Luminal Histological Outline and Colonic Adenoma Phenotypes

Transcription

1 Luminal Histological Outline and Colonic Adenoma Phenotypes CARLOS A. RUBIO Gastrointestinal and Liver Pathology Research Laboratory, Department of Pathology, Karolinska Institute and University Hospital, 17176, Stockholm, Sweden Abstract. Background: The luminal appearance of histological sections from colonic adenomas exhibits two different profiles: one regularly smooth and the other asymmetrically lumpy. These two modalities were compared to the size, the histological phenotype and the degree of epithelial neoplasia. Materials and Methods: For this purpose, the largest section of 107 consecutive endoscopically removed colonic adenomas was digitalized using an Epson Perfection 4990 PHOTO device. Profiles were enhanced with the Adobe Photoshop CS program. Results: Asymmetrically lumpy profiles were found in 96% (22/23) of the sections from adenomas measuring 15 mm, in 72% (39/54) of those having villous, mixed serrated or microtubular configurations and in 89% (24/ 27) showing carcinoma according to the Vienna classification. Conclusion: The asymmetrically lumpy profile of sections from endoscopically excised colonic adenomas correlated with the size of the sections, the histological phenotype and the degree of neoplastic transformation. Studies have been initiated to clinically explore whether the luminal configuration of colonic adenomas can be of help in predicting, before endoscopical removal, accepted histological parameters. Although the first patient with a rectal polyp was recorded in 1721 (1), it took 161 more years to realize that rectal polyps were a risk factor for cancer development in that organ (2). The polyps that carry a risk for cancer development are called adenomas. In 1951, Jackman and Mayo (3) launched the progressive adenoma-carcinoma sequence paradigm, which was immediately accepted. More than 20 years later, Muto et al. (4) found that adenomas of a large size, with a high degree of epithelial dysplasia and having villous configurations were more prone to proceed to invasive carcinoma. On the basis of their structural configurations, colorectal adenomas have more recently been classified into tubular, Correspondence to: C.A. Rubio, MD, Ph.D., Gastrointestinal and Liver Pathology Research Laboratory, Department of Pathology, Karolinska Institute and University Hospital, 17176, Stockholm, Sweden. Fax: , Carlos.Rubio@ki.se Key Words: Adenoma, colon, profile, lumen, Vienna classification. villous, mixed (tubulo-villous), serrated and microtubular (5-7), and, according to the degree of cellular aberration, into those with dysplasia (low-grade or high-grade) or with carcinoma (carcinoma in situ, i.e. intraepithelial carcinoma, intramucosal carcinoma and submucosal carcinoma) (8). Lately, while investigating tissue sections from protruding colorectal adenomas (8), it became apparent that their luminal border could display two different profiles: one regularly smooth and the other asymmetrically lumpy. The aim of the present work was to investigate whether a particular adenoma profile, as seen at the luminal border of tissue sections, had any relationship with size, histological phenotype and/or the degree of epithelial neoplasia. Materials and Methods The study samples comprised 107 consecutive endoscopically removed, formalin-fixed colonic polyps, subsequently reported as adenomas at histological examination. Histological sections were stained with H&E. The largest diameter of the largest H&Estained tissue section was measured with a conventional ruler and digitalized using an Epson Perfection 4990 PHOTO device ( The profile of the sections was improved by boosting the background of the images using the Adobe Photoshop CS program (Adobe Systems Inc, CA, USA). Inverted functions and various filters were applied. Statistics. The non-parametric Wilcoxon test was carried out using StatView Version 4.5 software (Abacus Concepts, Berkley, CA, USA). Differences were considered significant at 95% confidence level (p<0.05). Results Of the 107 adenoma sections, 34 had a regularly smooth luminal profile (Figure 1) and the remaining 73 an asymmetrically lumpy luminal profile (Figure 2). The comparison between these two luminal profiles and the size of the largest section in the 107 adenomas is shown in Table I. It is seen that 96% (22/23) of the adenomas measuring 15 mm corresponded to those having an asymmetrically lumpy profile. Thus, of the adenomas measuring 15 mm, only one (4%) had a regularly smooth luminal profile (p<0.05) /2007 $

2 Figure 1. H&E stained section from a colonic adenoma digitalized in an Epson Perfection 4990 PHOTO device. The background was enhanced by the aid of the Adobe Photoshop CS program to highlight the luminal profile of the adenoma. Section from an adenoma measuring 16 mm in the largest diameter, showing a regularly smooth luminal profile (enlarged from natural size). The two luminal profile modalities were also compared to the histological phenotype of the adenomas (Table II). The Table shows that 72% (39/54) of the adenomas with villous, mixed serrated and microtubular adenomas had an asymmetrically lumpy profile (p<0.05). The remaining 28% (15/54) of the adenomas with villous, mixed serrated and microtubular configurations had a regularly smooth luminal profile (p<0.05). Table III shows the comparison between the luminal profiles in sections and the degree of epithelial neoplasia. The results indicate that 89% (24/27) of the adenomas with carcinoma according to the Vienna classification (6) corresponded to sections having an asymmetrically lumpy profile, but only 11% (3/27) of those with a regularly smooth luminal profile had carcinoma according to the Vienna classification (6) (p<0.05). Discussion The results of this investigation demonstrated that the luminal profile of tissue sections from colorectal adenomas can be divided into two main groups: one with a regularly smooth profile and the other displaying an asymmetrically lumpy profile. The study was carried out keeping the H&E profile of the sections unchanged. However, various backgrounds were tested to enhance that profile. 3556

