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PURPOSE: The aim of this study was to re-evaluate the clinicopathologic features of flat adenomas with special reference to the role of central depression found in flat adenomas. METHODS: Clinicopathologic features, such as grade of atypia by size, site, central depression, coexisting lesions, gender, and family history of cancer, were evaluated in 236 flat adenomas from 183 patients selected retrospectively and prospectively. RESULTS: Of the 236 flat adenomas. 175 had mild, 33 had moderate, and 28 had severe (i.e., intramucosal carcinoma) atypia. The frequency of severe atypia correlated positively with size. Severe atypia were significantly more frequent in females (21 percent in females and 10 percent in males; P < 0.05). Sixteen percent of flat adenomas in patients with coexisting cancer showed severe atypia, which was significantly more than those without coexisting cancer (P < 0.05). The frequency of multiple flat adenomas in patients with two or more family members with cancer was 53 percent, which was significantly higher than in patients with one or no family members with cancer (P < 0.05). Central depression was observed in 19 percent of flat adenomas. The rate of severe atypia (22 percent) of flat adenomas with central depression was significantly higher than that (9 percent) of flat adenoma without central depression (P < 0.05). Patients who had flat adenomas with central depression had a higher incidence of coexisting cancer and cancer in the family (P < 0.05 and P < 0.01). CONCLUSION: At colonoscopic examination consideration should be given for the increased potential to become malignant in flat adenomas, especially those with central depression and in patients with a history of malignancy or with a family history of malignancy. [ABSTRACT FROM AUTHOR]

In view of the changing concept of colorectal carcinogenesis during the last 20 years, a historical review of colorectal carcinogenesis is presented.The changing concept of colorectal carcinogenesis was presented in four different periods: 1) carcinogenesis based on surgical materials; 2) carcinogenesis based on polypectomy materials; 3) carcinogenesis based on nonpolypoid neoplasms; 4) carcinogenesis based on molecular biology.In the first period, large adenomas were thought to play the most important role as precursors to colorectal carcinomas; however, in the second period, smaller and nonpedunculated adenomas were found to have a much higher malignancy potential than previously thought. The discovery of nonpolypoid neoplasms, including flat and depressed adenomas/carcinomas, shed light on the new precursor of colorectal carcinomas that were not recognized in the past. Molecular biology clarified a lack of K -ras mutation in nonpolypoid, particularly depressed, neoplasms, suggesting the presence of a novel pathway of colorectal carcinogenesis, different from that in polypoid neoplasms.The concept referred to as the “adenoma-carcinoma sequence” changed because colonoscopic polypectomy specimens were studied, and rather small, nonpedunculated adenomas were found to play an important role as precursors of colorectal carcinomas. The discovery of nonpolypoid neoplasms provides us with new precursors of colorectal carcinomas. The genetic alterations in nonpolypoid neoplasms seem to differ from those in polypoid neoplasms, and genetic alterations in so-called de novo carcinomas need to be clarified [ABSTRACT FROM AUTHOR]

We analyzed the results of a long-term follow-up surveillance of patients with colorectal polyps after endoscopic polypectomy in terms of the cumulative incidence of subsequent colorectal cancer and the clinicopathologic characteristics of carcinomas detected by colonoscopy.The study cohort consisted of 6,715 patients who had received endoscopic resection of single or multiple colorectal polyps and then underwent periodic colonoscopy (or a combination of sigmoidoscopy and barium x-ray examination in some cases) during an average follow-up of six years (40,622 person-years in total).During the follow-up, 31 cases of colorectal cancer containing 15 submucosal invasive carcinomas (T1,N0,M0) and 16 advanced carcinomas were detected. The cumulative incidence of colorectal cancer was analyzed for four subgroups of the 6,715 patients classified according to the diameter, grade of dysplasia, and histologic features of polyps. Furthermore, the depth of invasion, macroscopic configuration of submucosal invasive cancer, and site of colorectal cancer observed in the 31 cases were compared with those of a reference group of 1,497 patients with colorectal cancer treated at Takano Hospital during the same period. Submucosal invasive cancer was the most common type among the colorectal carcinomas detected during follow-up. In terms of macroscopic configuration of submucosal cancer, the superficial type was significantly more common than the protruded type. The superficial submucosal cancer showed a significantly longer interval to detection than the protruded submucosal cancer. By site of lesion, proximal colon cancer was significantly more common.Follow-up colonoscopy appears to be useful in patients with larger polyps (>5 mm). Patients with severe dysplasia and those with malignant polyps should be followed-up carefully. Because submucosal cancer detected by follow-up examination after polypectomy showed higher rates of superficial-type cancer and proximal colon cancer, careful endoscopic examination of the entire colon is important. [ABSTRACT FROM AUTHOR]

