Difference in Cell Proliferation between Two Structurally Different Lesions in Colorectal Adenomas: High-grade Dysplasia and Carcinoma In Situ

Background: Despite the fact that most Western pathologists diagnose carcinoma in situ (CIS) in many organs the same pathologists generally diagnose similar histological aberrations in colorectal adenomas, as high-grade dysplasia (HGD). Materials and Methods: Five large colorectal adenomas (measuring ≥20 mm) having areas of both HGD and CIS on staining with hematoxylin and eosin (H&E) were assessed with the proliferation antibody Ki-67 (clone MIB1). Results: HGD is built of tightly packed, spindle shaped, hyperchromatic cells with moderate pleomorphic nuclei having coarse chromatin and CIS of marked pleomorphic, vesicular, hypochromatic nuclei with a prominent nucleolus. Ki-67 was expressed in 96% of the HGD cells but only in 3.5% of the CIS cells (p<0.05). Conclusion: The results of this and of previous investigations using the DNA-specific Feulgen stain, suggest that HGD and CIS in colorectal adenomas are two dissimilar morphological entities with dissimilar molecular behaviour. HGD cells in colorectal adenomas seem to be proliferating at any given time, whereas the majority of the CIS cells are not. Despite most Western pathologists recognize carcinoma in situ (CIS) in many organs such as the breast, uterine cervix, skin, vulva, vagina, anus, testis, pancreas, extrahepatic bile ducts and the urinary bladder (1-11), the same pathologists generally diagnose similar histological aberrations in colorectal adenomas, as high-grade dysplasia (HGD). In the middle of the last century it was proposed that the term carcinoma in situ should be banned from the diagnostic terminology in colorectal adenomas as it could lead to misinterpretation by surgeons and to unnecessary surgical interventions (12-13). This maybe the reason why most Western pathologists continue to regard colorectal adenomas with HGD or with CIS, as synonymous. Nearly 10 years ago, a group of Western and Asian pathologists gathered in Vienna (14) to discuss the nomenclature for gastrointestinal intraepithelial neoplasias (i.e. non-invasive intraepithelial neoplasias) and of neoplasias with invasion. The final consensus reached there was that intraepithelial neoplasias in the GI tract should be sub-classified into low-grade dysplasia (LGD), HGD and CIS. Despite a consensus being reached by both schools, the histological criteria necessary to diagnose each of these lesions were not clearly defined, thus postponing the opportunity for its worldwide acceptance. More recently, the histological criteria for classification of the various categories proposed in Vienna were described for colorectal adenomas (15): of the 1552 adenomas studied, 591 (38.1%) had LGD (51.9%), 806 had HGD and 31 (2.0%) CIS. More recently, while studying sections from colorectal adenomas using Feulgen stain (16, 17) (used to specifically identify DNA material in cell specimens), we found that the nuclei of HGD cells were intense stained, whereas the nuclei in CIS cells often remained unstained. In the present work this phenomenon was further investigated by studying the pattern of cell proliferation in areas with HGD and with CIS in colorectal adenomas.