polyps, cyclo-oxygenase-1 specific immunosignals were localized to epithelial cells of the upper part of the crypts and endocrine cells of the lower part. In Crohn’s disease cyclo-oxygenase-1 expression was restricted to cells of the inflammatory infiltrate. While barely detectable in normal colon, cyclo-oxygenase-2 protein was strongly increased in epithelial cells located in the uppermost part of the crypts, in surface epithelial cells, and in mononuclear cells of the lamina propria of Crohn’s disease. The constitutive overexpression of cyclo-oxygenase-2 protein observed in the majority of the adenomatous polyps and all adenocarcinomas was attributed to both epithelial and interstitial cells in that the latter predominated in adenomas, and epithelial cells were the prevailing cyclo-oxygenase-2 expressing cell type in adenocarcinomas. In conclusion, both autocrine and paracrine effects of aberrant cyclo-oxygenase-2 expression may contribute to the development of Crohn’s disease and colonic tumor development. Accepted: 7 September 1999     

Is Epidermal Growth Factor Involved in Development of Duodenal Polyps in Familial Polyposis Coli?

Duodenal adenomas are a frequent extracolonic manifestation in patients with familial polyposis coli (FPC). Epidermal growth factor (EGF), a polypeptide that stimulates cellular growth and differentiation, is localized in Paneth cells in the small intestine. In two patients with FPC, we found EGF immunoreactivity in duodenal adenomas. Numerous EGF immunoreactive Paneth cells were localized, not as usually, in the bottom of the crypts, but scattered along the crypts alone or in clusters. We do not know whether EGF is involved in the development of duodenal polyps in FPC patients, or whether the present findings represent secondary changes in duodenal polyps.     

Cell kinetics in the jejunal crypt epithelium in malabsorption syndrome with cow's milk protein intolerance and in coeliac disease of childhood.

Cell kinetics in the proximal jejunal epithelium were studied by the methods of Cairnie et al. and Wright et al. Seventeen children with untreated malabsorption syndrome and cow's milk protein intolerance (CMI) and 12 of these on a cow's milk free diet were compared with 47 children with untreated coeliac disease, with 15 of these on a gluten free diet, and with 15 controls. The total number of cells in the crypts of the patients with CMI was 1.8 times (P less than 0.001) and in patients with coeliac disease 2.4 times (P less than 0.001) that seen in the controls. During the elimination diet the total number of cells in the crypts returned to the level seen in the controls. The mitotic indices, both crude and corrected, were significantly higher (P less than 0.001) in untreated patients with CMI and those with coeliac disease than in the controls. During dietary treatment the indices fell, but not quite to the level of the controls. These small differences between the two groups may be due to the difference in the causative agents or to the different ages of the patients.     

Effects of gastric fundectomy and antrectomy on the colonic mucosa in the hamster.

The effects of gastric fundectomy and antrectomy on the colonic mucosa were studied in hamsters over 5 and 25 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly increased after fundectomy and significantly decreased after antrectomy. Five days after fundectomy, there was a significant increase in scintigraphically determined colonic tissue [3H]-thymidine uptake and [3H]-thymidine labeling index of goblet cells, both of which were reduced 5 days after antrectomy. After fundectomy, the labeling index was maximal in differentiating-proliferative cells in the midportion of the colonic crypts, whereas the labeling index of the immature proliferative cells at the base of the crypts did not differ from that in the controls. On day 25, the crypt size and the number and percentage of goblet cells in the crypts were significantly increased in fundectomized animals. The number and percentage of goblet cells in antrectomized animals were significantly reduced on day 25. It is concluded that fundectomy in the hamster induces colonic mucosal hyperplasia with goblet cell proliferation, whereas antrectomy leads to retardation of colonic goblet cell proliferation.     