To clarify the relation between tumor-suppressor gene p53 expression and histologic grades of dysplasia in colorectal adenomas, we performed immunohistochemical analysis in a series of 59 colorectal polyps and 40 advanced carcinomas.Adenomatous polyps were stained by hematoxylin and eosin and classified into mild, moderate, and severe dysplasia (intramucosal carcinoma), according to the World Health Organization's classification.p53 was positive in 7.1 percent (2/28) of mild, 29.4 percent (5/17) of moderate, and 62.5 percent (5/8) of severe dysplasia. In submucosal and advanced carcinomas, positivity rates were 75 percent (3/4) and 47.5 percent (19/40), respectively. Different staining patterns were found, according to grades of dysplasia. In the adenomas with mild or moderate dysplasia, a few focal crypts showed localized p53-positive staining. Adenomas with severe dysplasia had two different staining types. One was a focal staining type as shown in mild or moderate dysplasia; the other was a diffuse staining type, in which glands with mild or moderate dysplasia, surrounding severe dysplasia area, were also stained. Submucosal and advanced carcinomas showed a strong positive staining in cancer cells only.Overexpression of p53 protein in adenomas with mild or moderate dysplasia and existence of two types of expression in adenomas with severe dysplasia were observed. These facts suggested the possible existence of different pathways in the adenoma to carcinoma progression. [ABSTRACT FROM AUTHOR]

One hundred twenty-eight small flat adenomas (SFAs) were collected from 101 patients, and the clinicopathologic features were investigated. There were 91 adenomas with mild atypia, 20 with moderate atypia, and 17 with severe atypia. SFAs were found more often in males than in females, with a ratio of 3.4:1, and the malignancy rate in females (31.8 percent) was higher than in males (9.3 percent). About 38 percent of the patients had a history of colorectal carcinoma, and 65 percent had a history of colorectal neoplasms. Of 37 patients whose family history was traced, 21 had cancer families. SFAs were prone to be found in patients with a history of colorectal neoplasms and a cancer family. Malignancy rate increased with increasing size. The overall malignancy rate was 13.3 percent, which was considerably higher than that of ordinary small polypoid adenomas (2.8 percent). SFAs were situated more proximally (30.9 percent) than ordinary adenomas; however, there was no relationship between site and malignancy. All the lesions showed tubular adenomas, and there was no villous feature. A central depression was noted in 20 lesions, more frequently in adenomas with higher atypia. All but one adenoma with severe atypia showed a component of lower atypia, supporting the adenoma-carcinoma sequence. [ABSTRACT FROM AUTHOR]

Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the “adenomacarcinoma sequence. [ABSTRACT FROM AUTHOR]

Seventy-five colorectal carcinoma patients (100 separate cancers) with verified cancer family syndrome were re-examined for the evaluation of histologic characteristics in carcinomas and adenomatous polyps in this inherited syndrome in a comparison with control patients with colorectal carcinoma but no hereditary background. In the cancer family syndrome group there were significantly more mucinous carcinomas (35 to 39 percent vs. 20 percent;P<0.05-0.01), and also more poorly differentiated tumors (24 vs. 12 percent) than in the control group. The differences could not be explained by the site or stage of the tumors or by the age or sex of the patients. Additional adenomas occurred quite often both in cancer family syndrome patients (19 percent) and in the controls (16 percent). In the cancer family syndrome group, however, there were more adenomas with moderate or severe dysplasia (P<0.01) and more adenomas with villous features (P<0.05) than in the control group. Mucinous histologic features in colorectal carcinoma, although not fully specific, might be characteristic of cancer family syndrome, and thus serve as one sign in the indentification of the syndrome. The presence of the adenoma-carcinoma sequence in cancer family syndrome also was supported, and the histologic aggressivity of the associated adenomas might signify an accelerated advancement of this phenomenon in cancer family syndrome. [ABSTRACT FROM AUTHOR]

Thirty-three small “flat adenomas,” not more than 1 cm in diameter, were collected from surgically and colonoscopically removed specimens, and their colonoscopic and histologic characteristics were described. There were 14 adenomas with mild atypia, five with moderate atypia, 14 with severe atypia (or focal carcinoma limited to the mucosa). The grade of atypia seems to increase with the size of lesions, and these lesions were assumed to play an important role in the adenoma-carcinoma sequence. The importance of recognizing the presence of these small “flat adenomas” in everyday practice is stressed. [ABSTRACT FROM AUTHOR]