Three‐dimensional Reconstruction and Fractal Geometric Analysis of Serrated Adenoma

Abstract

Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34 ± ± ± ±0.08 for SA, 1.23 ± ± ± ±0.07 for TA, and 1.28 ± ± ± ±0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.

Serrated mucosal lesions of the colorectum

“…In the original work, 37% of serrated adenomas examined had elements of significant dysplasia, while 11% had intramucosal carcinoma [18], although other studies have noted significantly less high-grade dysplasia/intramucosal carcinoma [21]. The size of the serrated adenomas may speak to the propensity for malignant potential as only 1.5% of serrated adenomas smaller than 10 mm had concomitant carcinoma compared to 10% of those of 10 mm or more [22]. Nevertheless, accurate epidemiologic characterization of this entity is ultimately going to depend on consensus in the definition of a serrated adenoma before significant predictions about prevalence, natural history and outcomes assessment can be made.…”

Hyperplastic-like Colon Polyps That Preceded Microsatellite-Unstable Adenocarcinomas

“…Affected basilar crypt epithelial cells in serrated adenomas proliferate and grow outward rather than upward toward the luminal surface and at a pace that is greater than admixed, normal epithelial cells and the accompanying crypt-related stroma. 115 Expansion by these aberrantly growing cells seems to be facilitated by decreased apoptosis, which leads to decreased surface epithelial cell loss (anoikis). 39,116 Outward proliferation without migration may be the cause of basilar crypt dilation and inverted crypt growth in serrated adenomas.…”

Serrated Adenoma of the Colorectum Undergoes a Proliferation versus Differentiation Process: New Conceptual Interpretation of Morphogenesis

“…In addition, a three-dimensional reconstruction study of SA showed that Ki-67-positive cells were mainly aggregated in the concave sites of serrated glands; the authors hypothesized that the epithelia do not grow along the axis of the crypt, but perpendicularly to the axis, and this abnormal direction of epithelial growth may cause the characteristic serration in SA [17]. In our theory, the unique serrated figure is associated with terminal differentiation of cryptal cells because the tall projecting cells are positive for terminal differentiation markers such as CK20 and CAI.…”