Histoclinical Long-standing Follow-up Study of Hyperplastic Polyps of the Stomach

In a series of 2,013 gastric polyps in 1,201 patients, morphological and histopathological studies have been performed. Ninety-three hyperplastic polyps in 56 patients have been followed-up endoscopically and histopathologically for five to 12 years. The incidence of detection of gastric polyps has increased: 1.4% in 1967 to 8.7% in 1979 year by year. Thirty patients (54%) among the 56 showed changes in number, size or shape of polyps during follow-up. Twenty patients (37%) revealed numerical changes (increase in 16 patients, reversion in three patients and vanishing in two patients).
Twenty-eight polyps (30%) showed morphological changes, six of them showed continuous enlargement, 18 lesions repeated enlargement, stationary or reduction stages, three lesions were reversed and two polyps disappeared.
Histopathologically, three lesions showed transformation from the hyperplastic type to adenoma while demonstrating morphological enlargement. Two of these showed increase in cellular atypia, from the hyperplastic type through adenoma with severe atypia and finally to carcinoma in the polypectomy specimens. From this study, it was concluded that although hyperplastic polyps show changes in size, shape or number with passage of time, malignant changes occur in only a few cases.     

Intraepithelial enteroendocrine cells in cecum and appendix from ovoalbumin sensitized rabbits

Intraepithelial enteroendocrine cells (IEC) produce peptides which influence motility, secretion and absorption of nutrients. Recently the role of these cells in the immune mucosal system is under study. The aim of the present study was to evaluate the modifications in number of IEC in cecum and appendix from Ovalbumin (OVA) sensitized rabbits. Twenty adult New Zealand rabbits were separated in two groups: Group 1 (G1 = 10) not sensitized normal control. Group 2 (G2 = 10) were sensitized twice intraperitoneally with 70 mg OVA and 30 mg ALUM/ml (aluminium hydroxide). Anti OVA specific IgE was evaluated by means of PCA test (passive cutaneous anaphylaxis). Samples form cecum and appendix were fixed in buffered formaldehyde 10%, paraffin embedded and stained with anti-Chromogranin A for neuroendocrine cells. 400 high power fields were counted in each animal, referred as IEC/100 enterocytes. In cecum surface epithelium and crypt were considered. Surface epithelium, deep crypts and superficial crypts were evaluated in appendix. Results showed in cecum in G1:1,6 IEC/100 enterocytes in surface epithelium and 3/100 in crypts; G2 6 IEC/100 in surface epithelium and 12/100 in crypts. The difference between G1 and G2 was statistically significant (p < 0.05). In appendix surface epithelium from G1 showed 5.2/100 while G2 5.4/100. Superficial crypts 8.5 (G1) and 11.3 (G2) (p < 0.05) and deep crypts 4.9 (G1) and 8.5 (G2) (p < 0.01). The results showed that OVA-sensitized animals presented increment in the number of IEC in surface epithelium and crypts which may indicate a relationship between these cells and rabbit mucosal immune system.     

Initial kinetic changes of prostaglandin E2-induced hyperplasia of the rat small intestinal epithelium occur in the villous compartments

This study was performed to further identify the sequence of cell kinetics that occurs in the development of gastric and intestinal epithelial hyperplasia after orally administered prostaglandins of the E series. A high-dose, short-treatment schedule was used to examine the initial effects on kinetic parameters in the rat small intestinal epithelium. Groups of rats were killed after a single dose of oral prostaglandin E2 at 1 h after in vivo labeling with [methyl-3H]thymidine and during continued treatment at 6, 12, 24, 48, 72, and 96 h. As evidenced by autoradiography, the earliest change produced by prostaglandin E2 was an increased cellularity of the villous compartment (p less than 0.05 after 24 h). There was no change of labeling index of the villous compartment or of the leading edge of labeled cells within 24 h. At 48 h, the increased cellularity was accompanied by a significantly elevated labeling index of the villi. Throughout the study period no significant differences were observed between groups in the number of cells or labeling indices in the jejunal crypts, or in cellular input from the crypts to the villi. Epithelial turnover time in the placebo and treatment groups was 69 and 71 h, respectively. To exclude the possibility that prostaglandin E2 initially affects cell birth rate and mean cell cycle time, a metaphase blocker was given after 4 days of treatment in a second study. Animals were killed after 0, 0.5, 1.0, 1.5, and 2.5 h. The rate of entry into mitoses was 8.1% cells/h in controls compared with 8.2% cells/h in treated rats. The distribution of mitoses within crypts was identical in the two groups and the mean cell cycle time was 13.6 and 13.2 h, respectively. Also in this study there were trophic changes of the villi. It is concluded that the hyperplasia produced by oral prostaglandin E2 starts in the villi of the small intestine and is initiated by reduced cell exfoliation from the villous tips. Previously recorded retention of cellular elements in villi and crypts, increased cellularity of the proliferative compartments, and reduced mitotic index are secondary events.     

Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer

AIMS: Intracellular folate deficiency has been implicated in colonic carcinogenesis in epidemiological studies and animal and human cancer models. Our aim was to determine the effect of folate supplementation on patients with recurrent adenomatous polyps using rectal mucosal cell proliferation as a biomarker. PATIENTS AND METHODS: Eleven patients with recurrent adenomatous polyps of the colon were randomised into a treatment group (n=6) receiving a dietary supplement of 2 mg folic acid per day for three months and a control group (n=5) receiving a placebo. Rectal biopsies where taken at 10 cm from the anal verge prior to supplementation and repeated at four, 12, and 18 weeks from the start of the supplementation. Each biopsy was immediately incubated in culture medium enriched with bromodeoxyuridine (BrdU). The S phase cells which incorporated BrdU into their DNA were identified following immunohistochemical staining. Twenty five orientated crypts were identified for each time point and the number and position of BrdU positive and BrdU negative cells were counted. BrdU labelling indices (LIs) were calculated for the entire crypt and for each of five equal compartments running consequently from the base to the luminal surface. RESULTS: The LI of the treatment group (9.1 (6.7, 12.3)) and the control group (9.3 (7.8, 10.3)) were comparable at the start. Over the duration of the supplementation period, LI in the control group did not alter significantly (9.3 (7.8, 10.3) v 9.6 (8.9, 10.4)). However, LI of the folate treated group was lowered after 12 weeks of supplementation (9.1 (6.7, 12.3) v 7.4 (5.3, 9.6)). Analysis of the LI for compartments within the crypt showed that the most significant drop in number of proliferating cells was in the upper most regions of the crypt. CONCLUSION: These data indicate that (a) folate supplementation decreases colonic mucosal cell proliferation in a high risk group for colon cancer and (b) the most significant reduction takes place at the luminal aspect of the crypt.     

Expression of the glucocorticoid receptor alpha and beta isoforms in human nasal mucosa and polyp epithelial cells

The lower sensitivity of the inflamed nasal mucosa to glucocorticoids might be related to an increased expression of the glucocorticoid receptor (GR) beta isoform. We investigated GRalpha and GRbeta mRNA expression in epithelial cells from nasal mucosa and nasal polyps. GRalpha mRNA was at least 1000 times more expressed than GRbeta mRNA in both tissues. GRbeta expression (mean+/-SEM of 10(3) cDNA copies/microg of total RNA) was higher in nasal polyps (1.15+/-0.19; n=27; P<0.01) than in nasal mucosa (0.62+/-0.10; n=32). Nasal polyps with > 3% of inflammatory cells had higher GRbeta levels (1.40+/-0.29; n=16) than both nasal mucosa (P<0.01) and polyps with < or = 3% of inflammatory cells (0.80+/-0.18; n=11; P<0.05). No difference in GRbeta expression was found between nasal mucosa and polyps with < or = 3% of inflammatory cells. GRbeta expression correlated with the inflammatory cell number, especially with mast cells (r=0.50, P<0.0001). There was no difference in GRalpha mRNA expression between nasal mucosa and nasal polyps. In summary, GRalpha is far more expressed than GRbeta in both tissues. The increased expression of GRbeta may be related to the presence of inflammatory cells.     

Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer.