3 Rubio: Luminal Histological Outline and Colonic Adenoma Phenotypes Figure 2. Sections from an adenoma measuring 21 mm in the largest diameter, showing an asymmetrically lumpy luminal profile (enlargement of natural size). Sections in adenomas with asymmetrically lumpy profiles were significantly larger than in adenomas with regularly smooth profiles (96% vs. 4%, respectively, Table I; p<0.05), had more villous, villo-tubular, serrated or microtubular configurations than adenomas with regularly smooth profiles (72% vs. 28%, respectively, Table II; p<0.05), and harbored more carcinomas according to the Vienna classification (6) than adenomas with regularly smooth profiles (89% vs. 11%, respectively, Table III; p<0.05). Although the causes for the larger size, for the specific phenotypic histological configuration and for the more severe neoplastic change in adenomas with asymmetrically lumpy profiles than in those with regularly smooth profiles are not fully understood, it is not inconceivable that these parameters are closely related to the presence of irregular epithelial lumps in adenomas. These irregular epithelial lumps might represent foci of asymmetric epithelial outgrowth, budding asynchronically, apparently at a different pace. The lack of an organized growth control would imply that each lump of transformed epithelial cells Table I. The luminal profile and the size of the largest section in 107 colorectal adenomas. Size (mm) Regularly smooth Asymetrically lumpy 5 4 (11.8%) 3 (4.1%) (52.9%) 23 (31.5%) (32.3%) 25 (34.2%) (2.9%) 15 (20.5%) (6.8%) (1.4%) (1.4%) might be growing autonomously, at different speeds. Although the different pace of epithelial growth in adenomas is difficult to illustrate using proliferation markers such as Ki-67, clone MIB1, as all neoplastic cells in 3557

4 Figure 3. Section from an adenoma measuring 18 mm in the largest diameter, showing an asymmetrically lumpy luminal profile. Note an area with p53 mutation at arrow (enlargement of natural size). Table II. The luminal profile and the histological phenotype in 107 colorectal adenomas. Histological Regularly smooth Asymetrically lumpy phenotype Tubular 19 (55.9%) 36 (49.3%) Villous 15 (44.1%) 22 (30.1%) Mixed villotubular 0 10 (13.9%) Serrated 0 3 (4.1%) Microtubular 0 2 (2.7%) Combined 0 2 (2.7%) villous-serrated Table III. The luminal profile and the degree of neoplastic change according to the Vienna classification* (6) in 107 colorectal adenomas. Degree of Regularly smooth Asymetrically lumpy neoplasia* Low-grade dysplasia 21 (61.8%) 28 (38.4%) High-grade dysplasia 10 (29.4%) 21 (28.8%) Cancer in situ 0 8 (10.9%) Suspicion invasion 0 3 (4.1%) Intramucosal carcinoma 2 (2.9%) 6 (8.2%) Submucosal carcinoma 1 (1.4%) 7 (9.5%) 3558

5 Rubio: Luminal Histological Outline and Colonic Adenoma Phenotypes an adenoma are rapidly proliferating (6), preliminary observations with another immunostain, namely p53, showed the occurrence of mutated cells in one (Figure 3) or more foci within asymmetrical lumps. In conclusion, we demonstrated that sections from colonic adenomas display two different luminal profiles, one being regularly smooth and the other asymmetrically lumpy. Adenomas with the latter profile were larger, had more villous, serrated and microtubular configurations and more severe cellular changes than those with regularly smooth profiles. Studies have been initiated to clinically explore whether the luminal configuration of colonic adenomas can be of help in predicting, before endoscopical removal, accepted histological parameters. 3 Jackman R and Mayo C: The adenoma-carcinoma sequence in cancer of the colon. Surg Gynecol Obstet 93: , Muto T, Bussey H and Morson BC: The evolution of cancer of the colon and rectum. Cancer 36: , Rubio CA: Colorectal adenomas: time for reappraisal. Pathol Res Pract 198: , Rubio CA: Neoplasias of the colorectal crypts. Anticancer Res 25: , Rubio CA, G Nesi G, L Messerini L and Zampi GC: Serrated and microtubular colorectal adenomas in Italian patients. A 5-year survey. Anticancer Res 25: , Rubio CA, Nesi G, Messerini L, Mandai K, Itabashi M and Takubo K: The Vienna classification applied to colorectal adenomas. J Gastroenterology Hepatol 21: , References 1 Mentzel D: De excrentiis verracosocristasis. Acta Med Berlin 9: 78, Cited by Bacon HE (ed.). J Int Coll Surg 28: , Cripps WH: Two cases of disseminated polyps of the rectum. Trans Pathol Soc London 33: , Received March 12, 2007 Revised May 30, 2007 Accepted June 1,