Quantitative electron microscopic study on grades of atypia in adenomas of the human large bowel

Clarification of the ultrastructural features of the three different grades of histologic atypia of adenomas (i.e., mild, moderate, and severe atypia) with reference to carcinoma of the human colon and rectum was undertaken using electron microscopic quantitative analysis. Ten normal epithelia, 36 adenomas (14 with mild atypia, 13 with moderate atypia, and 9 with severe atypia) and 14 carcinomas (well-differentiated adenocarcinoma) were examined with light and electron microscopes. Although it has been generally accepted that malignant transformation of an adenoma gradually proceeds with increasing atypia, using light microscopy, ultrastructural quantitative analysis clearly revealed that fine features of individual atypia did not correspond with histologic grades of atypia. Ultrastructural changes occurred abruptly in moderate atypia and showed similar cellular characteristics to carcinoma cells. Mild atypia was almost similar in appearance to normal epithelial cells. Striking changes in the moderate atypic cells were plane apposition of the cell membrane, decrease of the desmosomes, and increase of the lysosomes. These atypical cells were assumed to play a significant role in the adenoma-carcinoma sequence. Therefore, radical surgical therapy would be required for moderate atypic adenoma of the large bowel that is difficult to remove endoscopically.