The effects of 12 weeks of omega-3 fatty acid supplementation on rectal mucosal proliferation were assessed with [3H]thymidine autoradiography in a double-blind, placebo-controlled study of 20 patients with sporadic adenomatous colorectal polyps. In the group of 10 that received fish oil containing eicosapentaenoic acid (4.1 g/day) and docosahexaenoic acid (3.6 g/day), the mean percentage of replicative "S"-phase cells in the upper part of colonic crypts (considered a reliable marker of colon cancer risk) significantly dropped from the baseline level after only 2 weeks of treatment and remained lower throughout the study period; no change in upper-crypt labeling was observed in the 10 placebo patients. Rectal mucosal eicosapentaenoic acid content increased in fish oil patients, whereas arachidonic acid levels decreased. The fish oil-induced kinetic changes represent contraction of the proliferative compartment to the levels of a low-risk population and may be related to omega-3 fatty acid effects on the arachidonic prostaglandin pathway. In this short-term trial, fish oil appeared to exert a rapid effect that may protect high-risk subjects from colon cancer.     

Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis

PURPOSE: The aim of this study was to establish the prevalence of adenomatous polyps in the ileal pouch of patients with familial adenomatous polyposis. METHOD: Forty-three patients who had an ileal pouch for familial adenomatous polyposis were invited to have a careful endoscopic examination of their pouch, including dye spraying. The number of polyps was recorded, and up to ten were biopsied. In addition, four random biopsy specimens were taken from the proximal and four from the distal pouch. RESULTS: Thirty-three patients with a median age of 36 (range, 14-63) years who had a pouch (5 Kock and 28 pelvic) for a median of 7 (range, 1-19) years accepted the invitation. Twenty-one patients (64 percent) had endoscopically identified polyps, the number of polyps ranging from 1 to 100 (median, 10) and varying in size from 1 to 3 mm. Fourteen patients (42 percent) had adenomatous polyps and 4 of these also had microadenomas on random biopsies. Nine of the 14 patients with adenomas also had lymphoid polyps. Seven patients had lymphoid polyps only and two of these patients had a microadenoma on random biopsy. Four of 12 patients with no visible polyps had microadenomas in their random biopsies. The presence of adenomatous polyps (Pearson's correlation; P < 0.01) increased with the age of the pouch. In total, 20 of 33 (60 percent) patients had adenomas and or microadenomas. CONCLUSION: Adenomatous polyps occur frequently in ileal pouches. These findings are of concern, and therefore, regular surveillance seems warranted until the natural history of these adenomatous polyps is determined.     

[3H]Thymidine-labeled colonic epithelial cells and mucosa in mice and man

Since normal epithelial cell proliferation occurs chiefly in the lower two thirds of colonic crypts, the presence of aberrant DNA-synthesizing cells (tritiated thymidine labeled) at the mouth and on the surface of colonic crypts is being assessed as a predictive indicator of the development of neoplasia in patients at high risk. These would include patients with previous polyps or colon cancer or family history of either or both. Surface cells are obtained by pulsatile saline lavage of the lower bowel and incubated with tritiated thymidine ([³H]TdR) for autoradiographic observation. Findings in each high-risk category are presented and compared with [³H]TdR labeling data from a biopsy taken at the close of the procedure. The lavage technique has also been carried out on mice injected with the colon carcinogen 1,2-dimethylhydrazine (DMH). Mice were demonstrated to have [³H]TdR-labeled cells and cellular atypia while being hemoccult negative and asymptomatic for overt disease. Evaluation of human material preliminarily demonstrated the presence of surface-labeled epithelial cells in a high percentage of patients at risk for colon cancer.     

Solitary Rectal Ulcer Syndrome: A Clinicopathological Study of 13 Cases

Background/Aims:

Solitary rectal ulcer syndrome (SRUS) is a rare disorder that has a wide spectrum of clinical presentation and variable endoscopic findings. To further characterize the clinical and pathological features, a retrospective, hospital-based clinicopathological study was conducted.

Materials and Methods:

All cases of SRUS diagnosed at Farwania Hospital, Kuwait, between 2002 and 2007 were retrieved from the computerized filing system. The histological slides were reviewed by two authors to confirm the diagnosis. Immunohistochemical stain for smooth muscle actin (SMA) was performed. The clinical files were reviewed for clinical features and endoscopic findings.

Results:

Thirteen cases were identified: 8 males and 5 females. The age range was 15–85. Rectal bleeding, constipation, and abdominal pain were the most common presenting symptoms and were seen, either alone or in various combinations, in 12 of the 13 cases. Rectal ulceration was the most common endoscopic finding, being seen in 9 of the 13 cases; 3 of these cases had multiple ulcerations. Two patients had rectal polyps, with one of them having multiple polyps. The histological examination revealed surface serration, fibromuscular obliteration of the lamina propria, and crypts'' distortion in all the cases. Seven of the cases had diamond crypts. Ectatic mucosal vessels were a common finding. Positivity for SMA in the lamina propria was seen in all examined cases.

Conclusion:

SRUS is a rare disorder and only 13 cases were diagnosed in Farwania hospital over a 6-year period. The clinical presentation of our patients was variable. The presence of polyps and multiple ulcerations on endoscopy is further evidence that SRUS is a misnomer. Surface serration, fibromuscular obliteration, and crypts'' distortion are the most characteristic features. The presence of diamond crypts is an additional diagnostic feature.     

Effect of gut-associated lymphoid tissue on cellular proliferation in proximal and distal colon of the rat

In previous studies, chemically induced colonic carcinomas were found to originate preferentially from crypts adjacent to lymphoid tissue. Proliferative parameters and mucosecretion were analyzed in proximal and distal rat colon in relation to the proximity of lymphoid patches. Animals received an intraperitoneal pulse of bromodeoxyuridine 1-hr before death. In both proximal and distal colon, crypts located at the immediate proximity of the lymphoid formations contained fewer mucous cells (P<0.001), but a higher percentage of proliferative epithelial cells (P<0.001) than the crypts far from lymphoid formations. The labeling index was higher in crypts adjacent to lymphoid patches compared to crypts distant from lymphoid patches only in the lower third of the crypts. The association of an increased proliferative activity and a decrease in differentiated mucosecreting cells in colonic crypts adjacent to lymphoid patches could be related to the particular sensitivity of these crypts cells to the effects of mutagens and carcinogens.     

Pathology of colorectal cancer

The earliest phases of colorectal tumourigenesis initiate in the normal mucosa, with a generalised disorder of cell replication, and with the appearance of clusters of enlarged crypts (aberrant crypts) showing proliferative, biochemical and biomolecular abnormalities. The large majority of colorectal malignancies develop from adenomatous polyps. These can be defined as well demarcated masses of epithelial dysplasia, with uncontrolled crypt cell division. An adenoma can be considered malignant when neoplastic cells pass through the muscularis mucosae and infiltrate the submucosa. Definitions like "carcinoma in situ" or "intramucosal carcinoma" should be abandoned, since they lead to confusion. Although several lines of evidence indicate that carcinomas usually originate from pre-existing adenomas, this does not imply that all polyps undergo malignant changes, and does not exclude "de novo" carcinogenesis. Besides adenomas, other types of polypoid lesions include hyperplastic polyps (showing elongated crypts often with cystic dilatation), serrated adenomas (with a serrated glandular pattern], flat adenomas (flat lesions which are difficult to detect in routine lower endoscopy, but may possess malignant potential), hamartomatous polyps (which show a complex branching pattern of smooth muscle supporting normal lamina propria and glands), and inflammatory polyps. Colorectal carcinomas are one of the most frequent neoplasms in Western society; the macroscopic appearance of these lesions may be that of a polypoid vegetating mass or of a flat infiltrating lesion. Most of these tumours are adenocarcinomas (96%), that, in some cases, show a mucinous component. More rare malignancies of the large bowel include signet-ring cell carcinoma, squamous carcinoma, undifferentiated neoplasms and medullary type adenocarcinoma (solid carcinoma with minimal glandular differentiation or slight cellular pleomorphism). Colorectal carcinoma can be graded into well, moderately and poorly differentiated lesions; there is little evidence, however, that grading may be of help in evaluating prognosis of affected patients. In conclusion, colorectal tumours cover a wide range of premalignant and malignant lesions, many of which can easily be removed at endoscopy. It follows that colorectal neoplasms might be prevented by interfering with the various steps of carcinogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas of various dimensions, and eventually evolves into malignancy.